rainbow babies and children’s hospital, cleveland, oh 216 ... services...saad, u gergis, l...

Not for publication or presentation

A G E N D A CIBMTR WORKING COMMITTEE FOR HEALTH SERVICES AND INTERNATIONAL STUDIES Salt Lake City, UT Saturday, February 24, 2018, 2:45 – 4:45 PM

Co-Chair: Jignesh Dalal, MD; Rainbow Babies and Children’s Hospital, Cleveland, OH; Telephone: 216-983-1027; E-mail: [email protected]

Co-Chair: Theresa Hahn, PhD, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Telephone: 716-845-5819; E-mail: [email protected]

Co-Chair: Nandita Khera, MD, Mayo Clinic Arizona, Phoenix, AZ; Telephone: 480-342-0195; Email: [email protected]

Co-Chair: William Wood, MD, MPH, University of North Carolina, Chapel Hill, NC; Telephone: 919-843-6517; E-mail: [email protected]

Scientific Director: Wael Saber, MD, MS, CIBMTR Statistical Center; Telephone: 414-805-0677; Email: [email protected]

Statistical Director: Ruta Brazauskas, PhD, CIBMTR Statistical Center; Telephone: 414-955-8687; E-mail: [email protected]

Statistician: Naya He, MPH, CIBMTR Statistical Center; Telephone: 414-805-0685; E-mail: [email protected]

1. Introductiona. Minutes and Overview Plan from February 2017 meeting (Attachment 1)b. Instructions for sign-in and voting

2. Accrual summary (Attachment 2)

3. Presentations, published or submitted papers

a. HS13-01 A El-Jawahri, Y-B Chen, R Brazauskas, N He, S J. Lee, J Knight, N Majhail, D Buchbinder, R M. Schears, B M. Wirk, W A. Wood, I Ahmed, M Aljurf, J Szer, S M. Beattie, M Battiwalla, C Dandoy, M-Angel Diaz, A D’Souza, C O. Freytes, J Gajewski, U Gergis, S K. Hashmi, A Jakubowski, R T. Kamble, T Kindwall-Keller, H M. Lazarus, A K. Malone, D I. Marks, K Meehan, B N. Savani, R F. Olsson, D Rizzieri, A Steinberg, D Speckhart, D Szwajcer, H Schoemans, S Seo, C Ustun, Y Atsuta, J Dalal, C Sales-Bonfim, N Khera, T Hahn, W Saber. The Impact of pre-transplant depression on the outcomes of allogeneic and autologous hematopoietic stem cell transplantation. Cancer. 2017 Jan 19. doi: 10.1002

b. HS13-02 SD. Arnold, R Brazauskas, N He, Y Li, R Aplenc, Z Jin, M Hall, Y Atsuta, J Dalal, T Hahn, N Khera, C Bonfim, N S. Majhail, M Angel Diaz, C O. Freytes, W A. Wood, B M. Savani, R T. Kamble, S Parsons, I Ahmed, K Sullivan, S Beattie, C Dandoy, R Munker, S Marino, M Bitan, H Abdel-Azim, M Aljurf, R F. Olsson, S Joshi, D Buchbinder, M J. Eckrich, S Hashmi, H Lazarus, D I. Marks, A Steinberg, A Saad, U Gergis, L Krishnamurti, A Abraham, H G. Rangarajan, M Walters, J Lipscomb, W Saber, P Satwani. Clinical Risks and Healthcare Utilization of Hematopoietic Cell Transplantation for Sickle Cell Disease in the U.S. Using Merged Databases. Haematologica. 2017 Nov;102(11):1823-1832. doi: 10.3324

mailto:[email protected]

https://www.ncbi.nlm.nih.gov/pubmed/28102896

https://www.ncbi.nlm.nih.gov/pubmed/?term=.+Clinical+Risks+and+Healthcare+Utilization+of+Hematopoietic+Cell+Transplantation+for+Sickle+Cell+Disease+in+the+U.S.+Using+Merged+Databases


c. IS10-01 W Allen Wood, R Brazauskas, Zhen-H Hu, H Abdel-Azim, I A Ahmed, M Aljurf, S Badawy, ABeitinjaneh, G Biju, D Buchbinder, J Cerny, L Dedeken, M Diaz-Perez, C Freytes, S Ganguly, U Gergis, DG. Almaguer, A Gupta, G Hale, S K Hashmi, Y Inamoto, R T Kamble, A Kehinde, T Kindwall-Keller, JKnight, L Kumar, Y Kuwatsuka, J Law, H Lazarus, C LeMaistre, R Olsson, M Pulsipher, B N Savani, K RSchultz, A A Saad, M Seftel, S Seo, T C Shea, A Steinberg, K Sullivan, D Szwajcer, B Wirk, J Yared, AYong, J Dalal, T Hahn, N Khera, C Sales-Bonfim, Y Atsuta, W Saber. Country-level MacroeconomicIndicators predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in AcuteLymphoblastic Leukemia: A CIBMTR Analysis. Submitted.

4. Studies in progress (Attachment 3)a. HS12-02 Rates of Transplantation in Urban vs Rural Patients: Are Rural Patients Less Likely to Receive

an Allogeneic Transplant? (K Paulson/ M Seftel/ D Szwajcer) Manuscript preparationb. HS14-01 Investigating clinical outcomes and inpatient health care resource utilization of

hematopoietic cell transplantation for children with acute leukemia (S Arnold/ R Aplenc/M Pulsipher/P Satwani) Manuscript preparation

c. HS15-01 Who is lost to follow-up in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry? (D Buchbinder/T Hahn/K Ballen/ W Saber/ S Parsons) Analysis

d. HS15-02 Impact of socioeconomic status on pediatric stem cell transplant outcomes (K Bona/ J Wolfe/C Duncan/ L Lehmann) Data file preparation

e. HS16-01 Trends in Utilization and Outcomes of Autologous and Allogeneic Hematopoietic cell Transplantation in Racial and Ethnic Minorities (N Khera/ T Hahn/ S Ailawadhi / W Saber) Protocol Development

f. HS16-02: The Impact of Marital Status on Hematopoietic Stem Cell Transplant Recipient Outcomes: A surrogate for consistent caregiver (S M Beattie/ J Tay/ C Bredeson) Data file preparation

g. HS16-03 Relationship of Race/Ethnicity and Survival after Single and Double Umbilical Cord Blood Transplantation (K Ballen) Protocol Development

h. HS17-01 Association of community health status and center survival for allogeneic hematopoietic cell transplantation (S Hong/ N Singh Majhail) Protocol Development

5. Future/proposed studiesa. PROP 1707-02 Patient outcomes in the first five years after centers initiate alternative donor

hematopoietic cell transplant programs for hematologic malignancy (Mary-Elizabeth Muchmore Percival/William Allen Wood) (Attachment 4)

b. PROP 1711-26 International collaborative study to compare the prognosis for acute leukemia patients transplanted with intensified myeloablative regimens (Yasuyuki Arai/Yoshiko Atsuta/ShingoYano/Shinichi Kako) (Attachment 5)

c. PROP 1711-27 Fludarabine/busulfan versus fludarabine/melphalan conditioning in patients with acute lymphoblastic leukemia; An international collaborative study of cohorts from the US and Japan(Yasuyuki Arai/Yoshiko Atsuta/Shinichi Kako/Koji Kawamura) (Attachment 6)

d. PROP 1711-43 Racial differences in long term survivor outcomes after Allogeneic hematopoietic cell transplantation (Brandon J. Blue/Navneet Majhail) (Attachment 7)


e. PROP 1711-109 Racial/ethnic disparities in receipt of hematopoietic cell transplantation and subsequent resource utilization in children with acute leukemia (Lena Winestone/ Richard Aplenc/Kelly Getz) (Attachment 8)

f. PROP 1711-113 Do patient outcomes following hematopoietic cell transplantation vary in the time period before and immediately after introduction of an electronic health record? (Mary-Elizabeth Muchmore Percival/ William Allen Wood) (Attachment 9)

g. PROP 1711-130 Race, ethnicity and outcomes of allogeneic stem cell transplantation for acute lymphoblastic leukemia in Hispanic patients (Anne S. Renteria/ Luis Isola/ Nina A. Bickell) (Attachment 10)

Dropped proposed studies a. PROP 1706-01 Deconstructing the Biological Impact of Race on Outcomes after Myeloablative

Conditioning and Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Leukemia.Dropped due to overlapped with previous studies.

b. PROP 1711-54 Trends and cost prediction in pediatric allogeneic hematopoietic cell transplant.Dropped due to overlapped with previous studies.

c. PROP 1711-58 Exploring the Transplant Center Volume-Outcomes relationship in acute leukemias.Dropped due to overlapped with previous studies.

d. PROP 1711-87 Bone Marrow Transplant Utilization and Survival Outcomes among Adults byAppalachian and Non-Appalachian Areas of the United States. Dropped due to overlapped withprevious studies.

e. PROP 1711-110 Effect of race on outcomes following HLA- haploidentical transplant with post-transplant Cytoxan for hematological malignancies. Dropped due to small sample size.

6. Other Business

Not for publication or presentation Attachment 1

MINUTES AND OVERVIEW PLAN CIBMTR WORKING COMMITTEE FOR HEALTH SERVICES AND INTERNATIONAL STUDIES Orlando, Florida Friday, February 24, 2017, 12:15 – 2:15 PM

Co-Chair: Jignesh Dalal, MD; Rainbow Babies and Children’s Hospital, Cleveland, OH; Telephone: 216-983-1027; E-mail: [email protected]

Co-Chair: Theresa Hahn, PhD, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Telephone: 716-845-5819; E-mail: [email protected]

Co-Chair: Nandita Khera, MD, Mayo Clinic Arizona, Phoenix, AZ; Telephone: 480-342-0195; Email: [email protected]

Co-Chair: Carmem Sales-Bonfim, MD, Hospital de Clinicas – UFPR, Curitiba, Brazil; Telephone: 55-41-3360-1000; E-mail: [email protected]

Scientific Director: Wael Saber, MD, MS, CIBMTR Statistical Center; Telephone: 414-805-0677; Email: [email protected]

Statistical Director: Ruta Brazauskas, PhD, CIBMTR Statistical Center; Telephone: 414-955-8687; E-mail: [email protected]

Statistician: Naya He, MPH, CIBMTR Statistical Center; Telephone: 414-805-0685; E-mail: [email protected]

1. Introductiona. Minutes and Overview Plan from February 2016 meeting (Attachment 1)b. Instructions for sign-in and voting

The meeting was called to order at 12:15pm by Dr. Jignesh Dalal. He described the goals, expectations, and limitations of the committee, and he gave an introduction of the data that are collected in CRF and TED database. He also explained the voting process, role of working committee members, rules of authorship and statistical hour allocation, and importance of the conference evaluations.

Dr. Jignesh Dalal announced that Dr. William Wood has been appointed as the co-Chair of the Health Services and International Studies Working Committee starting March 1st. Meanwhile, Dr. Carmem Sales-Bonfim will be completing her 5-year term as co-Chair at the end of this month. On behalf of the committee, Dr. Saber thanked Dr. Carmem Sales-Bonfim for her leadership and service to the committee.

The minutes of the February 2016 meeting were approved without modifications.


Not for publication or presentation Attachment 1 2. Accrual summary (Attachment 2)

Due to the full agenda, the accrual summary of registration and research cases between 2008 and 2016 were not presented to the committee but were available as part of the Working Committee attachments.

3. Presentations, published or submitted papers

Due to the full agenda, the 2016 presentations and published papers were mentioned, but not presented. Two papers were published, one submitted, and two ASH presentations were given during the past year.

a. HS07-02b EM Denzen, V Thao , T Hahn, SJ Lee, PL McCarthy, JD Rizzo, M Ammi, R Drexler, S Flesch, H James, N Omondi, E Murphy, K Pederson, NS Majhail. Financial impact of allogeneic hematopoietic cell transplantation on patients and families over 2 years: results from a multicenter pilot study. Bone Marrow Transplant. 2016 Sep;51(9):1233-40. doi: 10.1038 https://www.cibmtr.org/ReferenceCenter/Patient/PatientSummaries/Documents/2016.04.18%20Denzen.pdf

b. HS13-01 A El-Jawahri, Y-B Chen, R Brazauskas, N He, S J. Lee, J Knight, N Majhail, D Buchbinder, R M. Schears, B M. Wirk, W A. Wood, I Ahmed, M Aljurf, J Szer, S M. Beattie, M Battiwalla, C Dandoy, M-Angel Diaz, A D’Souza, C O. Freytes, J Gajewski, U Gergis, S K. Hashmi, A Jakubowski, R T. Kamble, T Kindwall-Keller, H M. Lazarus, A K. Malone, D I. Marks, K Meehan, B N. Savani, R F. Olsson, D Rizzieri, A Steinberg, D Speckhart, D Szwajcer, H Schoemans, S Seo, C Ustun, Y Atsuta, J Dalal, C Sales-Bonfim, N Khera, T Hahn, W Saber. The Impact of pre-transplant depression on the outcomes of allogeneic and autologous hematopoietic stem cell transplantation. Cancer. 2017 Jan 19. doi: 10.1002

c. HS13-02 SD. Arnold, R Brazauskas, N He, Y Li, R Aplenc, Z Jin, M Hall, Y Atsuta, J Dalal, T Hahn, N Khera, C Bonfim, N S. Majhail, M Angel Diaz, C O. Freytes, W A. Wood, B M. Savani, R T. Kamble, S Parsons, I Ahmed, K Sullivan, S Beattie, C Dandoy, R Munker, S Marino, M Bitan, H Abdel-Azim, M Aljurf, R F. Olsson, S Joshi, D Buchbinder, M J. Eckrich, S Hashmi, H Lazarus, D I. Marks, A Steinberg, A Saad, U Gergis, L Krishnamurti, A Abraham, H G. Rangarajan, M Walters, J Lipscomb, W Saber, P Satwani. Clinical Risks and Healthcare Utilization of Hematopoietic Cell Transplantation for Sickle Cell Disease in the U.S. Using Merged Databases. Submitted.

d. HS12-02 K Paulson, R Brazauskas, N He, D Szwajcer , M Seftel, Y Atsuta, J D Dalal, T Hahn, C Bonfim, N Khera, L Burns, L Mau, N Majhail, W Saber. Inferior Access to Allogeneic Transplant in Disadvantaged Populations: A CIBMTR Analysis. Oral presentation at ASH in San Diego, CA, December 2016

e. HS14-01 S D. Arnold, R Brazauskas, N He, Y Li, P Satwani, M A. Pulsiphe, M Hall, Y Atsuta, MD ,J D Dalal, T Hahn, C Bonfim, N Khera, R Aplenc, Wl Saber. Role of donor source on clinical outcomes and inpatient resource utilization for hematopoietic cell transplantation in children with acute leukemia. Poster presentation at ASH in San Diego, CA, December 2016

4. Studies in progress (Attachment 3) The progress of the ongoing studies during the past year was not presented in order to provide reasonable time to the new proposals for presentation and discussion. A summary of the progress was provided as an attachment to the committee members.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Financial+impact+of+allogeneic+hematopoietic+cell+transplantation+on+patients+and+families+over+2+years%3A+results+from+a+multicenter+pilot+study.

https://www.ncbi.nlm.nih.gov/pubmed/28102896

Not for publication or presentation Attachment 1 a. HS12-02 Rates of Transplantation in Urban vs Rural Patients: Are Rural Patients Less Likely to Receive

an Allogeneic Transplant? (K Paulson/ M Seftel/ D Szwajcer) Analysis b. IS10-01 Outcomes of HCT for ALL: an international comparative analysis (W Wood) Manuscript

Preparation c. HS14-01 Investigating clinical outcomes and inpatient health care resource utilization of

hematopoietic cell transplantation for children with acute leukemia (S Arnold/ R Aplenc/M Pulsipher/P Satwani) Analysis

d. HS15-01 Who is lost to follow-up in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry? (D Buchbinder/ T Hahn/ K Ballen/ W Saber/ S Parsons) Protocol Development

e. HS15-02 Impact of socioeconomic status on pediatric stem cell transplant outcomes (K Bona/ J Wolfe/ C Duncan/ L Lehmann) Data file preparation

f. HS16-01 Trends in Utilization and Outcomes of Autologous and Allogeneic Hematopoietic cell Transplantation in Racial and Ethnic Minorities (N Khera/ T Hahn/ S Ailawadhi / W Saber) Protocol Development

g. HS16-02: The Impact of Marital Status on Hematopoietic Stem Cell Transplant Recipient Outcomes: A surrogate for consistent caregiver (S M Beattie/ J Tay/ C Bredeson) Protocol Development

h. HS16-03: Relationship of Race/Ethnicity and Survival after Single and Double Umbilical Cord Blood Transplantation (K Ballen) Protocol Development

5. Future/proposed studies Dr. Theresa Hahn led this session.

a. PROP 1608-04 Safety and cost-effectiveness of outpatient autologous stem cell transplantation: a multicenter retrospective case-control study using propensity score matching (N Dunavin/ A Abdallah/ S Ganguly) (Attachment 4) Dr. Dunavin presented this study. The specific aim of this study is to compare costs, health care utilization and safety of outpatient vs. inpatient autologous HCT for multiple myeloma. This will be accomplished by linking CIBMTR to Centers for Medicare and Medicaid Services (CMS) claims database, using billing codes to capture costs. One participant expressed concern regarding the ability of CMS database to capture outpatients to inpatients transition. Dr. Dunavin agreed this is a good point. He stated he would need to examine different coding patterns defining outpatients and inpatients. There were some discussions about the safety of outpatient and inpatient transplant and payer issues. Dr. Mau suggested using date of transplant as a key variable when merging two data base. Dr. Arnold and Dr. Mau suggested need for capturing supportive service since Medicare and Medicaid include patients on disability. This proposal was accepted by the working committee and leadership.

b. PROP 1611-73 Association of community health status and center survival for allogeneic hematopoietic cell transplantation (S Hong/ N Singh Majhail / T Hahn) (Attachment 5) Dr. Hong presented this study. The specific aim of this study is using the latest CIBMTR center specific outcomes dataset, evaluate association between social determinants of health for community where patients reside (assessed by County Health Rankings based on zip code of patient residence) and patient 1-year overall survival after allogeneic HCT. In responding to a participant questioning how to account for patients come from one county go to different centers, Dr. Hong replied this study will look at how the community factor which is the patient’s residence influences the transplant outcome and compare with where is the transplant center located. There were some discussions on the implication of the study. Participants and Dr. Saber noted that there are some factors that centers could not change, but if this study finds some urgent community factors that centers could change


then we could use to guide center’s practice. One participant noted concern how to adjust patient moving from one center to another center, Dr. Hong respondent that it needs further discussion if the proposal is accepted. There were discussions about the SES information that are collected in the CIBMTR forms. Unfortunately these data are limited. This proposal was accepted by the working committee and leadership.

c. PROP 1611-104 Comparing Outcomes with Bone Marrow and Peripheral Blood Stem Cells for Matched Sibling Transplants in Patients with Beta-Thalassemia Major across Different Economic Region (A O. Gupta/ J Dalal/ R Kumar) (Attachment 6) Dr. Gupta presented this study. The specific aims of this study are two-fold: 1. To assess difference in outcomes in HSCT using PBSCs versus BM stem cells for beta thalassemia major across various economic regions. 2. To assess difference in outcomes in HSCT with different conditioning regimens, using PBSCs versus BM stem cells across various economic regions for beta thalassemia. Dr. Saber expressed concern about the differential of completeness of data by graft source. And he suggested based on other international studies the end point of this study should not beyond one year. Dr. Hahn suggested limiting the population from 2000 and beyond since before 2000 there were only 30 patients in the peripheral blood stem cells group.

Dropped proposed studies a. PROP 1610-06 Relationship between volume and outcome in acute leukemia patients undergoing

allogeneic hematopoietic cell transplant. Dropped due to overlapped with an on-going study.

b. PROP 1610-07 Scheduling Elective Hematopoietic Stem Cell Transplantation-Does Avoiding Admission During the Winter Season Impact Transplant Related Mortality? Dropped due to insufficient sample size.

c. PROP 1611-14 The effect of race and ethnicity on stem cell transplant utilization rates (STUR) and outcomes of autologous stem cell transplantation for diseases excluding multiple myeloma. Dropped due to overlapped with an on-going study.

d. PROP 1611-90 Haplo-identical hematpoietic stem cell clinical experience and outcome in hematologic malignancies across different economic and regional boundaries. Dropped due to insufficient sample size.

e. PROP 1611-145 Deconstructing the Impact of Race on Outcomes after Myeloablative Conditioning and Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Leukemia. Dropped due to overlapped with an on-going study.

f. PROP 1611-157 Effects of Socioeconomic status and Race/Ethnicity on Survival after Reduced Intensity Conditioning Hematopoietic Cell Transplantation in Acute Leukemia. Dropped due to insufficient sample size.

6. Other Business a. IS10-01 analysis result update and quality issue of international centers (W Wood C Sales-Bonfim)

Dr. Wood presented the analysis result of IS10-01 and discussed the limitation of this study. Dr. Carmem Sales-Bonfim using two studies as examples discussed the challenges when CIBMTR doing international studies. She suggested removing items from the TED forms that are not relevant to a specific region and translate manuals for other non-English speaking country users.

Not for publication or presentation Attachment 1 b. Health Services Research Program Updates(E Denzen)

Dr. Denzen gave a brief introduction of current ongoing studies in the health service research program.

Dr. Saber adjourned the meeting at 2:10pm.


Working Committee Overview Plan for 2017-2018

a. IS10-01 Outcomes of HCT for ALL: an international comparative analysis - We anticipate a submitted manuscript by June 2017. 40 statistical hours have been allocated to accomplish this goal.

b.

HS12-02 Rates of Transplantation in Urban vs Rural Patients: Are Rural Patients Less Likely to Receive an Allogeneic Transplant? - We anticipate a submitted manuscript by June 2017. No statistical hours have been allocated to accomplish this goal.

c. HS13-02 Health care utilization of HCT in children with sickle cell disease- We anticipate having the manuscript published by June 2017. No statistical hours have been allocated to accomplish this goal.

d. HS14-01 Investigating clinical outcomes and inpatient health care resource utilization of hematopoietic cell transplantation for children with acute leukemia- We anticipate a submitted manuscript by June 2017. 100 statistical hours have been allocated to accomplish this goal.

e. HS15-01 Who is lost to follow-up in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry? - We anticipate having this study in manuscript preparation by June 2017. After circulating to the Writing Committee for feedback, we expect to submit the final manuscript by June 2018. 280 statistical hours have been allocated to accomplish these goals.

f. HS15-02 Impact of Socioeconomic Status on Pediatric Stem Cell Transplant Outcomes – We anticipate having this study in analysis by June 2017. After circulating to the Writing Committee for feedback, we expect to submit the final manuscript by June 2018. 260 statistical hours have been allocated to accomplish these goals.

g.

HS16-01 Trends in Utilization and Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Racial and Ethnic Minorities – We anticipate having the protocol finalized by June 2017. We further anticipate preparing the data file by June 2018. 160 statistical hours have been allocated to accomplish these goals.

h. HS16-02 The Impact of Marital Status on Hematopoietic Stem Cell Transplant Recipient Outcomes: A surrogate for consistent caregiver - We anticipate having the protocol finalized by June 2017. We further anticipate preparing the data file by June 2018. 160 statistical hours have been allocated to accomplish these goals.

i. HS16-03 Relationship of Race/Ethnicity and Survival after Single and Double Umbilical Cord Blood Transplantation - We anticipate having the protocol finalized by June 2017. We further anticipate preparing the data file by June 2018. 160 statistical hours have been allocated to accomplish these goals.

Oversight Assignments for Working Committee Leadership (March 2017) Theresa Hahn HS15-01 Who is lost to follow-up in the Center for International Blood and Marrow

Transplant Research (CIBMTR) registry?

HS15-02 Impact of Socioeconomic Status on Pediatric Stem Cell Transplant Outcomes

HS17-01 Association of community health status and center survival for allogeneic hematopoietic cell transplantation

Jignesh Dalal HS14-01: Investigating clinical outcomes and inpatient health care resource utilization of hematopoietic cell transplantation for children with acute leukemia

Not for publication or presentation Attachment 1 HS13-02: Health care utilization of for children with sickle cell disease

William Wood IS10-01: Outcomes of HCT for ALL: an international comparative analysis

HS16-03 Relationship of race/ethnicity and survival after single and double umbilical cord blood transplantation

Nandita Khera HS16-01 Trends in utilization and outcomes of autologous and allogeneic hematopoietic cell transplantation in racial and ethnic minorities

HS16-02 The impact of marital status on hematopoietic stem cell transplant recipient outcomes: a surrogate for consistent caregiver


Accrual Summary for the Health Services and International Studies Working Committee

Table 1. Characteristics of recipients who underwent a first allogeneic transplant registered with the CIBMTR

Variable TED N (%) CRF N (%) Number of patients 229140 99558 Number of centers 635 562 Age at transplant, years

Median 36 (<1-88) 32 (<1-83) 0-9 32870 (14) 16973 (17) 10-19 29713 (13) 14890 (15) 20-29 31034 (14) 14584 (15) 30-39 34569 (15) 15558 (16) 40-49 38814 (17) 15556 (16) 50-59 36308 (16) 12831 (13) 60-69 22877 (10) 7936 (8) 70+ 2947 (1) 1230 (1) Missing 8 (<1) 0

Recipient gender Male 134139 (59) 58412 (59) Female 94734 (41) 41141 (41) Missing 267 (<1) 5 (<1)

Recipient race Caucasian 155000 (68) 79881 (80) African-American 10536 (5) 5472 (5) Asian 17678 (8) 7910 (8) Pacific islander 420 (<1) 190 (<1) Native American 660 (<1) 332 (<1) Other 8473 (4) 3943 (4) Unknown 36373 (16) 1830 (2)

Disease Acute myelogenous leukemia 71443 (31) 28181 (28) Acute lymphoblastic leukemia 39404 (17) 16706 (17) Other leukemia 5950 (3) 2207 (2) Chronic myelogenous leukemia 28953 (13) 14878 (15) Myelodysplastic/myeloproliferative disorders 25942 (11) 11509 (12) Other acute leukemia 2497 (1) 956 (<1) Non-Hodgkin lymphoma 15985 (7) 5811 (6) Hodgkin lymphoma 1523 (<1) 525 (<1) Plasma cell disorder/Multiple Myeloma 3349 (1) 1356 (1)


Variable TED N (%) CRF N (%) Other Malignancies 1179 (<1) 500 (<1) Breast Cancer 183 (<1) 92 (<1) Severe aplastic anemia 13297 (6) 6858 (7) Inherited abnormalities erythrocyte differentiation or function 8987 (4) 4723 (5) SCID and other immune system disorders 5701 (2) 2852 (3) Inherited abnormalities of platelets 200 (<1) 101 (<1) Inherited disorders of metabolism 2557 (1) 1478 (1) Histiocytic disorders 1508 (<1) 704 (<1) Autoimmune Diseases 112 (<1) 44 (<1) Other diseases 370 (<1) 77 (<1) Year of transplant <1985 4898 (2) 4506 (5) 1985-1989 10638 (5) 9499 (10) 1990-1994 22984 (10) 14746 (15) 1995-1999 36164 (16) 16798 (17) 2000-2004 41090 (18) 17089 (17) 2005-2009 40760 (18) 17886 (18) 2010-2014 47729 (21) 11399 (11) 2015-2017 24877 (11) 7635 (8) Education No primary education NA 40 (<1) Less than primary or elementary education 62 (<1) Primary of elementary education 669 (<1) Lower secondary education 606 (<1) Upper secondary education 9506 (10) Post-secondary, non-tertiary education 3673 (4) Tertiary education, Type A 6924 (7) Tertiary education, Type B 1438 (1) Advance research qualification 1859 (2) Age<18 years old 28787 (29) Missing 45994 (46) Health insurance No insurance NA 3509 (4) Medicaid 8156 (8) Medicare 4381 (4) Disability insurance 628 (<1) HMO 2499 (3) Private health insurance 18373 (18)


Variable TED N (%) CRF N (%) National health insurance 14959 (15) VA/Military 705 (<1) Other 3436 (3) Missing 42912 (43) Occupation Professional, technical, or related occupation NA 17592 (18) Manager, administrator or proprietor 3143 (3) Clerical or related occupation 2292 (2) Sales occupation 1730 (2) Service occupation 2556 (3) Skilled crafts or related occupation 2732 (3) Equipment/vehicle operator or related occupation 1211 (1) Laborer 1729 (2) Farmer 332 (<1) Member of military 271 (<1) Homemaker 1301 (1) Student 9376 (9) Under school age 2142 (2) Not previously employed 1711 (2) Other, specify 7597 (8) Missing 43843 (44) Annual income Less than $20,000 NA 323 (<1) $20,000 - $39,999 344 (<1) $40,000 - $59,999 276 (<1) $60,000 - $79,999 200 (<1) $80,000 and over 340 (<1) Recipient declines to provide this information 300 (<1) Age<18 years old 28787 (29) Missing 68988 (69)


Table 2. Characteristics of recipients who underwent a first autologous transplant registered with the CIBMTR

Variable TED N (%) CRF N (%) Number of patients 223041 42464 Number of centers 600 440 Age at transplant, years Median 52 (<1-86) 49 (<1-83) 0-9 9666 (4) 2211 (5) 10-19 7394 (3) 1700 (4) 20-29 15602 (7) 2989 (7) 30-39 24142 (11) 5563 (13) 40-49 42490 (19) 9656 (23) 50-59 61588 (28) 11175 (26) 60-69 51938 (23) 7879 (19) 70+ 10221 (5) 1291 (3) Recipient gender Male 118586 (53) 20394 (48) Female 104069 (47) 22063 (52) Missing 386 (<1) 7 (<1) Recipient race Caucasian 156037 (70) 34125 (80) African-American 19019 (9) 4537 (11) Asian 5443 (2) 1074 (3) Pacific islander 250 (<1) 38 (<1) Native American 568 (<1) 167 (<1) Other 5627 (3) 1441 (3) Unknown 36097 (16) 1082 (3) Disease Acute myelogenous leukemia 8278 (4) 2390 (6) Acute lymphoblastic leukemia 1603 (<1) 473 (1) Other leukemia 790 (<1) 248 (<1) Chronic myelogenous leukemia 715 (<1) 296 (<1) Myelodysplastic/myeloproliferative disorders 287 (<1) 92 (<1)

Other acute leukemia 151 (<1) 31 (<1) Non-Hodgkin lymphoma 61849 (28) 10270 (24) Hodgkin lymphoma 23604 (11) 3600 (8) Plasma cell disorder/Multiple Myeloma 83430 (37) 12844 (30) Other Malignancies 18270 (8) 4277 (10)


Variable TED N (%) CRF N (%) Breast Cancer 23011 (10) 7768 (18) Autoimmune Diseases 587 (<1) 126 (<1) Other diseases 466 (<1) 49 (<1) Year of transplant <1985 31 (<1) 5 (<1) 1985-1989 2093 (<1) 672 (2) 1990-1994 20184 (9) 7579 (18) 1995-1999 42102 (19) 13067 (31) 2000-2004 36640 (16) 6136 (14) 2005-2009 38886 (17) 7620 (18) 2010-2014 52660 (24) 4049 (10) 2015-2017 30445 (14) 3336 (8) Education No primary education NA 8 (<1) Less than primary or elementary education 33 (<1) Primary of elementary education 296 (<1) Lower secondary education 289 (<1) Upper secondary education 5742 (14) Post-secondary, non-tertiary education 2469 (6) Tertiary education, Type A 4767 (11) Tertiary education, Type B 951 (2) Advance research qualification 1562 (4) Age<18 years old 3437 (8) Missing 22910 (54) Health insurance No insurance NA 732 (2) Medicaid 3156 (7) Medicare 3550 (8) Disability insurance 348 (<1) HMO 2979 (7) Private health insurance 9226 (22) National health insurance 1721 (4) VA/Military 614 (1) Other 2150 (5) Missing 17988 (42) Occupation Professional, technical, or related occupation NA 16158 (38)

Manager, administrator or proprietor 1382 (3)


Variable TED N (%) CRF N (%) Clerical or related occupation 1048 (2) Sales occupation 696 (2) Service occupation 1244 (3) Skilled crafts or related occupation 1234 (3) Equipment/vehicle operator or related occupation 620 (1)

Laborer 842 (2) Farmer 172 (<1) Member of military 132 (<1) Homemaker 537 (1) Student 1024 (2) Under school age 338 (<1) Not previously employed 898 (2) Other, specify 3194 (8) Missing 12945 (30) Annual income Less than $20,000 NA 365 (<1) $20,000 - $39,999 365 (<1) $40,000 - $59,999 377 (<1) $60,000 - $79,999 217 (<1) $80,000 and over 461 (1) Recipient declines to provide this information 218 (<1)

Age<18 years old 3437 (8) Missing 37024 (87)


Table 3. Characteristics of recipients who received a first transplant from US centers reported to the CIBMTR, 2008 – 2017 (CRF)

Variable Allogeneic

N (%) Autologous

N (%) Number of patients 22202 10056 Number of centers 181 172 Patient age, median 50 (<1-82) 57 (<1-82) Education No primary education 15 (<1) 7 (<1) Less than primary or elementary education 34 (<1) 17 (<1) Primary of elementary education 85 (<1) 63 (<1) Lower secondary education 413 (2) 250 (2) Upper secondary education 4538 (20) 2578 (26) Post-secondary, non-tertiary education 1575 (7) 901 (9) Tertiary education, Type A 4190 (19) 2148 (21) Tertiary education, Type B 921 (4) 584 (6) Advance research qualification 767 (3) 382 (4) Age<18 years old 4496 (20) 605 (6) Missing 5168 (23) 2521 (25) Health insurance No insurance 398 (2) 151 (2) Medicaid 4550 (20) 1377 (14) Medicare 3506 (16) 2114 (21) Disability insurance 470 (2) 272 (3) Private health insurance 12035 (54) 5611 (56) National health insurance 112 (<1) 7 (<1) VA/Military 295 (1) 158 (2) Other 467 (2) 115 (1) Missing 369 (2) 251 (2) Occupation Professional, technical, or related occupation 4246 (19) 2250 (22) Manager, administrator or proprietor 1916 (9) 979 (10) Clerical or related occupation 1266 (6) 725 (7) Sales occupation 1012 (5) 475 (5) Service occupation 1498 (7) 917 (9) Skilled crafts or related occupation 1552 (7) 842 (8) Equipment/vehicle operator or related occupation 715 (3) 435 (4) Laborer 981 (4) 566 (6) Farmer 166 (<1) 98 (<1)


Variable Allogeneic

N (%) Autologous

N (%) Member of military 166 (<1) 99 (<1) Homemaker 520 (2) 265 (3) Student 3660 (16) 455 (5) Under school age 1350 (6) 268 (3) Not previously employed 440 (2) 236 (2) Other, specify 1042 (5) 401 (4) Missing 1672 (8) 1045 (10) Annual income Less than $20,000 181 (<1) 147 (1) $20,000 - $39,999 201 (<1) 148 (1) $40,000 - $59,999 154 (<1) 162 (2) $60,000 - $79,999 121 (<1) 104 (1) $80,000 and over 216 (<1) 188 (2) Recipient declines to provide this information 287 (1) 206 (2) Age<18 years old 4496 (20) 605 (6) Missing 16546 (75) 8496 (84)


Table 4. Characteristics of recipients who received allogeneic transplants registered with the CIBMTR by WHO region, 2008 – 2017(TED)

Variable Africa Latin

Americas US / Canada Eastern

Mediterranean Europe Southeastern

Asia Western

Pacific Number of patients 36 3064 63179 2801 12169 1268 6370 Number of centers 2 28 208 7 104 9 27 Age, in years <10 0 590 (19) 6836 (11) 1227 (44) 1042 (9) 384 (30) 787 (12) 10-19 6 (17) 597 (19) 5396 (9) 661 (24) 891 (7) 312 (25) 780 (12) 20-29 6 (17) 482 (16) 5391 (9) 468 (17) 1317 (11) 185 (15) 729 (11) 30-39 2 (6) 486 (16) 5583 (9) 240 (9) 1378 (11) 181 (14) 864 (14) 40-49 7 (19) 435 (14) 8590 (14) 149 (5) 2099 (17) 121 (10) 1165 (18) 50-59 9 (25) 338 (11) 14603 (23) 50 (2) 2751 (23) 80 (6) 1375 (22) 60-69 6 (17) 113 (4) 14469 (23) 6 (<1) 2407 (20) 5 (<1) 653 (10) ≥70 0 23 (<1) 2310 (4) 0 284 (2) 0 17 (<1) Missing 0 0 1 (<1) 0 0 0 0 Gender Male 26 (72) 1827 (60) 36464 (58) 1647 (59) 7148 (59) 851 (67) 3708 (58) Female 10 (28) 1237 (40) 26715 (42) 1154 (41) 5021 (41) 417 (33) 2662 (42) Primary disease AML 13 (36) 800 (26) 24337 (39) 518 (18) 4857 (40) 246 (19) 2516 (39) ALL 2 (6) 784 (26) 9920 (16) 490 (17) 2065 (17) 145 (11) 1362 (21) CML 3 (8) 214 (7) 2234 (4) 95 (3) 456 (4) 56 (4) 165 (3) Myelodysplastic disorders

7 (19) 313 (10) 10468 (17) 85 (3) 2121 (17) 83 (7) 945 (15)

NHL 3 (8) 62 (2) 5221 (8) 19 (<1) 630 (5) 28 (2) 240 (4)

Hodgkin lymphoma 0 17 (<1) 332 (<1) 3 (<1) 57 (<1) 6 (<1) 26 (<1) Multiple myeloma 0 1 (<1) 265 (<1) 8 (<1) 76 (<1) 1 (<1) 6 (<1) Other malignancies 1 (3) 78 (3) 3201 (5) 41 (1) 678 (6) 17 (1) 239 (4) Severe aplastic anemia 4 (11) 449 (15) 2338 (4) 353 (13) 453 (4) 222 (18) 500 (8) Other non-malignancies

3 (8) 346 (11) 4863 (8) 1189 (42) 776 (6) 464 (37) 371 (6)

Donor type HLA-identical sibling 15 (42) 1777 (58) 20102 (32) 2162 (77) 3991 (33) 860 (68) 2439 (38)

Other related donor 1 (3) 292 (10) 5991 (9) 343 (12) 629 (5) 229 (18) 763 (12) Unrelated donor 20 (56) 994 (32) 37049 (59) 296 (11) 6758 (56) 179 (14) 3165 (50)

Missing 0 1 (<1) 37 (<1) 0 791 (7) 0 3 (<1) Graft type Bone Marrow 1 (3) 1698 (55) 14242 (23) 1439 (51) 2702 (22) 112 (9) 1226 (19)


Variable Africa Latin

Americas US / Canada Eastern

Mediterranean Europe Southeastern

Asia Western

Pacific Peripheral Blood 34 (94) 1182 (39) 42405 (67) 1079 (39) 8950 (74) 1143 (90) 4574 (72) Cord Blood 1 (3) 183 (6) 6499 (10) 281 (10) 513 (4) 13 (1) 565 (9) Missing 0 1 (<1) 33 (<1) 2 (<1) 4 (<1) 0 5 (<1) Year of transplant 2008 5 (14) 188 (6) 5036 (8) 436 (16) 1599 (13) 56 (4) 491 (8) 2009 11 (31) 313 (10) 5590 (9) 460 (16) 1704 (14) 61 (5) 659 (10) 2010 8 (22) 385 (13) 5824 (9) 451 (16) 1692 (14) 44 (3) 758 (12) 2011 10 (28) 343 (11) 6347 (10) 220 (8) 1538 (13) 138 (11) 849 (13) 2012 1 (3) 409 (13) 6515 (10) 251 (9) 1533 (13) 145 (11) 799 (13) 2013 1 (3) 357 (12) 7021 (11) 209 (7) 1420 (12) 112 (9) 743 (12) 2014 0 305 (10) 7166 (11) 273 (10) 788 (6) 123 (10) 706 (11) 2015 0 304 (10) 7363 (12) 251 (9) 635 (5) 178 (14) 500 (8) 2016 0 295 (10) 7337 (12) 174 (6) 623 (5) 242 (19) 636 (10) 2017 0 165 (5) 4980 (8) 76 (3) 637 (5) 169 (13) 229 (4)


Table 5. Allogeneic transplant recipients and centers by country registered with the CIBMTR, 2008-2017(TED)

Regions N Centers

Africa

South Africa 36 2

Americas

USA 59752 193

Argentina 237 4

Brazil 2414 11

Canada 3427 15

Chile 5 2

Venezuela 49 2

Mexico 51 2

Uruguay 39 3

Peru 71 1

Columbia 198 3

Eastern Mediterranean

Saudi Arabia 1685 2

Egypt 19 2

Iran 671 1

Pakistan 426 2

Europe

Austria 79 1

Belgium 783 5

Denmark 895 1

UK 1565 15

Finland 394 2

France 1022 10

Germany 2177 16

Ireland 157 1

Israel 854 7


Regions N Centers

Italy 489 7

Netherlands 447 8

Norway 57 1

Poland 363 4

Portugal 127 2

Spain 562 8

Sweden 781 4

Switzerland 480 3

Russia 91 1

Turkey 339 3

Greece 3 1

Czech Republic 412 3

Slovak Republic 92 1

Southeastern Asia

India 1268 9

Western Pacific

Australia 2466 15

Korea 2655 3

New Zealand 601 4

Taiwan 62 1

Hong Kong 29 1

Singapore 557 3


Table 6. Number of patients who received a first allogeneic transplant registered with the CIBMTR between 2000 and 2017 (TED)

CRF TED

Country

Malignant

disease

Non-malignant

disease

Malignant

disease

Non-malignant

disease

Argentina 100-500 <100 501-999 100-500

Australia 501-999 100-500 ≥1000 501-999

Austria <100 <100 100-500 <100

Belgium 100-500 <100 ≥1000 100-500

Brazil 501-999 100-500 ≥1000 ≥1000

Canada 501-999 100-500 ≥1000 501-999

China <100 <100 <100 <100

Colombia <100 <100 100-500 <100

Czech Republic 100-500 <100 501-999 <100

Denmark 100-500 <100 ≥1000 100-500

Egypt <100 NA 501-999 100-500

Finland <100 <100 501-999 <100

France 100-500 <100 ≥1000 100-500

Germany ≥1000 <100 ≥1000 100-500

Hong Kong <100 <100 100-500 <100

Hungary <100 NA <100 <100

India 100-500 100-500 501-999 501-999

Iran 100-500 100-500 ≥1000 501-999

Ireland 100-500 <100 100-500 <100

Israel 100-500 <100 ≥1000 100-500

Italy <100 <100 ≥1000 100-500

Japan 501-999 <100 501-999 <100

Korea 501-999 100-500 ≥1000 501-999

Mexico <100 <100 100-500 <100

Netherlands <100 <100 501-999 <100

New Zealand 100-500 <100 501-999 100-500


CRF TED

Country

Malignant

disease

Non-malignant

disease

Malignant

disease

Non-malignant

disease

Norway <100 <100 <100 <100

Pakistan <100 100-500 100-500 501-999

Peru <100 <100 <100 <100

Poland 100-500 <100 501-999 <100

Portugal <100 <100 100-500 <100

Russia <100 <100 100-500 <100

Saudi Arabia 501-999 501-999 ≥1000 ≥1000

Singapore 100-500 <100 501-999 <100

Slovak Republic <100 <100 100-500 <100

South Africa 100-500 <100 100-500 <100

Spain 100-500 <100 ≥1000 100-500

Sweden 100-500 <100 ≥1000 100-500

Switzerland <100 <100 501-999 <100

Taiwan <100 NA 100-500 <100

Turkey <100 <100 501-999 <100

UK 100-500 100-500 ≥1000 501-999

USA ≥1000 ≥1000 ≥1000 ≥1000

Uruguay <100 <100 100-500 <100

Venezuela <100 <100 100-500 <100 Countries with <100 patients in both CRF and TED dataset are not included in this report.


Table 7. Number of patients who received a first autologous transplant registered to the CIBMTR between 2000 and 2017 (TED)

CRF TED

Country Malignant

disease Non-malignant

disease Malignant


disease

Argentina 100-500 NA ≥1000 <100

Australia <100 <100 ≥1000 <100

Austria <100 NA 100-500 <100

Belgium <100 NA 501-999 <100

Brazil 100-500 <100 ≥1000 <100

Canada 501-999 <100 ≥1000 <100

Colombia NA NA 100-500 <100

Czech Republic <100 NA 501-999 <100

Finland <100 NA 100-500 NA

France <100 NA 501-999 <100

Germany <100 <100 ≥1000 <100

India <100 NA 100-500 <100

Iran <100 NA 100-500 <100

Israel <100 <100 501-999 <100

Italy <100 NA 501-999 <100

Korea <100 NA 501-999 <100

Mexico <100 NA 100-500 NA

Netherlands NA NA 100-500 <100

New Zealand <100 NA 100-500 <100

Poland <100 NA 100-500 <100

Portugal NA NA 100-500 NA

Russia <100 <100 100-500 <100

Saudi Arabia <100 NA 501-999 <100

Singapore 100-500 <100 100-500 <100

South Africa <100 NA 100-500 <100

Spain <100 <100 ≥1000 <100


CRF TED

Country Malignant


disease Malignant


disease

Sweden <100 NA 100-500 <100

Switzerland NA NA 100-500 <100

Turkey <100 NA 501-999 <100

UK <100 NA ≥1000 <100

USA ≥1000 100-500 ≥1000 100-500

Uruguay 100-500 NA 501-999 <100

Venezuela <100 NA 100-500 NA


TO: Health Services and International Studies Working Committee Members

FROM: Wael Saber, MD, MS; Scientific Director for Health Services and International Studies Working Committee

RE: Studies in Progress Summary

HS12-02 Rates of transplantation in urban vs rural patients: Are rural patients less likely to receive an allogeneic transplant (K Paulson/ M Seftel/ D Szwajcer) The main objective of this study will be to establish the rate of transplantation in rural and urban patients with AML and MDS undergoing allogeneic transplantation, and determine if there is a significant difference in utilization of transplant between rural and urban patients. The study is in the analysis phase. We expect to submit the manuscript by the end of June 2018.

HS14-01 Investigating clinical outcomes and inpatient health care resource utilization of hematopoietic cell transplantation for children with acute leukemia (S Arnold/ R Aplenc/M Pulsipher/P Satwani) This study will describe inpatient health care utilization and adjusted costs of pediatric alloHCT recipients for acute leukemia change over time. The study protocol is under analysis phase. We expect to submit the manuscript by the end of June 2018.

HS15-01 Who is lost to follow-up in the center for international blood and marrow transplant research registry? (D Buchbinder/ T John/ T Hahn/ K Ballen/ W Saber/ S Parsons) This study will estimate the cumulative incidence of becoming lost to follow-up (LTFU) among hematopoietic cell transplant (HCT) recipients reported to the Center for International Blood and marrow Transplant Research (CIBMTR) registry. This study is in the protocol development phase. The goal is finish the analysis by the end of June 2018.

HS15-02 Impact of socioeconomic status on pediatric stem cell transplant outcomes (K Bona/J Wolfe/ C Duncan/ L Lehmann) First object of this study is to determine the relationship between family socioeconomic status and rates of graft-versus-host-disease in pediatric stem cell transplant. Second object of this study is to determine the relationship between family socioeconomic status and rates of post-transplant infection in pediatric stem cell transplant. This study is in data file preparation phase. The goal is to have a data set ready to analysis by the end of February 2018 and finish the analysis by the end of June 2018.

HS16-01 Trends in Utilization and Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Racial and Ethnic Minorities (N Khera/ T Hahn/ S Ailawadhi / W Saber) This study will evaluate the trends in utilization and clinical outcomes of autologous and allogeneic HCT in patients of different race/ ethnicity utilizing data collected by the Center for International Blood and Marrow Transplant Research (CIBMTR). This study is in the protocol development phase. The goal is to have the protocol completed by then end of June 2018.


HS16-02 The Impact of Marital Status on Hematopoietic Stem Cell Transplant Recipient Outcomes: A surrogate for consistent caregiver (S M Beattie/ J Tay/ C Bredeson) This study will examine marital status (surrogate for caregiver) on HSCT survival for both autologous and allogeneic transplants, include important HSCT covariates as well as include multi-center data. This study is in the protocol development phase. The goal is to have a data set ready to analysis by the end of February 2018. HS16-03 Relationship of Race/Ethnicity and Survival after Single and Double Umbilical Cord Blood Transplantation (K Ballen) This study will compare overall and disease free survivals for White, Hispanic, Asian, and Black patients after single and double umbilical cord blood transplantation; and determine if survival for White, Hispanic, Asian, and Black patients is comparable if transplanted with units of similar cell dose and HLA match. This study is in the protocol development phase. The goal is to have the protocol completed by then end of June 2018. HS17-01 Association of community health status and center survival for allogeneic hematopoietic cell transplantation (S Hong/ N Majhail/ T Hahn/ S Lee) This study will evaluate association between social determinants of health for community where patients reside (assessed by County Health Rankings based on zip code of patient residence) and patient 1-year overall survival after allogeneic HCT. This study is in the protocol development phase. The goal is to have the protocol completed by then end of June 2018.


Proposal 1707-02

Title: Patient outcomes in the first five years after centers initiate alternative donor hematopoietic cell transplant programs for hematologic malignancy

Mary-Elizabeth Muchmore Percival, MD, MS, [email protected], University of Washington/Fred Hutchinson Cancer Research Center, William Allen Wood, MD, MPH, [email protected], University of North Carolina, Chapel Hill

Hypothesis: Because initiation of alternative donor transplant programs requires experience and expertise that are significantly different than that of matched allogeneic hematopoietic cell transplant, we hypothesize that center-level outcomes of alternative donor transplants improve as a function of center experience with alternative donor transplants (years following initiation) and center volume of alternative donor transplants, after adjusting for disease risk, comorbidity and other relevant prognostic factors.

Specific aims: • To characterize center-level trends in the use of alternative donor transplantation with umbilical

cord blood and/or haploidentical HCT over time.• To evaluate the association of center-level alternative donor transplantation experience and

volume with center-level treatment-related mortality, disease-free survival, and overall survivalfollowing alternative donor transplantation.

Scientific impact: As enthusiasm spreads for alternative donor HCT in patients with hematologic malignancies, many patients are being treated at centers with less experience. We aim to examine the outcomes of patients treated at centers in the first five years of initiation of alternative donor HCT programs, and thereby see whether further recommendations should be developed to assist centers in development of alternative donor transplant programs.

Scientific justification: The advent of alternative donor transplant options has greatly expanded donor availability, such that donors can now be identified for the vast majority of patients for whom an allogeneic hematopoietic cell transplant (HCT) is recommended.1 Alternative donor transplants comprise two main categories: umbilical cord blood (UCB) and haploidentical HCT. The benefits of an expanded donor pool and the ability to rapidly mobilize donors have led to rapid increases in the number of alternative donor HCT that are performed. The outcomes are comparable to those of matched allogeneic HCT,2,3 but there is significant variability between centers in terms of which approach is preferred. Some centers perform primarily UCB HCT for patients without a matched donor,4,5 and some primarily haploidentical HCT.6 In this state of clinical equipoise, the ongoing BMT CTN 1101 trial randomizes patients without matched donors to receive double UCB vs. haploidentical HCT (NCT01597778).

The potential complications from alternative donor HCT are considerable. UCB HCT have delayed engraftment which can lead to increased infectious complications, as well as high treatment-related mortality (TRM), particularly in the myeloablative setting; these negative aspects may be offset by a significant graft-versus-leukemia effect and a decrease in chronic graft-versus-host disease (GVHD). Haploidentical transplants have relatively low TRM and GVHD, but appear to have higher relapse rates.



Balancing these competing risks and becoming familiar with the different conditioning and GVHD prophylaxis regimens can be complicated. Some clinical volume is required at the center to lead to the best outcomes for patients undergoing allogeneic transplant, as was demonstrated many years ago in a CIBMTR study demonstrating that outcomes were substantially improved at centers performing at least 5 transplants per year.7 We hypothesize that there is a relationship between outcomes and both clinical experience (measured per center each year over the first five years of alternative donor transplants) and clinical volume (measured as number of alternative donor transplants performed annually). Patient eligibility population: Inclusion:

• Age ≥ 18 years • Year of transplant after 2000 • First allogeneic HCTs using either UCB or haploidentical donor • HCT performed at a center within the first 5 years of initiation of UCB or haploidentical program

Data requirements: No additional data collection from sites is required. Baseline variables to be collected or calculated include age, gender, diagnosis, CIBMTR disease status, DRI, HCT-CI, KPS, conditioning regimen intensity, and center volume (see Study Design below). The outcome variables will be treatment-related mortality (death within the first 100 days post-transplant), disease-free survival, and overall survival. Study design: Using the CIBMTR database, we will first describe the increase in centers initiating alternative donor HCT programs over time, including UCB, haploidentical, or both (Specific Aim 1). We will next examine outcomes over the first five years of such alternative donor HCT programs at individual centers, stratified both by year of transplant since the alternative donor program was established (year 1, year 2, year 3, etc.) and by number of transplants performed annually (Specific Aim 2). The a priori cut point will be <5 UCB or haploidentical transplants annually at an individual center, but we will also examine outcomes after dividing centers into quintiles based on number of alternative donor transplants performed annually. We will compare baseline factors such as demographics, using Fisher’s exact test and the Wilcoxon rank sum test where appropriate. Survival estimates for various groups depending on number of transplants annually will be calculated using the Kaplan-Meier method and compared using a log-rank p value. Multivariate Cox proportional hazards models will be used for time-to-event modeling. References: 1. Kindwall-Keller TL, Ballen KK. Alternative Donor Graft Sources for Adults with Hematologic

Malignancies: A Donor for All Patients in 2017! Oncologist 2017. 2. Warlick ED, Peffault de Latour R, Shanley R, et al. Allogeneic hematopoietic cell transplantation

outcomes in acute myeloid leukemia: similar outcomes regardless of donor type. Biol Blood Marrow Transplant 2015;21:357-63.


3. Raiola AM, Dominietto A, di Grazia C, et al. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant 2014;20:1573-9.

4. Milano F, Gooley T, Wood B, et al. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N Engl J Med 2016;375:944-53.

5. Brunstein CG, Gutman JA, Weisdorf DJ, et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010;116:4693-9.

6. Luznik L, O'Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol 2012;39:683-93.

7. Horowitz MM, Przepiorka D, Champlin RE, et al. Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers? Blood 1992;79:2771-4.


Table1. Characteristic of adult patients (age>=18 years old) who underwent a first allogeneic transplant using cord blood between 2000 and 2015 in US registered with the CIBMTR (TED)

2000-2004 2005-2009 2010-2015

Variable

Low volume

center

High volume

center

Low volume

center

High volume

center

Low volume

center

High volume

center Number of patients 75 302 258 878 467 1357 Number of centers 22 23 52 52 50 49 Age at transplant, years, median(range) 33

(18-65) 42

(18-78) 42

(18-83) 44

(18-80) 48

(18-70) 51

(18-81) Age at transplant, years 18-19 7 (9) 27 (9) 17 (7) 48 (5) 21 (4) 52 (4) 20-29 24 (32) 58 (19) 64 (25) 166 (19) 71 (15) 189 (14) 30-39 12 (16) 55 (18) 42 (16) 148 (17) 90 (19) 202 (15) 40-49 17 (23) 69 (23) 40 (16) 183 (21) 73 (16) 222 (16) 50-59 13 (17) 64 (21) 63 (24) 196 (22) 105 (22) 298 (22) 60-69 2 (3) 27 (9) 31 (12) 125 (14) 105 (22) 331 (24) >=70 0 2 (<1) 1 (<1) 12 (1) 2 (<1) 63 (5) Gender Male 39 (52) 178 (59) 122 (47) 452 (51) 253 (54) 730 (54) Female 36 (48) 124 (41) 136 (53) 426 (49) 214 (46) 627 (46) Karnofsky score prior to transplant <90 40 (53) 202 (67) 82 (32) 380 (43) 172 (37) 417 (31) >=90 9 (12) 27 (9) 132 (51) 419 (48) 287 (61) 916 (68) Missing 26 (35) 73 (24) 44 (17) 79 (9) 8 (2) 24 (2) Disease Acute myelogenous leukemia or ANLL 22 (29) 109 (36) 143 (55) 380 (43) 242 (52) 678 (50) Acute lymphoblastic leukemia 17 (23) 56 (19) 48 (19) 150 (17) 81 (17) 250 (18) Other leukemia 5 (7) 9 (3) 6 (2) 44 (5) 11 (2) 35 (3) Chronic myelogenous leukemia 9 (12) 32 (11) 10 (4) 38 (4) 17 (4) 45 (3) Myelodysplastic/ Myeloproliferative disorders

5 (7) 28 (9) 24 (9) 99 (11) 55 (12) 175 (13)

Other acute leukemia 2 (3) 4 (1) 6 (2) 13 (1) 7 (1) 19 (1) Non-Hodgkin lymphoma 8 (11) 44 (15) 8 (3) 99 (11) 42 (9) 107 (8) Hodgkin lymphoma 3 (4) 5 (2) 2 (<1) 12 (1) 6 (1) 9 (<1) Plasma cell disorder/Multiple Myeloma 0 1 (<1) 0 1 (<1) 1 (<1) 5 (<1) Other Malignancies 2 (3) 3 (<1) 0 1 (<1) 0 0 Severe aplastic anemia 1 (1) 5 (2) 8 (3) 23 (3) 2 (<1) 16 (1)


2000-2004 2005-2009 2010-2015

Variable

Low volume

center

High volume

center

Low volume

center

High volume

center

Low volume

center

High volume

center Inherited abnormalities erythrocyte differentiation or function

1 (1) 1 (<1) 0 8 (<1) 0 9 (<1)

SCID and other immune system disorders

0 1 (<1) 0 4 (<1) 2 (<1) 4 (<1)

Inherited abnormalities of platelets 0 0 0 0 0 1 (<1) Inherited disorders of metabolism 0 4 (1) 0 6 (<1) 0 2 (<1) Histiocytic disorders 0 0 0 0 0 2 (<1) Autoimmune Diseases 0 0 3 (1) 0 0 0 Other, specify 0 0 0 0 1 (<1) 0 Race Caucasian 52 (69) 253 (84) 189 (73) 687 (78) 336 (72) 991 (73) African-American 12 (16) 25 (8) 42 (16) 105 (12) 68 (15) 201 (15) Asian 4 (5) 3 (<1) 17 (7) 41 (5) 40 (9) 102 (8) Pacific islander 0 0 1 (<1) 4 (<1) 3 (<1) 9 (<1) Native American 0 2 (<1) 1 (<1) 2 (<1) 3 (<1) 9 (<1) Other 7 (9) 15 (5) 1 (<1) 21 (2) 0 0 Unknown 0 4 (1) 7 (3) 18 (2) 17 (4) 45 (3) Median follow-up of survivors (range), months 144

(4-192) 144

(3-197) 95

(11-122) 94

(3-147) 37

(3-88) 37

(3-81)


Table2. Characteristic of adult patients (age>=18 years old) who underwent a first allogeneic transplant using haploidentical donor between 2000 and 2015 in US registered with the CIBMTR (TED)

2000-2004 2005-2009 2010-2015

Variable

Low volume

center

High volume

center

Low volume

center

High volume

center

Low volume

center

High volume

center Number of patients 111 384 100 378 236 1008 Number of centers 41 42 37 38 51 52 Age at transplant, years, median(range) 45

(18-70) 45

(18-83) 47

(18-74) 51

(18-77) 53

(19-82) 55

(18-78) Age at transplant, years 18-19 3 (3) 19 (5) 3 (3) 12 (3) 4 (2) 30 (3) 20-29 20 (18) 71 (18) 18 (18) 46 (12) 28 (12) 142 (14) 30-39 19 (17) 63 (16) 14 (14) 34 (9) 29 (12) 97 (10) 40-49 36 (32) 88 (23) 20 (20) 83 (22) 40 (17) 122 (12) 50-59 22 (20) 81 (21) 29 (29) 110 (29) 53 (22) 234 (23) 60-69 10 (9) 55 (14) 14 (14) 80 (21) 67 (28) 309 (31) >=70 1 (<1) 7 (2) 2 (2) 13 (3) 15 (6) 74 (7) Gender Male 67 (60) 237 (62) 56 (56) 233 (62) 138 (58) 605 (60) Female 44 (40) 147 (38) 44 (44) 145 (38) 98 (42) 403 (40) Karnofsky score prior to transplant <90 55 (50) 216 (56) 48 (48) 178 (47) 102 (43) 416 (41) >=90 0 4 (1) 20 (20) 99 (26) 133 (56) 558 (55) Missing 56 (50) 164 (43) 32 (32) 101 (27) 1 (<1) 34 (3) Disease Acute myelogenous leukemia or ANLL 45 (41) 145 (38) 39 (39) 156 (41) 122 (52) 419 (42) Acute lymphoblastic leukemia 14 (13) 46 (12) 16 (16) 44 (12) 35 (15) 144 (14) Other leukemia 4 (4) 14 (4) 5 (5) 35 (9) 5 (2) 27 (3) Chronic myelogenous leukemia 18 (16) 30 (8) 3 (3) 14 (4) 12 (5) 34 (3) Myelodysplastic/Myeloproliferative disorders

7 (6) 36 (9) 13 (13) 41 (11) 23 (10) 196 (19)

Other acute leukemia 1 (<1) 3 (<1) 2 (2) 2 (<1) 4 (2) 14 (1) Non-Hodgkin lymphoma 19 (17) 70 (18) 19 (19) 55 (15) 14 (6) 92 (9) Hodgkin lymphoma 0 6 (2) 0 7 (2) 2 (<1) 15 (1) Plasma cell disorder/Multiple Myeloma 0 9 (2) 0 3 (<1) 1 (<1) 7 (<1) Other Malignancies 1 (<1) 16 (4) 0 1 (<1) 0 5 (<1) Breast Cancer 0 1 (<1) 0 0 0 0 Severe aplastic anemia 2 (2) 3 (<1) 3 (3) 12 (3) 12 (5) 25 (2)


2000-2004 2005-2009 2010-2015

Variable

Low volume

center

High volume

center

Low volume

center

High volume

center

Low volume

center

High volume

center Inherited abnormalities erythrocyte differentiation or function

0 3 (<1) 0 6 (2) 3 (1) 21 (2)

SCID and other immune system disorders

0 1 (<1) 0 1 (<1) 0 6 (<1)

Inherited abnormalities of platelets 0 0 0 1 (<1) 0 0 Inherited disorders of metabolism 0 0 0 0 0 1 (<1) Histiocytic disorders 0 0 0 0 3 (1) 2 (<1) Autoimmune Diseases 0 1 (<1) 0 0 0 0 Race Caucasian 89 (80) 304 (79) 89 (89) 285 (75) 152 (64) 684 (68) African-American 7 (6) 41 (11) 5 (5) 60 (16) 50 (21) 234 (23) Asian 6 (5) 7 (2) 4 (4) 14 (4) 14 (6) 45 (4) Pacific islander 0 0 0 0 0 4 (<1) Native American 0 0 0 1 (<1) 4 (2) 0 Other 8 (7) 31 (8) 1 (1) 17 (4) 0 0 Unknown 1 (<1) 1 (<1) 1 (1) 1 (<1) 16 (7) 41 (4) Graft type Bone Marrow 33 (30) 108 (28) 16 (16) 149 (39) 113 (48) 409 (41) Peripheral Blood 78 (70) 272 (71) 84 (84) 227 (60) 123 (52) 598 (59) Missing 0 4 (1) 0 2 (<1) 0 1 (<1) Median follow-up of survivors (range), months 147

(2-190) 143

(3-197) 102

(12-146) 95

(3-144) 24

(2-73) 24

(2-73)


Proposal 1711-26

Title: International collaborative study to compare the prognosis for acute leukemia patients transplanted with intensified myeloablative regimens.

Yasuyuki Arai, MD, PhD, [email protected], National Institutes of Health (USA) / Kyoto University (JAPAN) /Japanese Society for Hematopoietic Cell Transplantation (JSHCT) AML/ALL working group, Yoshiko Atsuta, MD, PhD, [email protected], Nagoya University (JAPAN) / JSHCT Data Center, Shingo Yano, MD, PhD, [email protected], Jikei University School of Medicine (JAPAN) / JSHCT AML working Group, Shinichi Kako, MD, PhD, [email protected], Jichi Medical University Saitama Medical Center (JAPAN) / JSHCT ALL working group

Hypothesis: Intensified myeloablative regimens, such as high-dose cytarabine or etoposide added to the conventional CY/TBI or Bu/CY, can suppress the post-transplant relapse and improve the prognosis for patients both in the US and Japan.

Specific aims: • To determine the precise type and frequency of intensified myeloablative regimens used in the

conditionings for acute leukemia.• To confirm the prognostic differences between the conventional and intensified myeloablative

regimens in each patient’s characteristic such as age, comorbidity, disease risk/status, donorsource, GVHD prophylaxis and so on.

• To compare the merit/demerit of intensified regimen between the US and Japan.

Scientific impact: Applications and dosage of intensified myeloablative regimens are quite variable in each transplant center; thus summary of this data will be the fundamental epidemiological information for all the clinicians and researchers on this topic.

Comparisons of overall survival between the conventional and intensified regimens will (or will not) provide a rational for each regimen in each setting, and this can be an indicator to determine the best conditioning regimens for acute leukemia.

Collaborative and merged analyses using the two cohorts, CIBMTR and Japanese database (JSHCT), will offer more reliable and more profound discussion over the obtained data.

Scientific justification: In allogeneic hematopoietic stem cell transplantation for acute leukemia, intensified myeloablative regimens have been studied to reduce the post-transplant relapse and to improve overall survival. These regimens can reduce the post-transplant relapse. However, they may induce higher therapy-related toxicity and therefore lead to rather inferior overall survival.

Our group focused on this topic, and did analysis using the database in Japan 2015-16. According to these studies, in cord blood transplantation (CBT) for acute myeloid leukemia, addition of high-dose cytarabine showed superior overall survival to conventional CY/TBI regimen with decreased post- transplant relapse and the same level of therapy-related mortality [1]. This benefit was confirmed in CBT





for acute lymphoblastic leukemia [2], but not in other sources like bone marrow or peripheral blood stem cell (BMT/PBSCT) [3]. Moreover, addition of etoposide to CY/TBI improved the outcome in BMT/PBSCT only in patients with high-risk acute lymphoblastic leukemia in Japan [4]. These results possessed certain limitations, such as the bias in selecting donor sources or conditioning regimens, transplant center effect, and time-frame bias (older vs newer years of transplant). Moreover, CBT outcomes in Japan are relatively better, partially as a result of genetic homogeneity in the Japanese population. These biases strongly urge us to validate the results using the large cohort of CIBMTR including other regimens (Bu/CY) and to compare the merit/demerit of these regimens between the US and the Japanese cohorts. This proposed study can suggest important indicators to establish the best conditioning regimens for patients with acute leukemia. Patient Eligibility Population: Adult patients (18 years or older at transplantation) who underwent first myeloablative allogeneic stem cell transplantation (any donor source) for acute leukemia in the year 2000 or after. Data Requirements: Recipient Baseline Data (2000; Rev 1.0)

Recipient Demographics (#5Gender, #8Date of Birth), Primary Disease for HSCT (#9primary disease, #10-13AML, AML subtype, ALL subtype), Clinical Status of Recipient Prior to the Preparative Regimen (#20ABO, #21KS, #61coexisting disease), Pre-HSCT Preparative Regimen (#184-371), and HSCT history (#372)

Acute Myelogenous Leukemia Pre-HSCT Data (2010; Rev 1.0) All recipient data

Acute Lymphocytic Leukemia Pre-HSCT Data (2011; Rev 1.0) All recipient data

HSCT Infusion (2006; Rev 1.0) HSCT type, Product type, Pre-Collection Therapy (#1), and Product Processing/Manipulation (#44-91)

Confirmation of HLA Typing (2005; Rev 2.0) Tested person (#1), and HLA Typing by DNA Technology (#5-9)

100 Days Post-HSCT Data (2100; Rev 2.0) Vital Status (#1Date, #5Subsequent HSCT), Acute GVHD (#198-227therapy, #228-346GVHD report), and Subsequent HSCT (#566)

Acute Myelogenous Leukemia Post-HSCT Data (2110; Rev 1.0) All data included

Acute Lymphoblastic Leukemia Post-HSCT Data (2111; Rev 1.0) All data included

Six Months to Two Years Post-HSCT Data (2200; Rev 2.0) Vital Status (#1Date, #2Subsequent HSCT), Acute GVHD (#169-216GVHD report), Chronic GVHD (#217-288GVHD report), and Subsequent HSCT (#507)

Yearly Follow-Up for Greater Than Two Years Post-HSCT Data (2300; Rev 2.0) Vital Status (#2Date, #3Subsequent HSCT), Acute GVHD (#11-58GVHD report), Chronic GVHD (#59-130GVHD report), and Subsequent HSCT (#216)

Selective Post-Transplant Essential Data (2455; Rev 2.0) Survival (#44-56)


Recipient Death Data (2900; Rev 1.0) #1-4 Supplemental data is not required in this study.

In addition to these data, Japanese database (JSHCT) is provided to be merged and perform parallel comparisons. Study design: Two datasets from CIBMTR and JSHCT will be merged for analysis. The type and dosage of additional chemotherapies added onto conventional conditionings (CY/TBI or Bu/CY) will be summarized and categorized into several groups. Each group will be compared with the conventional regimens in terms of prognosis and regimen-related complications. Overall survival will be calculated with the Kaplan-Meier method and compared using log-rank tests for each covariant related to pre-transplant patient characteristics. Multivariate analysis will be performed with the Cox proportional hazards model. Therapy-related mortality will be analyzed considering relapse as a competing risk. The Fine-Gray proportional hazards model will be used in multivariate analyses [5]. Each comparison will also be evaluated in the subgroup analyses (e.g., age, disease risk/type/status, comorbidity, donor sources, GVHD prophylaxis, ethnicity, nationality, etc.); thus appropriate intensified regimens will be suggested in each subgroup of patient. Non-CIBMTR data source: • A description of external data source to which the CIBMTR data will be linked

Registry data obtained by Japanese Society for Hematopoietic Cell Transplantation (JSHCT) will be linked to the CIBMTR database. The JSHCT database covers all the hematopoietic cell transplantations performed in Japan including pre-transplant patient characteristics (e.g., underlying disease, previous treatments and their outcome, patients’ performance status, etc.), transplantation procedures (e.g., conditioning regimens, donor sources, GVHD prophylaxis, etc.), and post-transplant status obtained by periodical follow-ups (e.g., various complications like infection, disease status, long-term follow-up results, etc.). Overall, the JSHCT database has a very similar structure to the CIBMTR database.

• The rationale for why the linkage is required, i.e., neither database contains all the data required to

answer the study question

Linkage is necessary to enlarge the cohort size and to perform subgroup analyses comparing various nationalities and ethnicities for the results. A larger cohort will increase the power to detect the smaller outcome differences between the different types of conditioning regimens. Various subgroup analyses will suggest the appropriate application of the results, and provide direction for the future international collaborative studies.

• A list of the data elements available in both data sources that will be used to link the CIBMTR record

with the external record

All the necessary data regarding pre- and post-transplant data shown in Data Requirements will be extracted from JSHCT database and linked to CIBMTR database.


• The methodology used to link the datasets.

The anonymized data set will be forwarded from JSHCT data center, and the included variables are modified so as to match those used in CIBMTR. Modified dataset will be simply added to the end of CIBMRT database.

References: 1. Arai Y, Takeda J, Aoki K, et al. Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy. Blood. 2015;126:415-422. 2. Arai Y, Kondo T, Shigematsu A, et al. High-dose cytarabine added to CY/TBI improves the prognosis of cord blood transplantation for acute lymphoblastic leukemia in adults: a retrospective cohort study. Bone Marrow Transplant. 2016. 3. Arai Y, Aoki K, Takeda J, et al. Clinical significance of high-dose cytarabine added to cyclophosphamide/total-body irradiation in bone marrow or peripheral blood stem cell transplantation for myeloid malignancy. J Hematol Oncol. 2015;8:102. 4. Arai Y, Kondo T, Shigematsu A, et al. Improved prognosis with additional medium-dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults. Am J Hematol. 2017 in press. 5. Fine JP, Gray RJ. A Proportional Hazards Model for the Subdistribution of a Competing Risk. J Am Stat Assoc. 1999;94:496-509.


Table 1. Characteristics of adult patients (age>18 years old) who underwent first myeloablative allogeneic transplant for AML between 2000 and 2015 in US reported to the CIBMTR (CRF)

Variable bu + cy bu + cy + arac bu + cy + vp16 tbi + cy tbi + cy + arac tbi + cy + vp16 Number of patients 1854 84 66 1747 60 116 Number of centers 121 6 7 98 13 22 Age at transplant, years Median(range) 48 (18-78) 46 (19-68) 47 (22-63) 42 (18-72) 35 (18-72) 43 (18-61) 18-19 34 (2) 2 (2) 0 58 (3) 12 (20) 7 (6) 20-29 256 (14) 12 (14) 9 (14) 330 (19) 10 (17) 18 (16) 30-39 250 (13) 16 (19) 11 (17) 364 (21) 18 (30) 24 (21) 40-49 529 (29) 21 (25) 18 (27) 541 (31) 8 (13) 35 (30) 50-59 621 (33) 29 (35) 26 (39) 408 (23) 9 (15) 30 (26) 60-69 160 (9) 4 (5) 2 (3) 45 (3) 2 (3) 2 (2) >=70 4 (<1) 0 0 1 (<1) 1 (2) 0 Gender Male 936 (50) 51 (61) 34 (52) 894 (51) 31 (52) 66 (57) Female 918 (50) 33 (39) 32 (48) 853 (49) 29 (48) 50 (43) Karnofsky score prior to transplant

<90 626 (34) 25 (30) 14 (21) 556 (32) 21 (35) 56 (48) >=90 1138 (61) 59 (70) 44 (67) 1086 (62) 38 (63) 59 (51) Missing 90 (5) 0 8 (12) 105 (6) 1 (2) 1 (<1) Donor type HLA-identical sibling 632 (34) 21 (25) 17 (26) 481 (28) 13 (22) 39 (34) Other relative 50 (3) 1 (1) 1 (2) 45 (3) 6 (10) 2 (2) Unrelated 1166 (63) 62 (74) 48 (73) 1214 (69) 41 (68) 75 (65) Missing 6 (<1) 0 0 7 (<1) 0 0 Graft type Bone Marrow 427 (23) 26 (31) 47 (71) 491 (28) 32 (53) 21 (18) Peripheral Blood 1378 (74) 58 (69) 18 (27) 1200 (69) 27 (45) 90 (78) Cord Blood 49 (3) 0 1 (2) 56 (3) 1 (2) 5 (4) Year of transplant 2000-2004 379 (20) 56 (67) 45 (68) 622 (36) 32 (53) 60 (52) 2005-2009 856 (46) 25 (30) 19 (29) 719 (41) 13 (22) 36 (31) 2010-2015 619 (33) 3 (4) 2 (3) 406 (23) 15 (25) 20 (17) Median follow-up of survivors (range), months

74 (1-192) 111 (3-165) 119 (28-193) 95 (4-196) 96 (12-171) 120 (25-192)


Table 2. Characteristics of adult patients (age>18 years old) who underwent first myeloablative allogeneic transplant for ALL between 2000 and 2015 in US reported to the CIBMTR (CRF)

Variable bu + cy bu + cy + arac bu + cy + vp16 tbi + cy tbi + cy + arac tbi + cy + vp16 Number of patients 104 16 14 1287 46 126 Number of centers 47 3 6 123 10 35 Age at transplant, years Median(range) 39 (20-65) 30 (22-52) 36 (23-61) 35 (18-64) 22 (18-62) 30 (18-63) 18-19 2 (2) 0 0 82 (6) 15 (33) 14 (11) 20-29 35 (34) 8 (50) 4 (29) 402 (31) 16 (35) 46 (37) 30-39 16 (15) 3 (19) 6 (43) 301 (23) 7 (15) 28 (22) 40-49 19 (18) 3 (19) 3 (21) 302 (23) 2 (4) 17 (13) 50-59 27 (26) 2 (13) 0 188 (15) 4 (9) 20 (16) 60-69 5 (5) 0 1 (7) 12 (<1) 2 (4) 1 (<1) Gender Male 68 (65) 10 (63) 6 (43) 761 (59) 27 (59) 82 (65) Female 36 (35) 6 (38) 8 (57) 526 (41) 19 (41) 44 (35) Karnofsky score prior to transplant

<90 42 (40) 3 (19) 4 (29) 422 (33) 13 (28) 39 (31) >=90 57 (55) 12 (75) 9 (64) 784 (61) 33 (72) 82 (65) Missing 5 (5) 1 (6) 1 (7) 81 (6) 0 5 (4) Donor type HLA-identical sibling

42 (40) 1 (6) 3 (21) 297 (23) 11 (24) 28 (22)

Other relative 5 (5) 0 0 42 (3) 2 (4) 2 (2) Unrelated 56 (54) 15 (94) 11 (79) 945 (73) 33 (72) 95 (75) Missing 1 (<1) 0 0 3 (<1) 0 1 (<1) Graft type Bone Marrow 21 (20) 9 (56) 11 (79) 384 (30) 25 (54) 38 (30) Peripheral Blood 79 (76) 7 (44) 3 (21) 867 (67) 20 (43) 83 (66) Cord Blood 4 (4) 0 0 36 (3) 1 (2) 5 (4) Year of transplant 2000-2004 41 (39) 14 (88) 11 (79) 390 (30) 25 (54) 53 (42) 2005-2009 40 (38) 2 (13) 2 (14) 513 (40) 15 (33) 49 (39) 2010-2015 23 (22) 0 1 (7) 384 (30) 6 (13) 24 (19) Median follow-up of survivors (range), months

96 (12-145) 104 (63-104) 125 (96-145) 76 (8-196) 101 (12-189) 98 (12-170)


Proposal 1711-27

Title: Fludarabine/busulfan versus fludarabine/melphalan conditioning in patients with acute lymphoblastic leukemia; An international collaborative study of cohorts from the US and Japan.

Yasuyuki Arai, MD, PhD, [email protected], National Institutes of Health (USA) / Kyoto University (JAPAN) / Japanese Society for Hematopoietic Cell Transplantation (JSHCT) ALL working group, Yoshiko Atsuta, MD, PhD, [email protected], Nagoya University (JAPAN) / JSHCT Data Center, Shinichi Kako, MD, PhD, [email protected], Jichi Medical University Saitama Medical Center (JAPAN) / JSHCT ALL working group, Koji Kawamura, MD, [email protected], Jichi Medical University Saitama Medical Center (JAPAN) / JSHCT HLA working group

Hypothesis: Among reduced intensity conditioning (RIC) regimens, the fludarabine/busulfan (Flu/ivBu) regimen will demonstrate improved prognosis as compared to the fludarabine/melphalan (Flu/Mel) regimen in adult patients undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia (ALL) in the US and Japan.

Specific aims: To compare the overall survival, relapse, and non-relapse mortality between the two widely used RIC regimens (Flu/ivBu vs. Flu/Mel) in patients with ALL treated either in the US or Japan.

Scientific impact: The RIC regimen which can suppress post-transplant relapse without increasing therapy-related mortality is expected in patients with ALL especially in those with older age or various comorbidities. To determine which of the two major RIC regimens is superior will be beneficial to improve overall outcome in these ALL patients.

Collaborative and merged analyses using the two cohorts (CIBMTR in the US and JSHCT in Japan) will lead to more reliable results and also more profound discussions of the regimens available to ALL patients.

Scientific justification: Flu/ivBu and Flu/Mel are the two widely used RIC regimens in allogeneic hematopoietic stem cell transplantation. The first large scale comparison between these two regimens was in 2007, when Shimoni A, et al. showed that Flu/Mel is related to higher non-relapse mortality and lower incidence of relapse [1]. A recent study showed the same profile and no significant difference in overall survival [2].

These studies, however, mainly dealt with patients with acute myeloid leukemia. Analysis of ALL patients is not yet to be performed. As the number of allogeneic transplantation for ALL increases, more patients with older age or various comorbidities are undergoing transplantation; thus, the selection of a safer and more effective RIC regimen is all the more important. Therefore, the evidence comparing these two major RIC regimens (Flu/ivBu vs. Flu/Mel) is well needed and very important.

Our group have performed retrospective cohort study in Japan using the database of the Japanese Society for Hematopoietic Cell Transplantation (JSHCT) on this topic, and concluded Flu/ivBu could be better than Flu/Mel in the limited cohort composed of older ALL patients [3].






This proposed study will focus on this comparison of RIC regiments for ALL using the large cohort from CIBMTR and JSHCT, and it can propose important clues to establish the best RIC regimen for patients with ALL globally. Patient Eligibility Population: Adult patients (18 years or older at transplantation) who underwent first reduced-intensity allogeneic stem cell transplantation (including Flu/ivBu or Flu/Mel with or without total body irradiation) for ALL from any donor source from the year 2000 to the present. Data Requirements: The following data is necessary from each data collection form of CIBMTR. The equivalent data will be obtained from the JSHCT, and merged with CIBMTR database. Recipient Baseline Data (2000; Rev 1.0)

Recipient Demographics (#5Gender, #8Date of Birth), Primary Disease for HSCT (#9primary disease, ALL subtype), Clinical Status of Recipient Prior to the Preparative Regimen (#20ABO, #21KS, #61coexisting disease), Pre-HSCT Preparative Regimen (#184-371), and HSCT history (#372)

Acute Lymphocytic Leukemia Pre-HSCT Data (2011; Rev 1.0) All recipient data

HSCT Infusion (2006; Rev 1.0) HSCT type, Product type, Pre-Collection Therapy (#1), and Product Processing/Manipulation (#44-91)

Confirmation of HLA Typing (2005; Rev 2.0) Tested person (#1), and HLA Typing by DNA Technology (#5-9)

100 Days Post-HSCT Data (2100; Rev 2.0) Vital Status (#1Date, #5Subsequent HSCT), Acute GVHD (#198-227therapy, #228-346GVHD report), and Subsequent HSCT (#566)

Acute Lymphoblastic Leukemia Post-HSCT Data (2111; Rev 1.0) All data included

Six Months to Two Years Post-HSCT Data (2200; Rev 2.0) Vital Status (#1Date, #2Subsequent HSCT), Acute GVHD (#169-216GVHD report), Chronic GVHD (#217-288GVHD report), and Subsequent HSCT (#507)

Yearly Follow-Up for Greater Than Two Years Post-HSCT Data (2300; Rev 2.0) Vital Status (#2Date, #3Subsequent HSCT), Acute GVHD (#11-58GVHD report), Chronic GVHD (#59-130GVHD report), and Subsequent HSCT (#216)

Selective Post-Transplant Essential Data (2455; Rev 2.0) Survival (#44-56)

Recipient Death Data (2900; Rev 1.0) #1-4

Study design: Flu/ivBu will be compared with Flu/Mel regimen (either with or without total body irradiation) in terms of prognosis (i.e., overall survival and therapy-related mortality) and the incidence of relapse, graft- versus-host disease (GVHD), and other complications. Overall survival will be calculated with the Kaplan-Meier method and compared using log-rank tests for each covariant related to pre-transplant patient characteristics. Multivariate analysis will be performed with the Cox proportional hazards model. Therapy-related mortality will be analyzed considering relapse as a competing risk. The Fine-Gray proportional hazards model will be used in multivariate analyses.


Each comparison will also be evaluated in subgroup analyses (e.g., age, disease type/status, comorbidity, donor sources, GVHD prophylaxis, ethnicity, nationality, etc.); thus, the appropriate RIC regimen will be suggested for each subgroup of patients. Non-CIBMTR data source: 1. A description of external data source to which the CIBMTR data will be linked

Registry data obtained by Japanese Society for Hematopoietic Cell Transplantation (JSHCT) will be linked to the CIBMTR database. The JSHCT database covers all the hematopoietic cell transplantations performed in Japan including pre-transplant patient characteristics (e.g., underlying disease, previous treatments and their outcome, patients’ performance status, etc.), transplantation procedures (e.g., conditioning regimens, donor sources, GVHD prophylaxis, etc.), and post-transplant status obtained by periodical follow-ups (e.g., various complications like infection, disease status, long-term follow-up results, etc.). Overall, the JSHCT database has a very similar structure to the CIBMTR database. 2. The rationale for why the linkage is required, i.e., neither database contains all the data required to

answer the study question Linkage is necessary to enlarge the cohort size and to perform subgroup analyses comparing various nationalities and ethnicities for the results. A larger cohort will increase the power to detect the smaller outcome differences between the different types of conditioning regimens. Various subgroup analyses will suggest the appropriate application of the results, and provide direction for the future international collaborative studies. 3. A list of the data elements available in both data sources that will be used to link the CIBMTR record

with the external record All the necessary data regarding pre- and post-transplant data shown in Data Requirements will be extracted from JSHCT database and linked to CIBMTR database. 4. The methodology used to link the datasets. The anonymized data set will be forwarded from JSHCT data center, and the included variables are modified so as to match those used in CIBMTR. Modified dataset will be simply added to the end of CIBMRT database. References: 1. Shimoni A, Hardan I, Shem-Tov N, et al. Comparison between two fludarabine-based reduced intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia. 2007;21:2109-16. 2. Baron F, Labopin M, Peniket A, et al. Reduced-intensity conditioning with fludarabine and busulfan

versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015;121:1048-55.


3. Kawamura K, Kako S, Mizuta S, et al. Comparison of Conditioning with Fludarabine/Busulfan and Fludarabine/Melphalan in Allogeneic Transplantation Recipients 50 Years or Older. Biol Blood Marrow Transplant. 2017 (in press)


Characteristics of adult patients (age>18 years old) who received first allogeneic transplant for ALL after reduced intensity conditioning (Flu/ivBu or Flu/Mel) in US between 2000 and 2015 reported to

the CIBMTR (CRF)

Variable Flu/ivBu TBI/Flu/ivBu Flu/Mel TBI/Flu/Mel Number of patients 87 14 191 20 Number of centers 42 9 59 6 Age at transplant, years, median(range) 58 (19-70) 50 (19-67) 53 (19-72) 52 (31-72) Age at transplant, years 18-19 2 (2) 1 (7) 2 (1) 0 20-29 11 (13) 3 (21) 24 (13) 0 30-39 5 (6) 2 (14) 21 (11) 6 (30) 40-49 12 (14) 1 (7) 39 (20) 3 (15) 50-59 24 (28) 3 (21) 50 (26) 3 (15) 60-69 32 (37) 4 (29) 53 (28) 7 (35) >=70 1 (1) 0 2 (1) 1 (5) Gender Male 45 (52) 8 (57) 106 (55) 10 (50) Female 42 (48) 6 (43) 85 (45) 10 (50) Karnofsky score prior to transplant <90 49 (56) 5 (36) 74 (39) 13 (65) >=90 38 (44) 9 (64) 112 (59) 7 (35) Missing 0 0 5 (3) 0 Race Caucasian 65 (75) 10 (71) 136 (71) 14 (70) African-American 2 (2) 0 10 (5) 4 (20) Asian 19 (22) 3 (21) 30 (16) 1 (5) Pacific islander 0 0 3 (2) 0 Native American 0 0 3 (2) 0 More than one race 0 0 1 (<1) 0 Missing 1 (1) 1 (7) 8 (4) 1 (5) Donor type HLA-identical sibling 18 (21) 3 (21) 49 (26) 4 (20) Other relative 6 (7) 3 (21) 21 (11) 8 (40) Unrelated 63 (72) 8 (57) 119 (62) 8 (40) Missing 0 0 2 (1) 0 Graft type Bone Marrow 9 (10) 0 31 (16) 3 (15) Peripheral Blood 77 (89) 13 (93) 130 (68) 9 (45)


Variable Flu/ivBu TBI/Flu/ivBu Flu/Mel TBI/Flu/Mel Cord Blood 1 (1) 1 (7) 30 (16) 8 (40) Disease status Early 57 (66) 11 (79) 106 (55) 11 (55) Intermediate 19 (22) 2 (14) 54 (28) 7 (35) Advanced 8 (9) 1 (7) 27 (14) 2 (10) Missing 3 (3) 0 4 (2) 0 Year of transplant 2000-2004 12 (14) 2 (14) 31 (16) 0 2005-2009 29 (33) 4 (29) 73 (38) 2 (10) 2010-2015 46 (53) 8 (57) 87 (46) 18 (90) Median follow-up of survivors (range), months 25 (3-101) 20 (3-48) 37 (3-169) 36 (12-50)


Proposal 1711-43

Title: Racial Differences in Long Term Survivor Outcomes After Allogeneic Hematopoietic Cell Transplantation

Brandon J. Blue, MD, [email protected], Saint Louis University, Navneet Majhail, MD, MS, [email protected], Taussig Cancer Institute

Hypothesis: The basis of this study is to evaluate the extent of racial disparities in long term outcomes of allogeneic hematopoietic cell transplantation (HCT). We hypothesize that ethnic/racial disparities exist in the long-term overall survival (OS) in allogeneic HCT survivors who have survived at least 2 years after transplantation in remission. Furthermore, we hypothesize that the difference in survival among racial groups can be explained by differences in non-relapse related mortality (NRM).

Specific aims: • The primary aim of this study is to evaluate long-term outcomes by ethnicity/race after

allogeneic HCT in recipients with hematologic malignancies who have survived for at least 2years in remission after transplantation. Probability of OS, NRM and relapse at 7 years post-transplant (5 years after cohort inclusion, since patients need to be in remission for 2 years) willbe estimated in White, Black, Hispanic, Asian/Pacific Islander, and other race category patients.

Scientific impact: During the pre-transplantation phase, patients undergo an extensive consent process, weighing the risk/benefit. We know ethnic minorities have worse overall survival after transplant, however, whether these disparities persist in long-term survivors is not known. Understanding how race impacts the long-term outcomes will assist current practice guidelines in detection and surveillance of complications post stem cell transplant.

Scientific justification It has been shown ethnic minorities had worse overall survival compared to Whites.[1] Prior studies were unable to attribute that difference in survival to treatment related mortality, disease relapse, or acute or chronic GVHD.[2] Factors such as race, socioeconomic status, and insurance carrier have been associated to influence decisions on undergoing stem cell transplantation.[3] This leads one to believe there are other factors contributing to worse outcomes in ethnic minority population. We believe there is a racial disparity in the long-term outcomes in stem cell transplantation. Using the information from this study we can focus on preventing those long-term effects in select racial groups which will hopefully improve the racial disparity.

Patient eligibility population: Includes:

• Age >18 years at transplant• Diagnosis of Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia(ALL), Chronic

Myelogenous Leukemia (CML), or Myelodysplastic Syndrome(MDS) who received first allogeneicHCT from 2000-2015

• HLA matched sibling or matched unrelated donor sources


• Myeloablative and reduced-intensity transplants • Peripheral blood, bone marrow, or umbilical cord stem cell grafts • Transplant in a US center

Data requirements: Data to be analyzed will be from data collected in the CIBMTR Report forms. No supplemental data will be required. Patient, disease and transplant variables to collect as below. Patient characteristics:

• Age at transplant • Gender • Race • Karnofsky performance status at transplant • Co-morbidity index (HCT-CI) • Household annual income based on zip code of residence

Disease characteristics: • Date of cancer diagnosis • Pre-transplant induction regimen • Number of cycles induction therapy • Disease risk index • Remission status at transplant • Cytogenetics

Transplant characteristics: • Date of transplant • Preparative regimen • Donor relationship • Donor age • Donor-recipient gender match • Donor-recipient CMV status • Donor cell source- bone marrow versus peripheral blood

Outcomes: • OS • NRM • Relapse

Study design: This is a retrospective analysis examining the impact of race on long term outcomes in post-allogeneic HCT. Baseline characteristics will be compared between racial groups. The primary variable to be evaluated is survival among various ethnic racial groups and will be analyzed in a multivariable model for survival and relapse-free survival using logistic regression models. A stepwise selection process using a P-value of 0.05 will be used to identify independent predictors of outcome. Post-transplant follow-up data will be assessed at day +100, 6 months, 1 year, 2 years, and > 2 years. Variables to be considered in the multivariate analysis include age at transplant, socioeconomic status, Karnofsky performance status at transplant, cytogenetic abnormalities, disease status at transplant, number and type of chemotherapy lines prior to transplant, preparative regimen, donor relationship, and graft source. Overall survival will


be summarized using Kaplan-Meier method. Non-relapse mortality and relapse will be calculated using cumulative incidence methods. Data source: Primary data source will be the CIBMTR Research Database. No external data sources will be utilized. References: 1. Baker KS, Davies SM, Majhail NS et al. Race and socioeconomic status influence outcomes of

unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009; 15: 1543-1554.

2. Baker KS, Loberiza FR, Jr., Yu H et al. Outcome of ethnic minorities with acute or chronic leukemia treated with hematopoietic stem-cell transplantation in the United States. J Clin Oncol 2005; 23: 7032-7042.

3. Mitchell JM, Meehan KR, Kong J, Schulman KA. Access to bone marrow transplantation for leukemia and lymphoma: the role of sociodemographic factors. J Clin Oncol 1997; 15: 2644-2651.


Characteristics of adult patients (age>18 years old) who received first allogeneic transplant for AML/ALL/CM/MDS between 2003 and 2015 in US and survived for at least 2 years in remission reported to the CIBMTR (CRF)

Variable Caucasian African-

American Asian Pacific

islander Native

American Other More than

one race Number of patients 5343 287 195 8 26 17 33 Number of centers 155 87 63 6 21 10 21 Age at transplant, years Median(range) 50 (18-81) 42 (18-71) 42 (19-73) 44 (18-70) 40 (18-69) 38 (20-55) 38 (18-67) 18-19 139 (3) 14 (5) 2 (1) 1 (13) 1 (4) 1 (6) 4 (12) 20-29 724 (14) 49 (17) 34 (17) 1 (13) 6 (23) 4 (24) 8 (24) 30-39 731 (14) 62 (22) 53 (27) 1 (13) 6 (23) 7 (41) 5 (15) 40-49 1112 (21) 76 (26) 41 (21) 2 (25) 4 (15) 3 (18) 4 (12) 50-59 1448 (27) 49 (17) 42 (22) 2 (25) 6 (23) 2 (12) 9 (27) 60-69 1058 (20) 35 (12) 18 (9) 0 3 (12) 0 3 (9) >=70 131 (2) 2 (<1) 5 (3) 1 (13) 0 0 0 Gender Male 2974 (56) 129 (45) 98 (50) 4 (50) 11 (42) 10 (59) 19 (58) Female 2369 (44) 158 (55) 97 (50) 4 (50) 15 (58) 7 (41) 14 (42) Karnofsky score prior to transplant <90 1643 (31) 84 (29) 56 (29) 0 6 (23) 4 (24) 8 (24) >=90 3476 (65) 192 (67) 134 (69) 8 19 (73) 11 (65) 25 (76) Missing 224 (4) 11 (4) 5 (3) 0 1 (4) 2 (12) 0 Primary disease code AML 2639 (49) 149 (52) 98 (50) 3 (38) 11 (42) 6 (35) 12 (36) ALL 792 (15) 53 (18) 47 (24) 2 (25) 8 (31) 4 (24) 10 (30) CML 441 (8) 28 (10) 11 (6) 0 2 (8) 6 (35) 4 (12)




islander Native


one race MDS 1471 (28) 57 (20) 39 (20) 3 (38) 5 (19) 1 (6) 7 (21) Ethnicity Hispanic or Latino 415 (8) 9 (3) 0 1 (13) 5 (19) 16 (94) 6 (18) Not Hispanic or Latino 4817 (90) 271 (94) 192 (98) 7 (88) 20 (77) 1 (6) 27 (82) NA, non-resident of USA 7 (<1) 1 (<1) 1 (<1) 0 0 0 0 Missing 104 (2) 6 (2) 2 (1) 0 1 (4) 0 0 Donor type HLA-identical sibling 1481 (28) 81 (28) 57 (29) 5 (63) 7 (27) 17 5 (15) Other related 148 (3) 35 (12) 7 (4) 0 2 (8) 0 1 (3) Well-matched unrelated 2736 (51) 49 (17) 64 (33) 1 (13) 6 (23) 0 15 (45) Partially-matched unrelated 581 (11) 49 (17) 28 (14) 0 2 (8) 0 4 (12) Mis-matched unrelated 53 (<1) 12 (4) 1 (<1) 0 2 (8) 0 0 Multi-donor 11 (<1) 0 1 (<1) 0 0 0 0 Unrelated (matching TBD) 10 (<1) 0 2 (1) 0 0 0 0 Cord blood 323 (6) 61 (21) 35 (18) 2 (25) 7 (27) 0 8 (24) Graft type Bone Marrow 896 (17) 50 (17) 36 (18) 1 (13) 4 (15) 2 (12) 5 (15) Peripheral Blood 4124 (77) 176 (61) 124 (64) 5 (63) 15 (58) 15 (88) 20 (61) Cord Blood 323 (6) 61 (21) 35 (18) 2 (25) 7 (27) 0 8 (24) Conditioning intensity Myeloablative 4020 (75) 239 (83) 155 (79) 5 (63) 21 (81) 16 (94) 26 (79) RIC 1323 (25) 48 (17) 40 (21) 3 (38) 5 (19) 1 (6) 7 (21) Year of transplant 2003-2005 1076 (20) 55 (19) 21 (11) 1 (13) 3 (12) 9 (53) 5 (15) 2006-2008 1437 (27) 54 (19) 32 (16) 2 (25) 6 (23) 8 (47) 7 (21) 2009-2011 1248 (23) 72 (25) 56 (29) 3 (38) 7 (27) 0 12 (36)




islander Native


one race 2012-2015 1582 (30) 106 (37) 86 (44) 2 (25) 10 (38) 0 9 (27) Median follow-up of survivors (range), months 73 (24-171) 64 (24-169) 59 (24-163) 78 (37-124) 65 (24-122) 121 (41-146) 70 (24-149)

Completeness of follow-up

Time

Caucasian (N = 5343), %

African-American (N = 287), %

Asian (N = 195), %

Pacific islander (N = 8), %

Native American (N = 26), %

Other (N = 17), %

More than one race (N = 33), %

1-year 100 100 100 100 100 100 100 2-year 100 100 100 100 100 100 100 3-year 98 97 96 100 99 100 97 4-year 95 94 93 98 93 99 94

Number of patients excluded before 2 years of post-HCT follow-up

Caucasian

African-American Asian

Pacific islander

Native American Other

More than one race

Total (%)

Relapse 4508 301 153 10 16 17 38 5043 (51) Treatment related mortality 3396 309 109 12 16 11 11 3864 (39) Not relapse but not achieve 2 years follow-up

666 61 47 4 6 2 4 790 (8)

Relapse status unknown 196 19 4 0 1 0 0 220 (2)


Proposal 1711-109

Title: Racial/ethnic disparities in receipt of hematopoietic cell transplantation and subsequent resource utilization in children with acute leukemia

Lena Winestone, MD, MSHP, [email protected], Children’s Hospital of Philadelphia, Richard Aplenc, MD, PhD, MSCE, [email protected], Children’s Hospital of Philadelphia, Kelly Getz, PhD, [email protected], Children’s Hospital of Philadelphia

Hypothesis: Black and Hispanic patients undergo hematopoietic cell transplantation (HCT) less frequently than White non-Hispanic patients. Minority children have greater ICU utilization, increased total length of stay, and more frequent readmissions.

Specific aims: • Among a cohort of pediatric acute leukemia patients, compare the rates of hematopoietic cell

transplant by donor source between racial/ethnic minorities compared to the White non-Hispanic populations (accounting for SES).

• Among those who received stem cell transplants, compare resource utilization by race andethnicity (accounting for donor source).

• Among those who received stem cell transplants, evaluate the role of pre-transplant resourceutilization in predicting post-transplant resource utilization (and outcomes) by race and ethnicity.

Scientific impact: Allogeneic HCT is a potentially curative treatment for children with high-risk hematologic malignancies. We plan to examine access to HCT by race and determine the role that race may play in resource utilization post-transplant. The availability of matched donors for stem cell transplant may contribute to the disparate leukemia outcomes for minorities. In the two pediatric cooperative group trials, fewer Black children had related donors identified for stem cell transplantation. In addition, overall survival and disease-free survival were lower in Black children without donors than in White children without donors. Moreover, when a matched donor is not available for stem cell transplant, there is controversy about the optimal therapeutic approach, namely whether HCT should be undertaken. As a result the decision to refer to HCT, the recommendation to move forward with HCT, and the donor selection process vary significantly across patients, providers, and institutions. While some of these questions have previously been addressed or are currently under study using CIBMTR data, none have focused explicitly on the pediatric population. Our cohort of over 15,000 pediatric acute leukemia patients (in the Pediatric Health Information System database) presents a unique opportunity to examine the frequency of HCT by race and to incorporate information about resource utilization prior to and following HCT in a detailed and granular way. A better appreciation of the role that HCT plays in racial/ethnic disparities in pediatric leukemia outcomes will add to our ability to shape leukemia care, improve access to HCT, and reduce existing disparities.

Scientific justification: Management of high risk and refractory acute leukemia is variable with allogeneic hematopoietic stem cell transplant (HSCT) as a mainstay. Majhail et al. identified 3 areas of racial disparities related to HCT: donor availability, access to HCT, and outcomes of HCT. Previous literature suggests that Black adults have less access to HCT when compared to White adults (Majhail et al. 2012). The lower availability of


matched donors for HCT likely contributes to the outcome disparities observed in Black children. In the two largest pediatric cooperative group trials, fewer Black children had related donors identified for HSCT (Aplenc et al. 2006). In addition, overall survival and disease-free survival were lower in Black children without donors than in White children without donors. A recently published CIBMTR study demonstrated that the stem cell transplant utilization rate was lower amongst both Hispanic and Black patients compared to non-Hispanic White patients with multiple myeloma (Schriber et al. 2017). In particular, a previous study merging CIBMTR with SEER demonstrated White patients were twice as likely to receive an unrelated donor transplant compared to Black patients (Joshua et al. 2010). This study, performed on data from 1997 to 2002, identified lack of information about initial presentation at diagnosis and co-morbidities as one of its limitations (which is something that we hope to address with Aim 3 and have previously published on in pediatric AML (Winestone, Getz, Miller, Li, et al. 2017; Winestone, Getz, Miller, Wilkes, et al. 2017)). Moreover, since 2002 alternative donor sources including haploidentical HCT and cord blood HCT have become increasingly common (El-Cheikh et al. 2015), which are modalities particularly well suited to children given the presence of relatively young, living parents and their smaller size. No single database exists that contains extensive information on transplantation characteristics as well as healthcare resource utilization. The Pediatric Health Information System (PHIS) database is a comparative pediatric database that includes clinical and resource utilization data for inpatient, emergency department and observation unit patient encounters for over 45 freestanding pediatric hospitals across the United States, including 19 transplant centers. Data elements in the PHIS database include demographics, dates of admission and discharge, discharge diagnosis and procedures codes, length of stay and adjusted hospital charges. The PHIS data also contain billing data corresponding to specific resources utilized including inpatient pharmaceutical agents with medication name and route of administration. Our group has extensive experience with the PHIS database and has applied these data to explore resource utilization in pediatric oncology patients in a variety of ways (Lothstein et al. 2013; Fisher et al. 2009; Fisher et al. 2013; de Blank et al. 2013; Kavcic, Fisher, Li, et al. 2013; Kavcic, Fisher, Seif, et al. 2013; Fisher et al. 2014; Walker et al. 2013). Our group has also successfully merged this dataset with other databases (Li et al. 2015; Miller et al. 2015; Miller et al. 2016; Aplenc et al. 2012), including recently with data from Center for International Blood and Marrow Transplant Research (CIBMTR), the most comprehensive database of clinical information on transplanted patients (HS14-01) (Arnold et al. 2016). The use of PHIS and CIBMTR in tandem – to identify a nationally representative cohort of leukemia patients from PHIS and the subset that received stem cell transplant from CIBMTR - can be leveraged to assess the association between race/ethnicity, receipt of transplant, and posttransplant resource utilization. To investigate the etiology of disparities in leukemia outcomes, we propose to use a previous merge of Center for International Blood and Marrow Transplant Research (CIMBTR) data with the Pediatric Health Information System (PHIS) database. This dataset presents a unique opportunity to investigate the relationships between race, ethnicity, and genetics, as it will contain information about each pediatric patient’s HLA-type, which is linked to genetic ancestry (Madbouly et al. 2017). Patient eligibility population: This cohort will include patients 0-21 years who received an allogeneic HSCT for treatment of acute leukemia (ALL or AML) from 2000 – 2014.


Data requirements: We propose to use the following Transplant Essential Data forms in the CIBMTR database:

• Pre-Transplant Essential Data and Pre-Transplant Essential Data: Disease Classification (2400 and 2402) • Infectious Disease Markers (2004), Confirmation of HLA Typing (2005), HCT Infusion (2006) • Post-Transplant Essential Data (2450) at 100 days, 6 months, 1 year, and 2 years

Data elements from Pre-Transplant Essential Data form will be used to define the exposures: • Race • Ethnicity

We will collect the following data elements to serve as covariates for potential inclusion in a multivariable regression model:

• Demographic information: Date of birth, sex, zip code (to derive SES information), performance score, comorbid conditions • Diagnostic information: Reason for HCT, date of diagnosis, primary disease, leukemia classification, cytogenetic abnormalities, molecular markers, CNS involvement, disease status at transplant, number of cycles for complete remission, date of pre-transplant/most recent relapse • Transplant-related information: Date of HCT, HSC source, product type, product manipulation, CMV sero-status of donor and recipient, HLA type of donor and recipient, total nucleated cells, total number of CD34+ cells, actual weight at initiation, actual height at initiation, conditioning regimen, GVHD prophylaxis

Data elements from Post-Transplant Essential Data forms will be used to compile secondary outcome data including:

• Date of initial ANC recovery, Date of initial ANC recovery • Percent donor cells engrafted (chimerism) • Presence or absence of acute graft versus host disease and chronic graft versus host disease • Relapse including date of relapse • Graft failure including date of relapse • Mortality including cause and date of death

Study design: This will be a retrospective analysis of pediatric leukemia patients undergoing HSCT at centers that contribute to both CIBMTR and PHIS databases. This cohort will be established in a manner similar to protocol HS14-01, using a probabilistic merge strategy based on institutional codes, date of birth, and date of transplant. Exposure: The primary exposures of interest are race and ethnicity. These two data elements from CIBMTR will be combined into the following standard categories: White Non-Hispanic, Black Non- Hispanic, Hispanic, Asian, American Indian, Pacific Islander. Because these data are also captured in PHIS, we will plan to evaluate concordance between the two data sets and perform a sensitivity analysis to confirm that, when defined by PHIS, the results of the analysis are similar.


For Aim 3, several exposures will be evaluated within the time window of 100 days prior to HCT including in hospital days, ICU days, and organ system failure. Covariates: Demographic, diagnostic and transplant-related covariates will be captured from the CIBMTR database as above. Outcomes: The primary outcome for Aim 1 will be receipt of stem cell transplant, with donor source as a predefined secondary outcome. For Aims 2 and 3, the outcome of interest will be post-transplant resource utilization during the first 100 days post transplant compiled from PHIS data. In particular, we are interested in evaluating ICU care utilization (by organ system) using a previously published approach (Maude et al. 2014), length of initial HCT admission, number of readmissions, and number of hospital days. Statistical Considerations:

1. Univariate analyses will be performed to assess the association between each covariate and race/ethnicity using χ2 tests and logistic regression as appropriate. a. Transplant-related variables will be evaluated for their association to the exposure and the

outcome. Those that are not associated with both exposure and outcome will not be included in the model.

2. We will construct multivariable regression models that incorporate our primary exposure data

and aforementioned covariates to assess receipt of HCT and post-transplant resource utilization in relation to race/ethnicity.

Based on prior experience with the CIBMTR and PHIS databases within our group, we estimate that approximately 800 patients will be included in the final cohort. Non-CIBMTR data source: Our group has previously worked with CIBMTR to develop a cohort of children undergoing HSCT for acute leukemia based on data merged from PHIS and CIBMTR (HS14-01 and GV17-01). The data were merged based on date of birth, date of transplant and location of transplant to create a single, robust dataset. There are 797 subjects with comprehensive CIBMTR data in the merged dataset (Arnold et al. 2016). Performing a similar merge which would include all patients with CIBMTR data to supplement the clinical information available through CIBMTR with granular data regarding resource use from the time of diagnosis through the entire HCT course, would allow us to answer questions about the differences between treatment of White non-Hispanic patients and minority patients. References: 1. Aplenc, R., T. A. Alonzo, R. B. Gerbing, F. O. Smith, S. Meshinchi, J. A. Ross, J. Perentesis, W. G.

Woods, B. J. Lange, and S. M. Davies. 2006. 'Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children's Oncology Group', Blood, 108: 74-80.

2. Aplenc, R., B. T. Fisher, Y. S. Huang, Y. Li, T. A. Alonzo, R. B. Gerbing, M. Hall, D. Bertoch, R. Keren, A. E. Seif, L. Sung, P. C. Adamson, and A. Gamis. 2012. 'Merging of the National Cancer Institute funded cooperative oncology group data with an administrative data source to develop a more effective platform for clinical trial analysis and comparative effectiveness research: a report from the Children's Oncology Group', Pharmacoepidemiol Drug Saf, 21 Suppl 2: 37-43.


3. Arnold, Staci D, Ruta Brazauskas, Naya He, Yimei Li, Prakash Satwani, Michael A Pulsipher, Matt Hall, Yoshiko Atsuta, Jignesh D Dalal, Theresa Hahn, Carmem Bonfim, Nandita Khera, Richard Aplenc, and Wael Saber. 2016. 'Role of Donor Source on Clinical Outcomes and Inpatient Resource Utilization for Hematopoietic Cell Transplantation in Children with Acute Leukemia', Blood, 128: 3575-75.

4. de Blank, P., T. Zaoutis, B. Fisher, A. Troxel, J. Kim, and R. Aplenc. 2013. 'Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer', J Pediatr, 163: 699-705.e1.

5. El-Cheikh, Jean, Roberto Crocchiolo, Sabine Furst, Stefania Bramanti, Barbara Sarina, Angela Granata, Andrea Vai, Claude Lemarie, Catherine Faucher, Bilal Mohty, Samia Harbi, Reda Bouabdallah, Norbert Vey, Armando Santoro, Christian Chabannon, Luca Castagna, and Didier Blaise. 2015. "Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies." In Cancer, 1809-16.

6. Fisher, B. T., R. Aplenc, R. Localio, K. H. Leckerman, and T. E. Zaoutis. 2009. 'Cefepime and mortality in pediatric acute myelogenous leukemia: a retrospective cohort study', Pediatr Infect Dis J, 28: 971-5.

7. Fisher, B. T., J. S. Gerber, K. H. Leckerman, A. E. Seif, Y. S. Huang, Y. Li, T. Harris, K. Torp, R. Douglas, A. Shah, D. Walker, and R. Aplenc. 2013. 'Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia', Leuk Lymphoma, 54: 1633-9.

8. Fisher, B. T., S. Singh, Y. S. Huang, Y. Li, J. Gregory, D. Walker, A. E. Seif, M. Kavcic, and R. Aplenc. 2014. 'Induction mortality, ATRA administration, and resource utilization in a nationally representative cohort of children with acute promyelocytic leukemia in the United States from 1999 to 2009', Pediatr Blood Cancer, 61: 68-73.

9. Joshua, Thomas V, J Douglas Rizzo, Mei-Jie Zhang, Parameswaran N Hari, Seira Kurian, Marcelo Pasquini, Navneet S Majhail, Stephanie J Lee, and Mary M Horowitz. 2010. "Access to hematopoietic stem cell transplantation: effect of race and sex." In Cancer, 3469-76.

10. Kavcic, M., B. T. Fisher, Y. Li, A. E. Seif, K. Torp, D. M. Walker, Y. S. Huang, G. E. Lee, S. K. Tasian, M. Vujkovic, R. Bagatell, and R. Aplenc. 2013. 'Induction mortality and resource utilization in children treated for acute myeloid leukemia at free-standing pediatric hospitals in the United States', Cancer, 119: 1916-23.

11. Kavcic, M., B. T. Fisher, A. E. Seif, Y. Li, Y. S. Huang, D. Walker, and R. Aplenc. 2013. 'Leveraging administrative data to monitor rituximab use in 2875 patients at 42 freestanding children's hospitals across the United States', J Pediatr, 162: 1252-8, 58.e1.

12. Li, Y., M. Hall, B. T. Fisher, A. E. Seif, Y. S. Huang, R. Bagatell, K. D. Getz, T. A. Alonzo, R. B. Gerbing, L. Sung, P. C. Adamson, A. Gamis, and R. Aplenc. 2015. 'Merging Children's Oncology Group Data with an External Administrative Database Using Indirect Patient Identifiers: A Report from the Children's Oncology Group', PLoS One, 10: e0143480.6

13. Lothstein, K., B. Fisher, Y. Li, A. Seif, T. Harris, K. Torp, M. Kavcic, Y. S. Huang, S. R. Rheingold, and R. Aplenc. 2013. 'Zoonotic infections in pediatric patients with acute leukemia', Pediatr Blood Cancer, 60: E160-2.

14. Madbouly, Abeer, Tao Wang, Michael Haagenson, Vanja Paunic, Cynthia Vierra-Green, Katharina Fleischhauer, Katharine C Hsu, Michael R Verneris, Navneet S Majhail, Stephanie J Lee, Stephen R Spellman, and Martin Maiers. 2017. "Investigating the Association of Genetic Admixture and Donor/Recipient Genetic Disparity with Transplant Outcomes." In Biol. Blood Marrow Transplant., 1029-37.

15. Majhail, N S, S Nayyar, M E Burton Santibanez, E A Murphy, and E M Denzen. 2012. "Racial disparities in hematopoietic cell transplantation in the United States." In Bone Marrow Transplant., 1385-90.


16. Maude, S. L., J. C. Fitzgerald, B. T. Fisher, Y. Li, Y. S. Huang, K. Torp, A. E. Seif, M. Kavcic, D. M. Walker, K. H. Leckerman, T. J. Kilbaugh, S. R. Rheingold, L. Sung, T. E. Zaoutis, R. A. Berg, V. M. Nadkarni, N. J. Thomas, and R. Aplenc. 2014. 'Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States', Pediatr Crit Care Med, 15: 112-20.

17. Miller, T. P., Y. Li, M. Kavcic, A. B. Troxel, Y. S. Huang, L. Sung, T. A. Alonzo, R. Gerbing, M. Hall, M. H. Daves, T. M. Horton, M. A. Pulsipher, J. A. Pollard, R. Bagatell, A. E. Seif, B. T. Fisher, S. Luger, A. S. Gamis, P. C. Adamson, and R. Aplenc. 2016. 'Accuracy of Adverse Event Ascertainment in Clinical Trials for Pediatric Acute Myeloid Leukemia', J Clin Oncol, 34: 1537-43.

18. Miller, T. P., A. B. Troxel, Y. Li, Y. S. Huang, T. A. Alonzo, R. B. Gerbing, M. Hall, K. Torp, B. T. Fisher, R. Bagatell, A. E. Seif, L. Sung, A. Gamis, D. Rubin, S. Luger, and R. Aplenc. 2015. 'Comparison of administrative/billing data to expected protocol-mandated chemotherapy exposure in children with acute myeloid leukemia: A report from the Children's Oncology Group', Pediatr Blood Cancer, 62: 1184-9.

19. Schriber, Jeffrey R, Parameswaran N Hari, Kwang-Woo Ahn, Mingwei Fei, Luciano J Costa, Mohamad A Kharfan-Dabaja, Miguel Angel-Diaz, Robert P Gale, Siddharatha Ganguly, Saulius K Girnius, Shahrukh Hashmi, Attaphol Pawarode, David H Vesole, Peter H Wiernik, Baldeep M Wirk, David I Marks, Taiga Nishihori, Richard F Olsson, Saad Z Usmani, Tomer M Mark, Yago L Nieto, and Anita D'Souza. 2017. "Hispanics have the lowest stem cell transplant utilization rate for autologous hematopoietic cell transplantation for multiple myeloma in the United States: A CIBMTR report." In Cancer, 3141-49.

20. Walker, D. M., B. T. Fisher, A. E. Seif, Y. S. Huang, K. Torp, Y. Li, and R. Aplenc. 2013. 'Dexrazoxane use in pediatric patients with acute lymphoblastic or myeloid leukemia from 1999 and 2009: analysis of a national cohort of patients in the Pediatric Health Information Systems database', Pediatr Blood Cancer, 60: 616-20.

21. Winestone, L. E., K. D. Getz, T. P. Miller, Y. Li, Y. S. Huang, A. E. Seif, B. T. Fisher, and R. Aplenc. 2017. 'Complications preceding early deaths in Black and White children with acute myeloid leukemia', Pediatr Blood Cancer.

22. Winestone, L. E., K. D. Getz, T. P. Miller, J. J. Wilkes, L. Sack, Y. Li, Y. S. Huang, A. E. Seif, R. Bagatell, B. T. Fisher, A. J. Epstein, and R. Aplenc. 2017. 'The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia', Am J Hematol, 92: 141-48.


Table 1. Characteristics of pediatric patients (age<21 years old) who received a first allogeneic transplant for AML after myeloablative conditioning between 2003 and 2015 in US reported to the

CIBMTR (CRF)



islander Native


one race Number of patients 1313 208 72 9 17 20 47 Number of centers 114 76 42 9 12 12 27 Age at transplant, years, median(range)

12 (<1-21) 10 (<1-21) 9 (<1-21) 12 (<1-17)

11 (4-18) 9 (<1-18) 10 (<1-21)

Age at transplant, years <1 41 (3) 9 (4) 2 (3) 1 (11) 0 2 (10) 1 (2) 1-9 547 (42) 94 (45) 37 (51) 3 (33) 7 (41) 9 (45) 22 (47) 10-21 725 (55) 105 (50) 33 (46) 5 (56) 10 (59) 9 (45) 24 (51) Gender Male 724 (55) 99 (48) 37 (51) 5 (56) 10 (59) 8 (40) 30 (64) Female 589 (45) 109 (52) 35 (49) 4 (44) 7 (41) 12 (60) 17 (36) Karnofsky score prior to transplant <90 233 (18) 28 (13) 13 (18) 1 (11) 3 (18) 2 (10) 9 (19) >=90 1019 (78) 176 (85) 58 (81) 7 (78) 12 (71) 17 (85) 36 (77) Missing 61 (5) 4 (2) 1 (1) 1 (11) 2 (12) 1 (5) 2 (4) Ethnicity Hispanic or Latino 280 (21) 9 (4) 3 (4) 1 (11) 3 (18) 15 (75) 12 (26) Not Hispanic or Latino 995 (76) 195 (94) 68 (94) 8 (89) 14 (82) 1 (5) 35 (74) Missing 38 (3) 4 (1) 1 (1) 0 0 4 (20) 0 Donor type HLA-identical sibling 222 (17) 17 (8) 16 (22) 3 (33) 1 (6) 6 (30) 4 (9) Other relative 48 (4) 20 (10) 8 (11) 1 (11) 1 (6) 6 (30) 3 (6) Unrelated 1037 (79) 170 (82) 48 (67) 5 (56) 15 (88) 8 (40) 40 (85) Missing 6 (<1) 1 (<1) 0 0 0 0 0 Graft type Bone Marrow 555 (42) 62 (30) 30 (42) 3 (33) 7 (41) 10 (50) 11 (23) Peripheral Blood 282 (21) 34 (16) 13 (18) 5 (56) 3 (18) 5 (25) 10 (21) Cord Blood 469 (36) 112 (54) 29 (40) 1 (11) 7 (41) 5 (25) 26 (55) Missing 7 (<1) 0 0 0 0 0 0 Zip code availability No 191 (15) 32 (15) 12 (17) 2 (22) 3 (18) 17 (85) 3 (6) Yes 1122 (85) 176 (85) 60 (83) 7 (78) 14 (82) 3 (15) 44 (94) Year of transplant 2003-2005 336 (26) 54 (26) 13 (18) 3 (33) 4 (24) 12 (60) 10 (21)




islander Native


one race 2006-2008 364 (28) 47 (23) 13 (18) 2 (22) 3 (18) 8 (40) 14 (30) 2009-2011 292 (22) 38 (18) 21 (29) 1 (11) 3 (18) 0 13 (28) 2012-2015 321 (24) 69 (33) 25 (35) 3 (33) 7 (41) 0 10 (21) Median follow-up of survivors (range), months

72 (3-173)

49 (3-145)

59 (12-142)

167 (25-167)

76 (13-122)

119 (57-168)

93 (12-145)


Table 2. Characteristics of pediatric patients (age<21 years old) who received a first allogeneic transplant for ALL after myeloablative conditioning between 2003 and 2014 in US reported to the

CIBMTR (CRF)

Variable Caucasian African-American Asian Pacific

islander Native


one race Number of patients 1405 182 56 4 12 35 41 Number of centers 116 66 38 4 10 12 25 Age at transplant, years, median(range)

10 (<1-21) 10 (<1-21) 10 (1-21) 13 (5-18) 12 (<1-19) 10 (<1-20)

9 (2-19)

Age at transplant, years <1 35 (2) 3 (2) 0 0 2 (17) 1 (3) 0 1-9 642 (46) 84 (46) 29 (52) 2 (50) 4 (33) 16 (46) 25 (61) 10-21 728 (52) 95 (52) 27 (48) 2 (50) 6 (50) 18 (51) 16 (39) Gender Male 856 (61) 131 (72) 35 (63) 3 (75) 7 (58) 21 (60) 27 (66) Female 549 (39) 51 (28) 21 (38) 1 (25) 5 (42) 14 (40) 14 (34) Karnofsky score prior to transplant

<90 232 (17) 21 (12) 3 (5) 3 (75) 3 (25) 4 (11) 8 (20) >=90 1089 (78) 155 (85) 49 (88) 1 (25) 7 (58) 31 (89) 33 (80) Missing 84 (6) 6 (3) 4 (7) 0 2 (17) 0 0 Ethnicity Hispanic or Latino 429 (31) 18 (10) 1 (2) 0 3 (25) 30 (86) 9 (22) Not Hispanic or Latino 943 (67) 158 (87) 53 (95) 4 9 (75) 2 (6) 32 (78) Missing 33 (2) 6 (3) 2 (2) 0 0 3 (9) 0 Donor type HLA-identical sibling 177 (13) 13 (7) 4 (7) 1 (25) 0 21 (60) 1 (2) Other relative 67 (5) 8 (4) 9 (16) 0 1 (8) 4 (11) 1 (2) Unrelated 1147 (82) 160 (88) 42 (75) 3 (75) 11 (92) 9 (26) 38 (93) Missing 14 (<1) 1 (<1) 1 (2) 0 0 1 (3) 1 (2) Graft type Bone Marrow 547 (39) 50 (27) 21 (38) 2 (50) 2 (17) 20 (57) 14 (34) Peripheral Blood 305 (22) 37 (20) 7 (13) 0 1 (8) 6 (17) 4 (10) Cord Blood 550 (39) 95 (52) 28 (50) 2 (50) 9 (75) 9 (26) 23 (56) Missing 3 (<1) 0 0 0 0 0 0 Zip code availability No 216 (15) 22 (12) 15 (27) 1 (25) 0 34 (97) 2 (5) Yes 1189 (85) 160 (88) 41 (73) 3 (75) 12 1 (3) 39 (95) Year of transplant


Variable Caucasian African-American Asian Pacific

islander Native


one race 2003-2005 414 (29) 39 (21) 12 (21) 1 (25) 4 (33) 28 (80) 9 (22) 2006-2008 474 (34) 60 (33) 18 (32) 1 (25) 2 (17) 7 (20) 11 (27) 2009-2011 226 (16) 29 (16) 10 (18) 0 1 (8) 0 10 (24) 2012-2015 291 (21) 54 (30) 16 (29) 2 (50) 5 (42) 0 11 (27) Median follow-up of survivors (range), months

85 (6-170)

72 (5-154)

85 (12-144)

99 (74-124)

36 (13-97)

113 (5-165)

62 (12-138)


Title: Do patient outcomes following hematopoietic cell transplantation vary in the time period before and immediately after introduction of an electronic health record?

Mary-Elizabeth Muchmore Percival, MD, MS, [email protected], University of Washington/Fred Hutchinson Cancer Research Center, William Allen Wood, MD, MPH, [email protected], University of North Carolina, Chapel Hill

Hypothesis: We hypothesize that introduction of an electronic health record (EHR) will negatively impact outcomes after hematopoietic cell transplantation (HCT) in the immediate twelve-month period following EHR implementation.

Specific aims: • To compare unadjusted survival outcomes (overall survival, relapse-free survival, and treatment-

related mortality) in HCT recipients in the 12-month periods before and after EHRimplementation (so-called “go live” dates)

• To compare adjusted survival outcomes in the same population using a multivariable model tocontrol for relevant factors

Scientific impact: The introduction of electronic health records (EHR) can be disruptive to clinicians managing patients and may lead to deleterious outcomes in patients with complex medical procedures such as allogeneic HCT. We propose to examine survival outcomes in the periods immediately before and after EHR implementation at transplant centers.

Scientific justification: The past decade has demonstrated a massive increase in the number of medical practices utilizing electronic health records (EHR). A linkage between adoption of EHR and Medicaid/Medicare reimbursement was established by the American Recovery and Reinvestment Act; this federal mandate led to the widespread use of EHR.1 EHR can lead to improved documentation, potential standardization of management, and increased availability of prior records to treating physicians and patients. The rapid increase in EHR systems has not been clearly associated with improved outcomes.2 Though the benefits of EHR have been touted extensively, less attention has been paid to the potential deleterious effects of the sometimes rocky process of switching to an EHR.

Studies of effect of EHR introduction are limited, and often have conflicting results. One large study examined all Medicare hospital admissions in 17 hospitals in the periods before and after EHR adoption, finding no difference in short term inpatient mortality, adverse safety events, or 30-day readmission rate.3 However, the study design using difference-in-differences and choice of outcomes were roundly criticized in the accompanying editorial;4 additionally, computerized physician order entry (CPOE) led to “unexpected” increased mortality in the pediatric setting5 and has facilitated medication errors.6 The term “e-iatrogenesis” was coined to describe the errors that can be observed and even worsened using healthcare technology such as CPOE or EHR.7

We hypothesize that there is a potentially negative relationship between introduction of an EHR, or change to a new EHR, and outcomes following HCT (both autologous and allogeneic). Since such


differences may be most obvious in a rapid roll-out rather than a gradual transition, we propose to examine patient outcomes before and after an EHR “go live” date. Patient eligibility population: Inclusion:

• Age ≥ 18 years • Year of transplant after 2000 • Allogeneic HCT performed for any disease • HCT performed at a center within the first 12 months before or after introduction of EHR or

switch to new EHR Data requirements: Additional data collection from sites will be required. A questionnaire will be sent to all US sites to determine the “go live” date for introduction of EHR or switch to new EHR in either the inpatient and outpatient setting. Once this data is obtained, the study population will be determined based on dates. Baseline variables to be collected or calculated include age, gender, diagnosis, CIBMTR disease status, HCT-CI, KPS, conditioning regimen intensity, and center volume (see Study Design below). The outcome variables will be treatment-related mortality (death within the first 100 days post-transplant), disease-free survival, and overall survival. For patients undergoing allogeneic transplant, we will also examine the rate of acute graft-versus-host-disease. Study design: Using data from the questionnaire to sites about timing of EHR implementation combined with the CIBMTR database, we will evaluate unadjusted survival outcomes in patients who have undergone allogeneic HCT in the 12-month periods before and after EHR implementation. Then a multivariable analysis will be performed to evaluate survival outcomes, adjusted for baseline variables that may affect outcomes post-transplant including demographics; whether the EHR change was in the clinic, hospital, or both; and type of transplant performed (autologous vs. allogeneic). We will compare baseline factors such as demographics, using Fisher’s exact test and the Wilcoxon rank sum test where appropriate. Survival estimates will be calculated using the Kaplan-Meier method and compared using a log-rank p value. Multivariate Cox proportional hazards models will be used for time-to-event modeling. References: 1. Medicare and Medicaid EHR Incentive Program. (Accessed October 30, 2017, at

https://ehrincentives.cms.gov/hitech/loginCredentials.action.) 2. Yanamadala S, Morrison D, Curtin C, McDonald K, Hernandez-Boussard T. Electronic Health Records

and Quality of Care: An Observational Study Modeling Impact on Mortality, Readmissions, and Complications. Medicine 2016;95:e3332.

3. Barnett ML, Mehrotra A, Jena AB. Adverse inpatient outcomes during the transition to a new electronic health record system: observational study. Bmj 2016;354:i3835.

4. Wears RL. When hospitals switch to electronic records. Bmj 2016;354:i3941. 5. Han YY, Carcillo JA, Venkataraman ST, et al. Unexpected increased mortality after implementation of

a commercially sold computerized physician order entry system. Pediatrics 2005;116:1506-12. 6. Koppel R, Metlay JP, Cohen A, et al. Role of computerized physician order entry systems in

facilitating medication errors. Jama 2005;293:1197-203.


7. Weiner JP, Kfuri T, Chan K, Fowles JB. "e-Iatrogenesis": the most critical unintended consequence of CPOE and other HIT. Journal of the American Medical Informatics Association : JAMIA 2007;14:387-8; discussion 9.


Proposal: 1711-130

Title: Race, ethnicity and outcomes of allogeneic stem cell transplantation for acute lymphoblastic leukemia in Hispanic patients.

Anne S. Renteria, M.D., [email protected], Icahn School of Medicine at Mount Sinai, Luis Isola, M.D., [email protected], Icahn School of Medicine at Mount Sinai, Nina A. Bickell, M.D., M.P.H., [email protected], Icahn School of Medicine at Mount Sinai

Hypothesis: Hispanics treated with chemotherapy and/or allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) experience lower survival rates than Non-Hispanics (1). The causes of this disparity have not been adequately studied. We hypothesize that this disparity is due to differences in disease-related characteristics and barriers to access to treatment leading to worse outcomes.

Specific aims: Our main goal is to investigate if the differences in outcomes experienced by Hispanics vs Non-Hispanics with ALL can be explained by disease-related characteristics, less access to HCT, or both.

• We will compare cytogenetics and ALL-related risk factors (age, WBC at diagnosis, CNSinvolvement, response to chemotherapy) between Hispanic and Non-Hispanic patients.

• We will study access to HCT by comparing the treatment received by Hispanics vs Non-Hispanicswith similar demographics and disease characteristics (similar cytogenetics, disease risk factorsand status at transplant). Incidence of disease will be obtained from the SEER database. Accessto HCT through SPARCS-VR dataset for New York State (distance to center - Zip code, insurance).

• For Hispanics and Non-Hispanics with ALL receiving the same treatments we will study if theoutcomes are significantly different between these two groups (overall survival, relapse,leukemia-free survival, CNS relapse, non-relapse mortality).

Scientific impact: Race/ethnicity remains an important barrier in cancer care in the United States (2). Studies on disparities in HCT access and outcomes are limited, and much of the literature is in consensus that disparities based on race/ethnicity and socioeconomic status prevail (3-7). This study aims to investigate if lower rates of HCT and survival for Hispanics are related to health system factors and racial/ethnic characteristics. The identification of specific Hispanic patient characteristics will support targeted interventions for the design of future clinical trials aiming at improving outcomes.

Scientific justification: ALL outcomes by Race/Ethnicity. ALL is an aggressive and cytogenetically heterogeneous disease. There will be 6,000 estimated new cases of ALL in the US in 2017 (8), and in 2013 there were 78,000 people living with ALL in the US. ALL is most frequently diagnosed among people aged less than 20 years old, however a third of the cases occur in patients above 35, and with a higher incidence in the Hispanic population (9-11). For the adult patients, chemotherapy alone is often insufficient to ensure long term remissions, and HCT currently represents a important option for a cure (12, 13).


Minority patients with ALL experience lower survival rates than non-minority patients (14) when treated with either chemotherapy alone or with HCT (1, 15, 16). Studies on the outcomes of childhood ALL show that for children with high-risk leukemia, Hispanics have significantly worse outcomes than Non-Hispanics (4, 17). When disease prognostic variables are adjusted the suggestion is that, at least for children with ALL treated with standard chemotherapy protocols, Hispanic ethnicity is an independent predictor of outcomes (18, 19). This question has not been adequately studied in adults with ALL, and the reasons for disparities are not clear. Studies show that ALL is the most common indication for HCT in Hispanics, but also that they are likely to receive HCT more than one year after diagnosis when compared with Non-Hispanics, therefore with increase in risk of relapse (5). HCT is associated with a significant rate of treatment related morbidity and mortality (TRM), including conditioning toxicities, graft-versus-host disease, and infectious complications. Several factors are known to influence TRM (12) and relapse risk. Differences in transplant survival cannot be explained by any single transplantation-related complication. The use of HCT in minority groups has been increasing (20), and the Hispanic population is one of the fastest growing segment of the US population (21)[22] and a better understanding of the underlying biologic differences in HCT combined with the clinical approaches that impact outcomes is critical step to redressing the poorer outcomes Hispanic experience. In addition to biologic and clinical causes for disparate outcomes, Hispanics are more likely to be uninsured and impoverished compared to Non-Hispanics and are at greater risk of reduced access to high quality health care (22). Differences in outcomes of ALL patients of different races and ethnicities are also attributed to differences in disease biology. For example, Ph-like ALL is most often diagnosed in Hispanic patients (23) and represents an ALL subtype with poor prognosis. The systematic analysis of the incidence of distinct cytogenetic abnormalities and consequently risk groups have not been properly undertaken for Hispanic ALL patients in the US. . The Surveillance, Epidemiology, and End Results (SEER) database will enable us estimate the annual incidence of ALL in the US by age, sex, race, ethnicity for all patients. The Statewide Planning and Research Cooperative System (SPARCS) provides data for New York State regarding patient characteristics, diagnoses, treatments, and services provided, enabling us to evaluate patient’s access to transplant and their survival. The Health Resources and Services Administration (HRSA) from the U.S. Department of Health and Human Services (24), through the CIBMTR, provides data including outcomes for patients who received a transplant in New York State, and by center. The CIBMTR database provides transplant-related information for the U.S. and will allow us to compare ALL outcomes for Hispanics in New York State to Non-Hispanic in New York State and the whole country. Patient eligibility population:

• All patients who have undergone a HCT for a diagnosis of ALL between 2010 and 2015 • Age at diagnosis: < 21 yo vs ≥ 21 yo • Ethnicity and Race: Hispanic (Black-Hispanic, White-Hispanic) and Non-Hispanic (Black, White,

American Indian or Alaska Native, Asian, Pacific Islander • Treatments and outcomes data collected on the existing data collection forms. No additional

information is expected to be required from the transplant centers.


Data requirements: • Data collection forms needed: 2400, 2402, 2450, 2000, 2100, 2011, 2111 • Data from the National Cancer Institute’s SEER registry to calculate the annual incidence of ALL

in the Hispanic population in the US by age, sex, race, ethnicity for all patients. • The Statewide Planning and Research Cooperative System (SPARCS) provides data for New York

State regarding patient characteristics, diagnoses, treatments, and services provided, enabling us to evaluate patient’s access to transplant and their survival.

• The Health Resources and Services Administration (HRSA) from the U.S. Department of Health and Human Services [https://bloodcell.transplant.hrsa.gov/RESEARCH/Transplant_Data/US_Tx_Data/Data_by_Center/center.aspx], through the CIBMTR, provides data including outcomes for patients who received a transplant in New York State, and by center.

• The CIBMTR database provides transplant-related information for the U.S. and will allow us to compare ALL outcomes for Hispanics in New York State to Non-Hispanic in New York State and the whole country.

Main effect: • Patient race/ethnicity and biologic - cytogenetics Patient related: • Age: continuous, categorical by decade • Gender: female vs. male • Race: Non-Hispanic Whites (NHW), non-Hispanic African-Americans (AA) or Black, non- • Hispanic Asians/Pacific Islanders (Asians), Hispanic Whites (Hispanics) and Native • Americans (NA) [identified using the North American Association of Central Cancer • Registries (NAACCR) Hispanic/Latino Algorithm (NAACCR Race and Ethnicity Work • Group, 2011)] • Karnofsky performance score at transplant: ≥ 80 vs. < 80 • Co-morbid medical conditions: 0-1 vs. ≥ 2 conditions (Sorror HCT co-morbidity index) • Geographic regions and ZIP codes within geographic regions Disease related: • Disease type: Acute Lymphoblastic Leukemia only • Disease status at the time of transplant • Time since ALL diagnosis: ≤1 year vs. >1 year • Lines of induction therapy prior to conditioning for HCT: 1 vs. >1 • Use of tyrosine kinase inhibitors from the diagnosis of ALL • Cytogenetics: Individual abnormalities collected and then categorized separately into: • high risk, intermediate risk, standard risk (as per Appendix C) • Molecular markers associated with ALL: BCR-ABL, TEL-AML1, “other abnormality” • (question 100) • Disease subtype: T cell ALL vs. B cell ALL Transplant related: • Conditioning regimen: MAC vs RIC • Stem cell source: related, unrelated


• GVHD prophylaxis • GVHD incidence, acute and chronic, GVHD-free/relapse-free survival (GRFS) • Incidence of different cytogenetic abnormalities, disease risk categories/subtypes in • Hispanic ALL patients

o Overall and disease free survival after HCT for Hispanic ALL in different cytogenetic subgroups over time (2010 – 2015)

Study design: The current study will use the data from CIBMTR to determine the incidence of various cytogenetic abnormalities see in ALL Hispanic patients and starts at the time of first HCT with a primary endpoint of death from any cause. We will assess the absolute numbers as well as proportion of all individual cytogenetic abnormalities as well as risk categories of ALL Hispanic patients undergoing HCT. Patient-, disease-, and transplant-related factors will be compared between the two cohorts (Non-Hispanic vs Hispanic), using chi square for categorical and t-tests for continuous variables. Probabilities of survival and leukemia-free survival will be calculated using the Kaplan-Meier estimator. Change in HCT utilization rate by racial-ethnic group from 2010 to 2015 will be assessed, observed rates compared. Multivariate analysis of post-transplant outcomes by race/ ethnicity, age, interval from diagnosis to transplant, pre-HCT adverse disease status, socioeconomic status, type of medical insurance, performance status, DM, obesity, co-morbidities, place of residence by ZIP code The secondary endpoints include time to progression, relapse/progression-free survival, treatment related mortality, and incidence of acute and chronic GVHD. Data source:

• National Cancer Institute’s SEER • New York State linked Statewide Planning and Research Cooperative System (SPARCS) hospital

discharge data with Vital Records • The Health Resources and Services Administration (HRSA) from the U.S. Department of Health

and Human Services, through the CIBMTR, provides data including outcomes for patients who received a transplant in New York State, and by center.

• The CIBMTR Research Database References: 1. Wang L, Bhatia S, Gomez SL, Yasui Y. Differential inequality trends over time in survival among U.S.

children with acute lymphoblastic leukemia by race/ethnicity, age at diagnosis, and sex. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015;24(11):1781-8.

2. Hendren S, Chin N, Fisher S, Winters P, Griggs J, Mohile S, et al. Patients' barriers to receipt of cancer care, and factors associated with needing more assistance from a patient navigator. Journal of the National Medical Association. 2011;103(8):701-10.

3. Mitchell JM, Meehan KR, Kong J, Schulman KA. Access to bone marrow transplantation for leukemia and lymphoma: the role of sociodemographic factors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1997;15(7):2644-51.

4. Serna DS, Lee SJ, Zhang MJ, Baker k S, Eapen M, Horowitz MM, et al. Trends in survival rates after allogeneic hematopoietic stem-cell transplantation for acute and chronic leukemia by ethnicity in


the United States and Canada. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003;21(20):3754-60.

5. Baker KS, Loberiza FR, Jr., Yu H, Cairo MS, Bolwell BJ, Bujan-Boza WA, et al. Outcome of ethnic minorities with acute or chronic leukemia treated with hematopoietic stem-cell transplantation in the United States. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005;23(28):7032-42.

6. Mielcarek M, Gooley T, Martin PJ, Chauncey TR, Young BA, Storb R, et al. Effects of race on survival after stem cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2005;11(3):231-9.

7. Baker KS, Davies SM, Majhail NS, Hassebroek A, Klein JP, Ballen KK, et al. Race and socioeconomic status influence outcomes of unrelated donor hematopoietic cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2009;15(12):1543-54.

8. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, Available online

9. Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. The New England journal of medicine. 2014;371(11):1005-15.

10. SEER: cancer survival among US whites and minorities. NCI: Cancer Health disparities. http://www.nci.nih.gov/hewscenter/healthdisparities

11. Pullarkat ST, Danley K, Bernstein L, Brynes RK, Cozen W. High lifetime incidence of adult acute lymphoblastic leukemia among Hispanics in California. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009;18(2):611-5.

12. Ram R, Gafter-Gvili A, Vidal L, Paul M, Ben-Bassat I, Shpilberg O, et al. Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis. Cancer-Am Cancer Soc. 2010;116(14):3447-57.

13. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008;111(4):1827-33.

14. Jabo B, Morgan JW, Martinez ME, Ghamsary M, Wieduwilt MJ. Sociodemographic disparities in chemotherapy and hematopoietic cell transplantation utilization among adult acute lymphoblastic and acute myeloid leukemia patients. 2017;12(4):e0174760.

15. Majhail NS, Nayyar S, Santibanez ME, Murphy EA, Denzen EM. Racial disparities in hematopoietic cell transplantation in the United States. Bone marrow transplantation. 2012;47(11):1385-90.

16. Majhail NS, Omondi NA, Denzen E, Murphy EA, Rizzo JD. Access to hematopoietic cell transplantation in the United States. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2010;16(8):1070-5.

17. Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119(1):296-307.

18. Bhatia S, Sather HN, Heerema NA, Trigg ME, Gaynon PS, Robison LL. Racial and ethnic differences in survival of children with acute lymphoblastic leukemia. Blood. 2002;100(6):1957-64.

19. Pollock BH, DeBaun MR, Camitta BM, Shuster JJ, Ravindranath Y, Pullen DJ, et al. Racial differences in the survival of childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(4):813-23.


20. Pulte D, Redaniel MT, Jansen L, Brenner H, Jeffreys M. Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups. Haematologica. 2013;98(2):222-9.

21. U.S. Census Bureau (2014). 2014 National Population Projections Datasets. https://www.census.gov/data/datasets/2014/demo/popproj/2014-popproj.html.

22. National Research Council Panel on Hispanics in the United S. The National Academies Collection: Reports funded by National Institutes of Health. In: Tienda M, Mitchell F, editors. Hispanics and the Future of America. Washington (DC): National Academies Press (US)National Academy of Sciences.; 2006.

23. Jain N, Roberts KG, Jabbour E, Patel K, Eterovic AK, Chen K, et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood. 2017;129(5):572-81.

24. Health Resources and Services Administration (HRSA) from the U.S. Department of Health and Human Services https://bloodcell.transplant.hrsa.gov/RESEARCH/Transplant_Data/US_Tx_Data/Data_by_Center/center.aspx.


Characteristics of adult patients (age>18 years old) who underwent a first allogeneic transplant for ALL between 2003 and 2015 in US reported to the CIBMTR (CRF)

Variable Hispanic or Latino Not Hispanic or Latino Number of patients 532 2279 Number of centers 97 147 Age at transplant, years, median(range) 33 (18-69) 40 (18-75) Age at transplant, years 18-19 46 (9) 116 (5) 20-29 194 (36) 570 (25) 30-39 125 (23) 454 (20) 40-49 97 (18) 498 (22) 50-59 47 (9) 455 (20) 60-69 23 (4) 179 (8) >=70 0 7 (<1) Gender Male 320 (60) 1334 (59) Female 212 (40) 945 (41) Karnofsky score prior to transplant <90 161 (30) 825 (36) >=90 361 (68) 1347 (59) Missing 10 (2) 107 (5) Race Caucasian 423 (80) 1893 (83) African-American 7 (1) 187 (8) Asian 5 (<1) 122 (5) Pacific islander 4 (<1) 8 (<1) Native American 4 (<1) 15 (<1) Other 16 (3) 1 (<1) More than one race 5 (<1) 20 (<1) Missing 68 (13) 33 (1) Donor type HLA-identical sibling 166 (31) 506 (22) Other relative 41 (8) 148 (6) Unrelated 319 (60) 1610 (71) Missing 6 (1) 15 (<1) Graft type Bone Marrow 63 (12) 443 (19) Peripheral Blood 338 (64) 1524 (67)


Variable Hispanic or Latino Not Hispanic or Latino Cord Blood 131 (25) 312 (14) Year of transplant 2003-2005 70 (13) 552 (24) 2006-2008 155 (29) 690 (30) 2009-2011 119 (22) 365 (16) 2012-2015 188 (35) 672 (29) Median follow-up of survivors (range), months 61 (12-168) 72 (2-170)