Roger Williams Medical Center a CharterCare Health Partner

Presenter: Mark Curtis RPh Clinical Informatics Pharmacist

Discuss the current ASBMT Conditioning Discuss the current ASBMT Conditioning Regimen RecommendationsRegimen Recommendations

Recognize the importance of chemo dosing Recognize the importance of chemo dosing on outcomeson outcomes

Demonstrate how a dosing calculator can Demonstrate how a dosing calculator can support doctors, pharmacists and nursing support doctors, pharmacists and nursing in safe patient therapyin safe patient therapy

Review the findings from a retrospective Review the findings from a retrospective review of patients from 2010 through 2014.review of patients from 2010 through 2014.

Recognize the current ASBMT Recognize the current ASBMT Conditioning Regimen Conditioning Regimen RecommendationsRecommendations

Recognize the importance of Recognize the importance of appropriate chemotherapy dosing appropriate chemotherapy dosing

Understand how accurate calculations Understand how accurate calculations are needed before the preparation of are needed before the preparation of chemotherapychemotherapy

Roger Williams Medical Center a CharterCare Health Partner

Presenter: Mark Curtis RPh Clinical Informatics PharmacistHas no financial disclosures to report

Drugs Recommended DosingBusulfan use AIBW25 for all mg/kg dosing

Carmustine use BSA until TBW>120% then use AdjBSA25

Cyclophosphamide use TBW until TBW>120% of IBW then use AIBW25

Cytarabine use BSA (based on TBW)

Etoposide mg/kg use AIBW25 for all mg/kg dosing

Etoposide BSA use BSA (based on TBW)

Fludarabine use BSA (based on TBW)

Melphalan use BSA (based on TBW)

rATG use TBW for mg/kg dosing

Reference: J.Bubalo et al. Biol Blood Marrow Transplant 20 (2014) 600-616

REGIMEN Chemo DrugsDay -6

Day-5

Day-4

Day-3

Day-2

Day-1

DAY 0

BEAM Carmustine 300 mg/m2 X Etoposide 100 mg/m2 daily X X X X

Cytarabine 100 mg/m2 Q12H X X X X

Melphalan 140 mg/m2 X

Doctors, Nurses, Pharmacists all helped Doctors, Nurses, Pharmacists all helped test the calculatortest the calculator

Regimen selection, patient metrics, and Regimen selection, patient metrics, and dose calculations were all tested for dose calculations were all tested for accuracyaccuracy

Over 80 different patient examples were Over 80 different patient examples were used for testingused for testing

Any discrepancy between the calculator Any discrepancy between the calculator and the manual calculation were reviewed and the manual calculation were reviewed and reconciledand reconciled

109 patients transplanted at RWMC 109 patients transplanted at RWMC between 2010 and 2014between 2010 and 2014

Transplant types included Auto, Allo Transplant types included Auto, Allo (MRD/MUD) and Cord Blood(MRD/MUD) and Cord Blood

Reviewed dosing variances between the Reviewed dosing variances between the current ASBMT recommendations and current ASBMT recommendations and the administered dosethe administered dose

Two groups: those with out a variance Two groups: those with out a variance and those who had a varianceand those who had a variance

Outcomes were reviewed:Outcomes were reviewed:

Days to Engraftment of ANC and PlateletsDays to Engraftment of ANC and Platelets

Relapse ratesRelapse rates

Survivor ratesSurvivor rates

It is very difficult to confirm cause and It is very difficult to confirm cause and effect….effect….

Dosing Variances (Table 1)

Conditioning

Transplant Type N

Calc Dose Same

Calc Dose Variance

BEAM AUTO 23 8 15Bu/Cy ALLO MUD 8 2 6Bu/Cy ALLO MRD 2 0 2Flu/Bu ALLO MUD 18 3 15Flu/Bu ALLO MRD 7 0 7

Flu/Cy /TBI Cord Blood 6 4 2Melphalan 140 AUTO 26 10 16Melphalan 200 AUTO 19 8 11

Totals109 35 74

Dosing Variances by Drug (Table 2)Conditioni

ng Drugs NHigh Low

Wrong AdjBSA

Wrong AIBW

BEAM Carmustine 23 15 0 15 0BEAM Etoposide 23 0 14 14 0BEAM Cytarabine 23 0 14 14 0BEAM Melphalan 23 0 14 14 0Bu/Cy Busulfan 10 6 2 0 8Bu/Cy Cyclophosphamide 10 5 0 0 5Flu/Bu Fludarabine 25 0 11 11 0Flu/Bu Busulfan 25 22 0 0 22

Flu/Cy/TBI Fludarabine 6 0 2 2 0Flu/Cy/TBI Cyclophosphamide 6 2 0 0 2Melphalan

140 Melphalan 26 1* 15 15 0Melphalan

200 Melphalan 19 0 11 11 0

Totals219 50 83 96 37*error in BSA calculation

Some regimen specific differences in Some regimen specific differences in time to engraftment between the two time to engraftment between the two groups.groups.

PossiblePossible some differences in relapse and some differences in relapse and survivor ratessurvivor rates

Numbers are not enough in each group Numbers are not enough in each group to be to be statisticallystatistically significant significant

The calculator supports consistent and The calculator supports consistent and accurate regimen dosing that follows accurate regimen dosing that follows the latest ASBMT recommendations.the latest ASBMT recommendations.

There may be someThere may be some Possible Possible clinical clinical benefit to strictly following the ASBMT benefit to strictly following the ASBMT recommendationsrecommendations

Kimberly Loftus Transplant Coordinator RWMC

Alejandro Carvajal, MD RWMC

Todd Roberts MD Medical Director of BMT RWMC

1. Which of the following statements is not true about BMT Conditioning Regimens?

A. Dose adjustments are always done using the same method, regardless of the drug being used.

B. When Adjusted Ideal Body Weight is used it is the AIBW25.

C. BMT conditioning regimen calculations can be complex.

D. The intensity of therapy is important to patient outcomes

2. True or False: Using the calculator improves dosing accuracy and may improve outcomes.

1. Which of the following statements is not true about BMT Conditioning Regimens?

A. Dose adjustments are always done using the same method, regardless of the drug being used.

B. When Adjusted Ideal Body Weight is used it is the AIBW25.

C. BMT conditioning regimen calculations can be complex.

D. The intensity of therapy is important to patient outcomes

2. True or False: Using the calculator improves dosing accuracy and may improve outcomes.