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Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia - Medical Clinic... of 21

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Hematopoietic Cell Transplantation for ChronicMyelogenous Leukemia

Policy His tory

Last Review

11/16/2017

Effective: 11/21/2003

Next

Review: 07/12/2018

Review History

Definitions

A dditiona l In form at ion

Clinical Policy

Bulletin Notes

Number: 0674 *Please see amendment for Pennsylvania Medicaid at the end of this CPB.

Policy

Aetna considers allogeneic hematopoietic cell

transplantation medically necessary for the treatment of

chronic myelogenous leukemia (CML) when the member

meets the transplanting institution's written eligibility criteria. In

the absence of such criteria, Aetna considers allogeneic

hematopoietic cell transplantation medically necessary for the

treatment of members with CML who have failed to respond to,

who have developed resistance to, or who are intolerant to

tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) for

persons without serious organ dysfunction based on the

transplanting institution's evaluation.

Aetna considers autologous hematopoietic cell transplantation

(auto BM/PSCT) experimental and investigational for the

treatment of CML under all circumstances because its

effectiveness for this indication has not been established.

http://aetnet.aetna.com/mpa/cpb/600_699/0674.html 10/29/2018

http://aetnet.aetna.com/mpa/cpb/600_699/0674.html

https://www.aetna.com/


See also CPB 0404 - Interferons

(../400_499/0404.html) CPB 0634 - Non-myeloablative

Hematopoietic Cell Transplantation (Mini-Allograft /

Reduced Intensity

, Conditioning Transplant) (0634.html)

, CPB 0638 - Donor Lymphocyte Infusion (0638.html),

CPB 0640 - Hematopoietic Cell Transplantation for Selected

and Leukemias (0640.html)

.

Background

Chronic Myelogenous Leukemia:

Chronic myelogenous leukemia (CML) is a hematologic

malignancy associated with a specific chromosomal

abnormality in the form of the Philadelphia chromosome (Ph).

This Ph abnormality represents a reciprocal balanced

translocation between the long arms of chromosomes 9 and

22, and produces the BCR–ABL fusion gene, which leads to

the expression of an abnormal protein. The resulting chimeric

protein is known as p210BCR–ABL, which is characterized by

constitutive activation of its tyrosine kinase activity. At

diagnosis, the Ph can be detected in about 95 % of patients

with CML. The incidence of CML is 1 to 2 cases per 100,000

per year. Chronic myelogenous leukemia accounts for

approximately 15 % of all leukemias and 7 % to 20 % of all

adult leukemias. Although CML can occur at any age, it most

often appears in adults with a median age of 45.

A hallmark of CML is the over-production of granulocytes.

Clinically, CML is characterized by an initial chronic or stable

phase lasting a median of 3 years. During this phase there is

a disordered maturation and excessive proliferation of myeloid

cells. Clinical manifestations that appear during the chronic

phase can usually be controlled with cytotoxic drugs or splenic

irradiation, however true remissions are rare and for the most

part the marrow remains predominantly populated with

leukemic cells. The chronic phase typically transforms into an




acute phase, known as a blast phase or crisis, which is usually

terminal. In many patients the blast phase is preceded by an

accelerated phase characterized by progression of symptoms

and resistance to treatment. Conventional chemotherapy

(e.g., busulfan, and other alkylating agents such as

cyclophosphamide and anti-metabolites) used for chronic

phase CML can induce multiple remissions and delay the

onset of blast phase to a median of 4 to 6 years.

Until recently, treatment options for patients with CML, in

addition to conventional chemotherapy, include interferon-

based therapies or allogeneic bone marrow/peripheral stem

cell transplantation (allo BM/PSCT). Treatment decisions are

generally based on the age of the patient and the phase of the

disease. Recently, several new therapies have been

developed that may change the natural history of CML and

patient prognosis. One of the new therapies is imatinib

mesylate (ST1571, Gleevec), an oral, selective BCR-ABL

kinase inhibitor that has demonstrated activity in all phases of

CML. It has been reported that imatinib produces both

hematologic and cytogenetic remission in CML patients. In

CML patients in the chronic phase, who had previously failed

interferon, imatinib induced a complete hematologic response

in 88 % and a complete cytogenetic response in 30 % of

patients. This agent has been rapidly adopted into treatment

strategies for CML. However, the response rate generally

decreases in patients with accelerated or blast phase CML.

Conventional chemotherapy during the chronic phase may

improve the patient’s quality of life, however, it does not (i)

influence the duration of the chronic phase, (ii) prevent

blastic crisis, or (iii) prolong the overall survival time.

Currently, allo BM/PSCT is considered the only potentially

curative therapy for CML. Due to the indolent nature of the

disease and the morbidity and mortality associated with BMTs,

allo BMT was initially limited to patients with CML already in

blast crisis. Although treatment with high-dose chemotherapy




(HDC), followed by allo BMT (during blast phase) induced

transient disappearance of the Ph, relapses were common and

survivals short. The somewhat disappointing results were

attributed to the advanced stage of disease and the debilitated

nature of the recipients. Subsequent attempts to perform

transplantation during the accelerated phase did result in

prolonged disease-free survival (DFS) in a small proportion of

patients. However, the incidence of relapse was high. Thus,

focus was shifted to initiating HDC and allo BMT during the

chronic phase of the disease. Results for this therapy during

the chronic phase were very encouraging. As a result,

patients are offered the option of treatment with an allo BMT

as soon as possible following initial diagnosis of chronic phase

CML, prior to evidence of disease progression.

Hehlmann and colleagues (2007) noted that early allo-PSCT

has been proposed as primary treatment modality for patients

with CML. This concept has been challenged by

transplantation mortality and improved drug therapy. In a

randomized study, primary allo-PSCT and best available drug

treatment (interferon-based) were compared in newly

diagnosed chronic phase CML patients. Assignment to

treatment strategy was by genetic randomization according to

availability of a matched related donor. Evaluation followed

the intention-to-treat principle. A total of 621 patients with

chronic phase CML were stratified for eligibility for allo-PSCT.

Three hundred and fifty four patients (62 % male; median age

of 40 years; range of 11 to 59 years) were eligible and

randomized. A total of 135 patients (38 %) had a matched-

related donor, of whom 123 (91 %) received a transplant within

a median of 10 months (range of 2 to106 months) from

diagnosis; 219 patients (62 %) had no related donor and

received best available drug treatment. With an observation

time up to 11.2 years (median of 8.9 years), survival was

superior for patients with drug treatment (p = 0.049),

superiority being most pronounced in low-risk patients (p =

0.032). The authors stated that the general recommendation




of allo-PSCT as first-line treatment option in chronic phase

CML can no longer be maintained. It should be replaced by a

trial with modern drug treatment first.

Allogeneic BM/PSCT:

High-dose chemotherapy followed by allo BM/PSCT is

currently considered the only potentially curative therapy for

CML. Studies have confirmed that patients who receive allo

BM/PSCT during the chronic phase have significantly better

survival rates than those who receive transplants during the

accelerated or blast phase.

Fyles et al (1991) reported on long-term results of allo BMT for

patients with CML (n = 70). Patients were stratified according

to risk (good risk subgroup was defined as first chronic phase

CML; poor risk subgroup was defined as other than first

chronic phase CML), as well as diagnosis. The median follow-

up was 67 months with a range of 33 to 120 months.

According to the authors, the most important factor that

determined the outcome in this patient population was disease

status at the time of BMT. The effect of risk status was

evaluated separately for each diagnosis. Good risk patients

with CML had a 5-year event-free survival (EFS) of 43 %, as

compared to the poor risk patients who had only a 15 %

chance of DFS over the same time interval. Patients with CML

in first chronic phase showed a significantly better long-term

EFS than patients transplanted with more advanced disease.

The effect of risk status was also evaluated for each diagnostic

subgroup. Patients with CML in the good risk category

relapsed significantly less frequently at 5 years than poor risk

patients: 13 % versus 58 %. Sixteen patients with CML

relapsed. A hematologic relapse was noted in 14 of these 16

recipients. All 14 were in the poor risk category and eleven of

the 14 poor risk recipients have died from their disease. The

remaining 2 patients (categorized as good risk) relapsed

cytogenetically only. Both of these patients were treated with




interferon and have subsequently become Ph negative. The

authors concluded that in order to achieve the best results,

patients should be transplanted early in their disease.

Wagner et al (1992) described results of a retrospective study

evaluating the efficacy of HDC and total body irradiation

followed by allo BMT in patients with chronic phase CML (n =

75). Patients were classified into groups according to age and

graft-versus-host disease (GVHD) prophylaxis. Groups were

defined as follows: Group 1 -- patients less than 30 years of

age receiving immunosuppressive therapy and unmanipulated

bone marrow; Group 2 -- patients 30 years of age or over

receiving immunosuppressive therapy and unmanipulated

bone marrow; Group 3 -- patients 30 years of age or over

receiving lymphocyte-depleted bone marrow plus

immunosuppressive therapy. Survival rate at 4.5 years was 52

%. When classified by age and GVHD prophylaxis, the

actuarial survival was 65 % in Group 1, 33 % in Group 2, and

38 % in Group 3. In uni-variate analysis, patients age 30

years and over, and the use of lymphocyte-depleted bone

marrow negatively influenced EFS. Thirty-seven of the 79

patients died following BMT. The principal causes of treatment

failure were acute and chronic GVHD and disease relapse.

According to the authors, results of the study confirm previous

reports that allo BMT for CML in chronic phase improves

survival in over 50 % of the patients. In addition, the authors

recommended that for patients aged 55 or younger with CML

in the chronic phase, allo BMT should be considered early

after disease presentation.

Gratwohl and co-workers (1993) conducted a retrospective

analysis on data collected by the European Bone Marrow

Transplantation Group since 1979. A total of 1,480 BMTs for

CML were done between 1979 and 1990. Of these, 1,082

patients were transplanted in first chronic phase, 88 in a

subsequent chronic phase, 251 in accelerated phase and 59 in

blast crisis. For these 4 disease stages leukemia-free survival

at 5 years was 39 %, 22 %, 22 % and 0 %, respectively. A




more detailed analysis was done on 947 patients who received

transplants in the first chronic phase from an human leukocyte

antigen (HLA)-identical sibling. There were 526 patients alive

2 to 10 years after transplant, 409 have died and 12 were lost

to follow-up. The great majority who died, 350 patients, had a

transplant-related death, while 59 patients died with or due to

relapsed disease. Of the 526 patients alive, 428 were alive

without any signs of relapse, 98 were alive with relapse. This

meant a total of 157 patients relapsed. The probability of

staying alive without relapse at 8 years was 34 %. Since not

all patients with relapse have died, actual survival is better and

the probability of being alive for the whole group was 47 % at 8

years. This long-term analysis allowed a few conclusions: (i)

patients with CML in blastic transformation should not be

considered routine candidates for BMT; (ii) BMT should be

carried out as soon after diagnosis as possible if an HLA-

identical sibling is available; and (iii) age, donor/recipient

sex combination, time span from diagnosis to transplant

and initial disease status influence outcome.

The National Comprehensive Cancer Network’s practice

guidelines on CML (2003) states that 3 effective modalities are

currently available for the primary management of CML: (i)

allo-BMT, (ii) interferon alpha with or without cytarabine,

and (iii) imatinib mesylate. Moreover, in a recent review on

therapeutic strategies for the treatment of CML, Garcia-

Manero et al (2003) stated that allo-PSCT is curative in

selected patients, and is most effective when carried out

during the chronic phase of disease. For patients with a high-

predicted risk of disease recurrence (e.g., transplantation in

accelerated-blastic phase) after allo-PSCT, preventive post-

allo-PSCT maintenance measures such as interferon alpha or

imatinib may be beneficial.




Guidelines from the British Society of Haematology on

CML (Goldman, 2007) state that allogeneic stem cell

transplantation may be considered for patients with suitable

donors as an alternative to a second generation tyrosine

kinase inhibitor or if they fail such treatment.

Guidelines from Cancer Care Ontario (Imrie et al, 2009) state

that allogeneic stem cell transplantation is an option for

patients with CML for whom medical therapy has failed, as well

as those in accelerated phase or blast crisis.

Chalandon et al (2014) noted that patients with CML relapsing

after allogeneic stem cell transplantation may be treated by

tyrosine kinase inhibitors and/or by donor lymphocyte

infusions. Best strategies and timing of administration of

lymphocytes are unclear. These investigators analyzed 155

patients who relapsed after allogeneic stem cell

transplantation for CML with disease detectable only by

molecular methods and who subsequently received

lymphocytes. Transplants were performed in first chronic

phase (n = 125) or in advanced disease (n = 29) from identical

siblings (n = 84) or unrelated donors (n = 71) between 1986

and 2003. They received lymphocytes either during molecular

relapse (n = 85) or upon progression to more advanced

disease between 1993 and 2004. The median interval from

relapse to lymphocytes infusion was 210 (0 to 1,673) days.

The median follow-up after it was 46 (3 to 135) months.

Overall survival was 76 ± 4 % at 5 years after lymphocyte

infusions (89 ± 8 % with sibling donors and 63 ± 13 % with

unrelated donors (p = 0.003)). Survival was 69 ± 14 % if

lymphocytes were given within 6 months of the detection of

molecular relapse and 81 ± 10 % (p = 0.061) if given later; 81

± 11 % if given at molecular relapse versus 71 ± 12 % (p =

0.26) with more advanced disease. In multi-variate analysis

survival was worse if the donor was unrelated (HR 2.54 (95 %

confidence interval [CI]: 1.15 to 5.53), p = 0.021) and better

with lymphocyte infusion beyond 6 months from molecular

relapse (HR 0.4 (95 % CI: 0.19 to 0.84), p = 0.0.018). These




data confirmed the remarkable effectiveness of lymphocyte

infusion for this disease. The authors concluded that there

appears to be no advantage of administering it early upon

detection of molecular relapse in patients who received

allogeneic stem cell transplantation for CML.

Kitanaka (2016) noted that the introduction of tyrosine kinase

inhibitors (TKIs) has dramatically changed the management of

patients with CML. Despite improved outcomes for most CML

patients, disease progression from chronic phase (CP) to

accelerated phase (AP) or blast phase (BP) occurs in 1 to 1.5

% of cases per year with current TKI therapy. In addition,

about 10 to 15 % of newly diagnosed patients present in AP or

BP. Even in the TKI era, the prognosis of patients with CML-

AP is not satisfactory. Although de-novo AP patients who

respond optimally to TKI have excellent outcomes, the

prognosis of the remaining CML –AP patients treated with TKI

remains poor. For CML-AP patients, allogeneic stem cell

transplantation (allo-HSCT) is the only curative therapy.

Patients eligible for allo-HSCT should first be treated with TKI

with or without chemotherapy, in order to obtain reversion to

CP, followed promptly by allo-HSCT. The author concluded

that the survival rates of patients undergoing allo-HSCT for

CML-AP are still disappointing; prophylactic or pre-emptive

use of TKIs after allo-HSCT may improve long-term survival.

They stated that further investigation to improve the treatment

outcomes of patients with CML-AP is needed.

Shulman and associates (2016) stated that the management

of CML in children changed dramatically with the introduction

of TKIs. Unfortunately, outcomes for patients presenting in an

advanced stage (AP- or BP-CML) continues to be poor,

requiring chemotherapy and all-HSCT to attempt cure.

Integration of TKIs in the therapy of advanced CML is still an

area of active investigation. There are little published data on

TKI use in children with advanced stage CML. These

researchers performed a retrospective review of all children

treated at their institution between January 1, 2010 and June



Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia -Medical Cli... of 21

30, 2013, and identified 5 children, aged 12 to 18 years, with

advanced stage CML. All patients were treated with a TKI

before allo-HSCT and TKIs were re-started following allo-

HSCT in 4/5 with a goal of continuing until 2 years post-

transplant. At time of allo-HSCT, all were in a morphologic

and cytogenetic remission; 1 patient had also achieved

molecular remission. All patients were alive and in molecular

remission at an average of 38 months (range of 14 to 51

months) following transplant. The authors concluded that their

experience indicated that TKIs were safe and well-tolerated in

children both pre-transplant and post-transplant and may

improve outcomes in this aggressivedisease.

Londo and colleagues (2017) noted that TKIs are widely used

to treat patients with CML-CP, and outcomes of TKI treatment

for patients with CML-CP have been excellent. Since multiple

TKIs are currently available, 2nd-line or 3rd-line TKI therapy is

considered for patients who are intolerant of or resistant to the

previous TKI treatment. Thus, allo-HSCT is considered only

for patients with disease progression or for patients after

treatment failure with multiple TKIs. To reflect the current

clinical situation of patients with CML-CP, these investigators

examined if prior TKI treatment affects the outcome of allo-

HSCT. Data from 237 patients for whom the number of pre-

transplant TKIs varied from 1 to 3 were used for analysis.

Before allo-HSCT, 153 patients were treated with 1 TKI, 49

patients were treated with 2 TKIs, and 35 patients were treated

with 3 TKIs. In addition to conventional risk factors, i.e.,

disease status at transplantation and patient's age, the use of

3 TKIs before transplantation was identified as a significant

adverse factor for prognosis. Non-relapse mortality rate was

higher in patients treated with 3 TKIs than in patients treated

with 1 or 2 TKIs. The authors concluded that these findings

suggested that allo-HSCT could be considered for young

patients with CML-CP who manifest resistance to 2nd-line TKI

therapy and who have an appropriate donor.




Autologous BM/PSCT:

Available scientific evidence has not established autologous

bone marrow/peripheral stem cell transplantation (auto-

BM/PSCT) as an effective treatment for CML. Patient

populations varied across these studies. Some focused on

newly diagnosed patients or those in the first year since

diagnosis. Others focused on patients who did not respond to

or relapsed after initial treatment using interferon alpha.

Finally, some focused on patients transplanted in late chronic

phase or after transformation to accelerated phase or blast

crisis. Although some patients achieved complete or partial

molecular remissions and long-term DFS, these studies do not

permit conclusions free from the influence of patient selection

bias. Moreover, all autotransplanted patients included in these

reports were treated before Gleevec became available. Since

this drug has been shown to induce major hematologic and,

less often, cytogenetic remissions even among patients in

accelerated phase and blast crisis, future studies of

autotransplants for CML, may focus on patients who fail or

become resistant to imatinib mesylate. Alternatively, it may be

incorporated into combination regimens used for high dose

therapy.

Bhatia et al (1997) stated that the role of autologous

transplantation in the early therapy of CML is not yet

understood. Analysis of a first generation of autologous

transplants performed largely in previously treated, older

patients unsuitable for allogeneic transplantation or not

responding to interferon alpha therapy suggests that this

approach has anti-leukemia activity associated with

prolongation of survival and acceptable peri-transplantation

mortality. However, because these trials were uncontrolled

and patient selection could have contributed to the longer than

expected survival, controlled studies are needed to confirm the

encouraging findings of these early reports and determine if

autologous transplantation prolongs survival.




Podesta et al (2000) examined changes that occur in the

percentage of Ph-negative- and Ph-positive-committed

progenitor cells and ascertained the relationship between

changes and clinical outcome in 15 patients with CML who

were autografted soon after diagnosis with 85 % to 100 % Ph-

negative peripheral blood progenitor cells (PBPC). The

authors reported that a prolonged period of complete or almost

complete Ph-negative hemopoiesis was achieved in patients

with CML who underwent autografting with Ph-negative

progenitors. These researchers stated that longer follow-up

studies are needed to evaluate whether these changes are

associated with improved survival.

Michallet et al (2000) reported data on 28 CML patients

autotransplanted in chronic phase with PBPC mobilized with

G-CSF (5 ug/kg/day for 5 days) given subcutaneously while

continuing interferon alpha therapy. The authors concluded

that the results of this strategy were encouraging in poor

interferon alpha responders, however, other prospective

studies that try to maintain the cytogenetic responses obtained

immediately after transplantation are needed.

Meloni and associates (2001) stated that the potential role of

auto-SCT as an alternative therapeutic strategy in CML has

been widely explored in pilot studies, but the clinical results in

terms of survival have so far been evaluated only

retrospectively and in heterogeneous groups of patients.

These investigators evaluated the feasibility and long-term

efficacy of unmanipulated auto-SCT followed by low dose

interferon alpha in a homogeneous group of patients affected

by CML in a very early phase of disease (n = 26). The authors

concluded that high dose therapy followed by unmanipulated

peripheral blood stem cell transplantation and low-dose

interferon alpha is a feasible approach, which results in long-

term survival in newly diagnosed CML patients. However,

these findings need to be confirmed in controlled trials




comparing auto-SCT with other therapeutic approaches, such

as the use of interferon alpha alone or in combination with

other agents.

Koziner et al (2002) evaluated the role of auto-SCT in

prolonging DFS and overall survival (OS) in patients with CML

who received autografts of Ph-positive or Ph-negative cell

harvests (n = 53). The authors found that auto-SCT with Ph-

negative cell harvests after myeloablative chemotherapy

resulted in prolonged periods of hematologic and cytogenetic

remission or stable disease after cytogenetic/molecular

recurrence in some patients with CML. A superior DFS was

observed without any benefit observed for OS. These

investigators concluded that auto-SCT with Ph-negative cells

is a promising procedure because it can improve the DFS

probability of patients who are unsuitable for allo-SCT from a

histo-identical sibling.

The National Comprehensive Cancer Network’s practice

guidelines on CML (2009) as well as a recent review on

therapeutic strategies for the treatment of CML did not discuss

the use of autologous transplantation as a treatment option

(Garcia-Manero et al, 2003). Schiffer and colleagues (2003)

stated that auto-SCT following intense chemoradiotherapy

may prolong survival and reduce complications and mortality

during peri-transplantation in patients with CML, however, this

procedure is not curative. The collection of stem cells when

the patient is in complete cytogenetic response for use in case

of relapse is considered an investigative procedure.

A meta-analysis of 6 randomized studies (CML Autograft Trials

Collaboration, 2007) reported that the results do not suggest a

role for auto-SCT in initial treatment for CML, but it may still

merit investigation in patients resistant to tyrosine kinase

inhibitors.




Guidelines from Cancer Care Ontario (Imrie, et al., 2009) state

that autologous stem cell transplantation is not recommended

for patients with CML.

A ppendix

The Hematopoietic Cell Transplantion-Specific

Comorbidity Score Calculator is available at the following

website:

Calculate by QxMD (http://www.qxmd.com/calculate

online/hematology/hct-ci)

.

CPT Codes / HCPCS Codes / ICD-10 Codes

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

Code Code Description

CPT codes covered if selection criteria are met:

38230 Bone marrow harvesting for transplantation;

allogenic

38240 Hematopoietic progenitor cell (HPC); allogeneic

transplantation per donor

38242 Allogeneic lymphocyte infusions

CPT codes not covered for indications listed in the CPB:

38206 Blood-derived hematopoietic progenitor cell

harvesting for transplantation, per collection;

autologous

38232 autologus

38241 Hematopoietic progenitor cell (HPC);

autologous transplantation

Other CPT codes related to the CPB:



http://www.qxmd.com/calculate-

http://www.qxmd.com/calculate-online/hematology/hct-ci

http://www.qxmd.com/calculate-online/hematology/hct-ci


Code Code Description

38204 -

38215

Bone Marrow or Stem Cell Services/Procedures

HCPCS codes covered if selection criteria are met::

S2150 Bone marrow or blood-derived stem cells

(peripheral or umbilical), allogeneic or

autologous, harvesting, transplantation, and

related complications; including: pheresis and

cell preparation/storage; marrow ablative

therapy; drugs, supplies, hospitalization with

outpatient follow-up; medical/surgical,

diagnostic, emergency, and rehabilitative

services; and the number of days of pre- and

post-trasnplant care in the global definition

Other HCPCS codes related to the CPB:

S0088 Imatinib, 100mg

ICD-10 codes covered if selection criteria are met:

C92.10 -

C92.11

Chronic myeloid leukemia

The above policy is based on the following references:

Allogeneic Bone Marrow Transplantation:

1. Fyles G, Messner HA, Lockwood G, et al. Long-term

results of bone marrow transplantation for patients

with AML, ALL, CML prepared with single dose total

body irradiation of 500cGy delivered with a high dose

rate. Bone Marrow Transplant. 1991;8(6):453-463.

2. Wagner J, Zahurak M, Piantadosi S, et al. Bone marrow

transplantation of chronic myelogenous leukemia in




chronic phase: Evaluation of risks and benefits. J Clin

Oncol. 1992;10(5) :779-789.

3. Gratwohl A, Hermans J, Niederwieser D, et al. Bone

marrow transplantation for chronic myeloid leukemia:

Long term results. Chronic Leukemia Working Party of

the European Group for Bone Marrow

Transplantation. Bone Marrow Transplant. 1993;12

(5):509-516.

4. Silver RT, Woolf SH, Hehlmann R, et al. An evidence-

based analysis of the effect of busulfan, hydroxyurea,

interferon and allogeneic bone marrow

transplantation in treating the chronic phase of

chronic myeloid leukemia: Developed for the American

Society of Hematology. Blood. 1999;94(5):1517-1536.

5. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety

of a specific inhibitor of the BCR-ABL tyrosine kinase in

chronic myeloid leukemia. N Eng J Med. 2001;344

(14):1031-1037.

6. Goldman JM, Melo JV. Targeting the BCR-ABL tyrosine

kinase in chronic myeloid leukemia. N Engl J Med.

2001;344(14):1084-1086.

7. Weisdorf DJ, Anasetti C, Antin JH, et al. Allogeneic bone

marrow transplantation for chronic myelogenous

leukemia: Comparative analysis of unrelated versus

matched sibling donor transplantation. Blood. 2002;99

(6):1971-1977.

8. O'Dwyer ME, Mauro MJ, Druker BJ. Recent

advancements in the treatment of chronic

myelogenous leukemia. Ann Rev Med. 2002;53:369

381.

9. Garcia-Manero G, Talpaz M, Kantarjian HM. Current

therapy of chronic myelogenous leukemia. Intern Med.

2002;41(4):254-264.

10. Novartis Oncology. Gleevec (imatinib mesylate).

Prescribing Information. East Hanover, NJ: Novartis;

January 2002.




11. Aetna Inc. Protein kinase inhibitors -- Gleevec.

Pharmacy Clinical Policy Bulletins. Hartford, CT: Aetna;

January 1, 2005.

12. Garcia-Manero G, Faderl S, O'Brien S, et al. Chronic

myelogenous leukemia: A review and update of

therapeutic strategies. Cancer. 2003;98(3):437-457.

13. Dalziel K, Round A, Stein K, et al. Effectiveness and

cost-effectiveness of imatinib for first-line treatment of

chronic myeloid leukaemia in chronic phase: a

systematic review and economic analysis. Health

Technology Assess. 2004;8(28):1-134.

14. Oehler VG, Radich JP, Storer B, et al. Randomized trial

of allogeneic related bone marrow transplantation

versus peripheral blood stem cell transplantation for

chronic myeloid leukemia. Biol Blood Marrow

Transplant. 2005;11(2):85-92.

15. Bornhauser M, Kroger N, Schwerdtfeger R, et al.

Allogeneic haematopoietic cell transplantation for

chronic myelogenous leukaemia in the era of imatinib:

A retrospective multicentre study. Eur J Haematol.

2006;76(1):9-17.

16. Greenberg PL, Baer MR, Bennett JM, et al.

Myelodysplastic syndromes clinical practice guidelines

in oncology. J Natl Compr Canc Netw. 2006;4(1):58-77.

17. Hehlmann R, Berger U, Pfirrmann M, et al. Drug

treatment is superior to allografting as first-line

therapy in chronic myeloid leukemia. Blood. 2007;109

(11):4686-4692.

18. Hehlmann R, Hochhaus A, Baccarani M; European

LeukemiaNet. Chronic myeloid leukaemia. Lancet.

2007;370(9584):342-350.

19. Goldman J. Recommendations for the management of

BCR-ABL-positive chronic myeloid leukaemia. London,

UK: British Committee for Standards in Haematology;

2007.




20. National Comprehensive Cancer Network (NCCN).

Chronic myelogenous leukemia. NCCN Clinical Practice

Guidelines in Oncology. Jenkintown, PA: NCCN; 2009.

21. Gratwohl A, Heim D. Current role of stem cell

transplantation in chronic myeloid leukaemia. Best

Pract Res Clin Haematol. 2009;22(3):431-443.

22. Champlin R, de Lima M, Kebriaei P, et al.

Nonmyeloablative allogeneic stem cell transplantation

for chronic myelogenous leukemia in the imatinib era.

Clin Lymphoma Myeloma. 2009;9 Suppl 3:S261-S265.

23. Baccarani M, Cortes J, Pane F, et al; European

LeukemiaNet. Chronic myeloid leukemia: An update of

concepts and management recommendations of

European LeukemiaNet. J Clin Oncol. 2009;27 (35):6041

6051.

24. Sun YQ, Xu LP, Liu DH, et al. Allogeneic hematopoietic

stem cell transplantation for chronic myelomonocytic

leukemia: A report of 12 patients. Zhonghua Xue Ye

Xue Za Zhi. 2013;34(2):113-116.

25. Chalandon Y, Passweg JR, Guglielmi C, et al. Early

administration of donor lymphocyte infusions upon

molecular relapse after allogeneic hematopoietic stem

cell transplantation for chronic myeloid leukemia: A

study by the Chronic Malignancies Working Party of

the EBMT. Haematologica. 2014;99(9):1492-1498.

26. Baccarani M, Castagnetti F, Gugliotta G, Rosti G. A

review of the European LeukemiaNet

recommendations for the management of CML. Ann

Hematol. 2015;94 Suppl 2:S141-S147.

27. Shimoni A, Volchek Y, Koren-Michowitz M, et al. Phase

1/2 study of nilotinib prophylaxis after allogeneic stem

cell transplantation in patients with advanced chronic

myeloid leukemia or Philadelphia chromosome-

positive acute lymphoblastic leukemia. Cancer.

2015;121(6):863-871.




28. Kitanaka A. Management of advanced-phase chronic

myeloid leukemia. Rinsho Ketsueki. 2016;57(10):1962

1971.

29. Shulman DS, Lee MA, Lehmann LE, Margossian SP.

Outcomes following bone marrow transplantation in

children with accelerated phase or blast crisis chronic

myelogenous leukemia in the era of tyrosine kinase

inhibitors. J Pediatr Hematol Oncol. 2016;38(8):610

614.

30. Ozen M, Ustun C, Oztürk B, et al. Allogeneic

transplantation in chronic myeloid leukemia and the

effect of tyrosine kinase inhibitors on survival: A quasi-

experimental study. Turk J Haematol. 2017;34(1):16-26.

31. Kondo T, Nagamura-Inoue T, Tojo A, et al. Clinical

impact of pre-transplant use of multiple tyrosine

kinase inhibitors on the outcome of allo-HSCT for CML.

Am J Hematol. 2017 May 20 [Epub ahead of print].

Autologous Bone Marrow Transplantation:

1. Bhatia R, Verfaillie CM, Miller JS, McGlave PB.

Autologous transplantation therapy for chronic

myelogenous leukemia. Blood. 1997;89(8):2623-2634.

2. Boiron JM, Cahn JY, Meloni G, et al. Chronic myeloid

leukemia in first chronic phase not responding to

alpha-interferon: Outcome and prognostic factors

after autologous transplantation. EBMT Working Party

on Chronic Leukemias. Bone Marrow Transplant.

1999;24(3):259-264.

3. Pigneux A, Faberes C, Boiron JM, et al. Autologous

stem cell transplantation in chronic myeloid leukemia:

A single center experience. Bone Marrow Transplant.

1999;24(3):265-270.

4. Podesta M, Piaggio G, Sessarego M, et al. Autografting

with Ph-negative progenitors in patients at diagnosis

of chronic myeloid leukemia induces a prolonged




prevalence of Ph-negative hemopoiesis. Exp Hematol.

2000;28(2):210-215.

5. McBride NC, Cavenagh JD, Newland AC, et al.

Autologous transplantation with Philadelphia-negative

progenitor cells for patients with chronic myeloid

leukaemia (CML) failing to attain a cytogenetic

response to alpha interferon. Bone Marrow

Transplant. 2000;26(11):1165-1172.

6. Michallet M, Thiebaut A, Philip I, et al. Late autologous

transplantation in chronic myelogenous leukemia with

peripheral progenitor cells mobilized by G-CSF and

interferon-alpha. Leukemia. 2000;14(12):2064-2069.

7. Meloni G, Capria S, Vignetti M, et al. Ten-year follow-up

of a single center prospective trial of unmanipulated

peripheral blood stem cell autograft and interferon-

alpha in early phase chronic myeloid leukemia.

Haematologica. 2001;86(6):596-601.

8. Koziner B, Dengra C, Lucero G, et al. Autologous stem

cell transplantation for patients with chronic myeloid

leukemia. The Argentine Group of Bone Marrow

Transplantation (GATMO) experience. Cancer. 2002;95

(11):2339-2345.

9. Schiffer CA, Hehlmann R, Larson R. Perspectives on the

treatment of chronic phase and advanced phase CML

and Philadelphia chromosome positive ALL(1).

Leukemia. 2003;17(4):691-699.

10. Bhatia R, McGlave PB. Autologous hematopoietic cell

transplantation for chronic myelogenous leukemia.

Hematol Oncol Clin North Am. 2004;18(3):715-732, xi.

11. CML Autograft Trials Collaboration. Autologous stem

cell transplantation in chronic myeloid leukaemia: A

meta-analysis of six randomized trials. Cancer Treat

Rev. 2007;33(1):39-47.

12. Imrie K, Rumble RB, Crump M; Advisory Panel on Bone

Marrow and Stem Cell Transplantation; Hematology

Disease Site Group of Cancer Care Ontario Program in

Evidence-based Care. Stem cell transplantation in




adults. Recommendation Report. Toronto, ON: Cancer

Care Ontario; 2009.




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subject to change.

Copyright © 2001-2018 Aetna Inc.



AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical Policy Bulletin Number:

0674 Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia

There are no amendments for Medicaid.

www.aetnabetterhealth.com/pennsylvania Updated 11/16/2017

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