Medical Policies - Surgery

Hematopoietic Stem-Cell Transplantation for Chronic Myelogenous Leukemia (CML)


Effective Date:07-15-2018



Allogeneic hematopoietic stem-cell transplantation (HSCT) may be considered medically necessary to treat chronic myelogenous leukemia (CML).

Autologous HSCT is considered experimental, investigational and/or unproven as a treatment of CML.

NOTE 1: See Medical Policy SUR703.002 Hematopoietic Stem-Cell Transplantation (HSCT) or Additional Infusion Following Preparative Regimens (General Donor and Recipient Information) for detailed, descriptive information on HSCT related services.


Hematopoietic Stem-Cell Transplantation (HSCT)

HSCT refers to a procedure in which hematopoietic stem-cells are infused to restore bone marrow function in patients who receive bone-marrow-toxic doses of cytotoxic drugs with or without whole body radiation therapy. Hematopoietic stem-cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem-cells in it are antigenically “naive” and thus, are associated with a lower incidence of rejection or graft-versus-host disease (GVHD).

Immunologic compatibility between infused hematopoietic stem-cells and the recipient is not an issue in autologous HSCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic HSCT. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the class I and class II loci on chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci (with the exception of umbilical cord blood).

Chronic Myelogenous Leukemia (CML)

CML is a hematopoietic stem-cell disorder that is characterized by the presence of a chromosomal abnormality called the Philadelphia (Ph) chromosome, which results from reciprocal translocation between the long arms of chromosomes 9 and 22. This cytogenetic change results in constitutive activation of BCR-ABL, a tyrosine kinase (TK) that stimulates unregulated cell proliferation, inhibits cell apoptosis, creates genetic instability, and upsets interactions between CML cells and the bone marrow stroma only in malignant cells. CML accounts for about 15% of newly diagnosed cases of leukemia in adults and occurs in about 1 to 2 cases per 100,000 adults. (1)

The natural history of the disease consists of an initial (indolent) chronic phase, lasting a median of 3 years, which typically transforms into an accelerated phase, followed by a “blast crisis,” which is usually the terminal event. Most patients present in chronic phase, often with nonspecific symptoms that are secondary to anemia and splenomegaly. CML diagnosis is based on the presence of the Ph chromosome abnormality by routine cytogenetics, or by detection of abnormal BCR-ABL products by fluorescence in situ hybridization (FISH) or molecular studies, in the setting of persistent unexplained leukocytosis. Conventional-dose chemotherapy regimens used for chronic phase disease can induce multiple remissions and delay the onset of blast crisis to a median of 4 to 6 years. However, successive remissions are invariably shorter and more difficult to achieve than their predecessors.


Historically, the only curative therapy for CML in blast phase was allogeneic hematopoietic stem-cell transplantation (HSCT), which was used more widely earlier in the disease process given the lack of other therapies for chronic phase CML. Drug therapies for chronic phase CML were limited to nonspecific agents including busulfan, hydroxyurea, and interferon-α. (1)

Imatinib mesylate (Gleevec®), a selective inhibitor of the abnormal BCR-ABL tyrosine kinase (TK) protein, is considered the treatment of choice for newly diagnosed CML. While imatinib can be highly effective in suppressing CML, it is not curative and is ineffective in 20% to 30% of patients, initially or due to development of BCR-ABL mutations that cause resistance to the drug. Even so, the overall survival (OS) of patients who present in chronic phase is greater than 95% at 2 years and 80% to 90% at 5 years. (2)

For CML, 2 other TK inhibitors (TKIs; dasatinib, nilotinib) have received marketing approval from the U.S. Food and Drug Administration (FDA) as front-line therapy or following failure or patient intolerance of imatinib. Two additional TKIs (bosutinib and ponatinib) have been approved for use in patients resistant or intolerant to prior therapy.

For patients on imatinib who have disease progression, the therapeutic options include increasing the imatinib dose, changing to another TKI, or allogeneic HSCT. Detection of BCR-ABL variants may be important in determining an alternative TKI; the presence of T315I variant is associated with resistance to all TKIs and should indicate the need for allogeneic HSCT or an experimental therapy. TKIs have been associated with long-term remissions; however, if disease progression occurs on TKI therapy, allogeneic HSCT is generally indicated and offers the potential for cure.

Regulatory Status

The U.S. Food and Drug Administration (FDA) regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. (3) Hematopoietic stem-cells are included in these regulations.


This policy was originally created in 1990, moved to this policy in 2010. The policy has been updated with reviews of the MedLine database. The most recent literature review was performed through June 2018. While the coverage of this policy does not address myeloablative (MA) (also known as high-dose chemotherapy [HDC]) or reduced intensity conditioning (RIC) prior to hematopoietic stem-cell transplantation (HSCT), discussion of HSCT outcomes may be influenced by the type of preparative conditioning completed prior to the transplantation. The following is a summary of the key literature to date for preparative conditioning, allogeneic or autologous HSCT.

Medical policies assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function - including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Allogeneic HSCT

In the pre-tyrosine kinase inhibitor (TKI) era, allogeneic HSCT was the standard of care for chronic myeloid leukemia (CML). Evidence in support of allogeneic HSCT includes a 2015 RCT comparing primary HSCT from a matched family donor (n=166) with best available drug treatment (n=261), which enrolled patients from 1997 to 2004. (4) There were no differences in 10-year overall survival (OS) between groups (0.76 for HSCT patients versus 0.69 for drug treatment patients). Those with low transplant risk treated with HSCT had improved survival compared with those treated with medical therapy, but, after patients entered blast crisis, survival did not differ between groups.

The advent of TKI therapy has altered the treatment paradigm for CML such that most patients are treated initially with a TKI until the disease progresses. While progression may occur within months of starting a TKI, progression may be delayed for years, as shown by the results of the IRIS trial (5) and other studies. (6, 7) With the addition of 3 other TKIs (nilotinib, dasatinib, bosutinib) plus the possibility of effective dose escalation with imatinib to override resistance, it is possible to maintain a typical CML patient past the upper age limit (usually 50-55 years) at which a myeloablative allogeneic HSCT is considered an option. (5, 8, 9)

Nonrandomized Studies

Several nonrandomized studies have compared treatment using TKI therapy with allogeneic HSCT in CML patients. Liu et al. (2013) evaluated outcomes for CML patients who underwent HSCT after imatinib failure. (10) They retrospectively evaluated 105 patients with newly diagnosed chronic phase CML seen at a single institution from 1999 to 2011. Sixty-six patients received first-line imatinib therapy, 26 (treated before 2003) received interferon followed by imatinib, and 13 received first-line allogeneic HSCT with curative intent. Twenty-two (21%) patients received allogeneic HSCT overall, including 13 as first-line therapy and 9 following imatinib failure. Compared with those who received first-line allogeneic HSCT, those who underwent HSCT following imatinib failure had higher European Group for Blood and Marrow Transplantation (EBMT) risk score (p=0.03). Among those receiving allogeneic HSCT (n=22; median follow-up, 134 months; range, 6-167 months), patients with imatinib failure and disease progression had a significantly worse OS (p=0.015) compared with those receiving allogeneic HSCT as first-line therapy. Patients receiving first-line allogeneic HSCT had a 3-year OS rate of 91.7% (95% confidence interval [CI], 29 to 38 months); 1 patient in this group died of relapse and 1 of chronic graft-versus-host disease (GVHD).

Xu et al. (2015) retrospectively compared second-generation TKI therapy with allogeneic HSCT in 93 patients in accelerated-phase CML. (11) The second-generation TKI therapy group included 33 subjects, most of whom had been previously treated with another TKI (31 with imatinib, 2 with nilotinib). Of 60 patients treated with allogeneic HSCT, 10 were treated with HSCT for the first time, and 50 had been previously treated with imatinib. Median OS was significantly shorter with second-generation TKI treatment (22 months) than with allogeneic HSCT (82 months). Median progression-free survival and event-free survival (EFS) rates were similarly shorter with second-generation TKI treatment than with allogeneic HSCT.

Zhang et al. (2016) retrospectively compared imatinib (n=292) with allogeneic HSCT (n=141) in patients who had CML. (12) Survival rates were significantly longer in the imatinib group than in the allogeneic HSCT group: 5-year EFS rates were 84% and 75% (p<0.05) and 5-year OS rates were 92% and 79%, both respectively. Findings were similar for patients with chronic phase and advanced phase disease.

Several studies have compared outcomes for CML patients treated with allogeneic HSCT in the pre- and current TKI eras. While these studies have generally reported no worsening in treatment outcomes for allogeneic HSCT following TKI therapy, they are limited by their underlying differences in treatment regimens from different eras. In a retrospective analysis by Shen et al. (2015), of the 106 patients who underwent allogeneic HSCT and who either did (n=36) or did not (n=70) receive prior treatment with TKIs, no significant differences were reported in 10-year relapse-free survival (RFS) or OS rates. (13) However, TKI-treated patients had a higher incidence of 0.5-year transplant-related mortality. In another retrospective analysis comparing patients treated using allogeneic HSCT in the pre-TKI era (1989-2001; n=39) with those treated in the TKI era (2002-2013; n=30), Chamseddine et al. (2015) reported longer 3-year OS and leukemia-free survival among patients treated in the TKI era. (14)

Case Series

A number of case series, primarily involving a single center, have reported outcomes for patients treated with allogeneic HSCT following TKI treatment failure. In a 2015 series of 51 patients given allogeneic HSCT, 32 of whom were treated for TKI resistance or intolerance, 8-year OS and event-free survival rates were 68% and 46%, respectively. (15) Another 2015 prospective series of 28 patients who underwent allogeneic HSCT after the failure of at least 2 TKIs reported deep molecular remission in 18 subjects. (16) However, all 6 patients transplanted in blast crisis died. In a smaller series, Zhao et al. (2014) reported on outcomes for 12 patients with CML who experienced disease progression on imatinib and received dasatinib or nilotinib followed by allogeneic HSCT at a single center. (17) After a median follow-up of 28 months (range, 12-37 months) after allogeneic HSCT, 8 (66.7%) of 12 patients were alive, including 7 with complete molecular remission.

In addition to being used prior to allogeneic HSCT, TKI therapy may be used after HSCT to prevent or treat disease relapse. Egan et al. (2015) retrospectively analyzed patients at a single institution who underwent allogeneic HSCT for CML and Ph chromosome-positive acute lymphoblastic leukemia (ALL) and had detectable BCR-ABL transcripts by polymerase chain reaction (PCR), as well as RNA available for sequencing of the ABL kinase domain, in both the pre- and post-HSCT settings to evaluate the impact of pre-HSCT variants in the ABL kinase domain on post-HSCT relapse. (18) Among 95 patients with CML with available PCR transcripts, 10 (10.5%) were found to have pre-HSCT ABL kinase variants known to confer resistance to TKIs. Of those with CML, 88.4% underwent myeloablative chemotherapy, and 11.6% underwent nonmyeloablative chemotherapy. Twenty-nine CML patients received post-HSCT TKIs--19 (65.5%) for prophylaxis and 10 (34.5%) for treatment of refractory or relapsed disease. In 9 (64.2%) of the 14 patients with pre-HSCT variants (which included both CML and Ph chromosome–positive ALL), the same variants conferring TKI resistance was also detectable after allogeneic HSCT. Among the 14 with pre-HSCT variants, 8 (57.1%) received a TKI in the post-HSCT setting, and 7 (50%) demonstrated post-HSCT refractory disease or relapse. Of the 7 with relapsed disease, 6 had been given a predictably ineffective TKI within the first 100 days after allogeneic HSCT, based on variant analysis conducted by the authors.

HSCT With Nonmyeloablative Conditioning

Techniques for allogeneic HSCT have continued to develop, with important advancements in the use of nonmyeloablative or RIC preparative regimens. Overall, among 9 studies evaluated in a 2007 review, outcomes with RIC allogeneic transplants were similar to those with conventional allotransplants, with OS rates ranging from 35% at 2.5 years to 85% at 5 years among patients in chronic phase at transplant. (19) Among the studies assessed in this review, treatment-related mortality or non-relapse mortality (NRM) ranged from 0% to 29% at 1 year. In the largest retrospective study, the EBMT (2005) evaluated 186 patients. (20) The OS rate was 54% at 3 years using a variety of RIC regimens in patients in chronic phase 1 (n=118), chronic phase 2 (n=26), acute phase (n=30), and blast crisis (n=12). Among patients transplanted in the first chronic phase, the OS rate was 69% at 3 years.

RIC regimens have many of the same limitations as standard-intensity conditioning: relapse, GVHD, and mortality from treatment-related causes other than myelotoxicity. However, in the absence of prospective, comparative, randomized trials, only indirect comparisons can be made between the relative clinical benefits and harms associated with myeloablative and RIC regimens with allogeneic HSCT. Comparison of study results is further compromised by heterogeneity across patients, treatments, and outcome measures. Nonetheless, clinical evidence has suggested outcomes in CML are similar between myeloablative and RIC allogeneic HSCT. (6, 19, 20)

Section Summary: Allogeneic HSCT

Allogeneic HSCT is accepted as a standard treatment in CML, although the use of targeted TKI therapy has allowed many patients who would previously have required allogeneic HSCT to forestall or avoid transplantation altogether. Direct comparisons between myeloablative and RIC regimens are not available, but the available evidence has suggested that allogeneic HSCT following nonmyeloablative conditioning regimens can lead to short- and medium-term survival rates that are on the order of those seen after myeloablative conditioning regimens. Although research into the optimal timing of allogeneic HSCT in the setting of TKI therapy is limited, the available evidence has suggested that pretreatment with TKIs does not worsen outcomes after allogeneic HSCT and may improve outcomes.

Autologous HSCT

A major limitation in the use of autologous HSCT in patients with CML is a high probability that leukemic cells will be infused back into the patient. However, it is recognized that many CML patients still have normal marrow stem cells. Techniques used to isolate and expand this normal clone of cells have included ex vivo purging, long-term culture, and immunophenotype selection. (21) Even without such techniques, there are isolated case reports of partial cytogenetic remissions after autologous HSCT, and a 1997 study suggested that patients undergoing such therapy may have improved survival compared with historical controls. (22)

In the pre-TKI era, there was active research into the use of autologous HSCT for CML. McGlave et al. (1994) reported on outcomes for 200 consecutive autologous transplants using purged or unpurged marrow from 8 different transplant centers over 7 years. (23) Of the 200 patients studied, 125 were alive at a median follow-up of 42 months. Of the 142 transplanted in chronic phase, median survival had not been reached at the time of publication, while the median survival was 35.9 months for those transplanted during an accelerated phase. Other data consist of small, single-institution case series using a variety of techniques to enrich the population of normal stem cells among the harvested cells. (22)

Additional reports of small, uncontrolled studies with a total of 182 patients (range, 15-41 patients) given autologous HSCT for CML included patient populations that varied across the studies. Some (2000, 2001) focused on newly diagnosed patients or those in the first year since diagnosis. (24, 25) Others (1999, 2000) have focused on patients who did not respond to or relapsed after initial treatment using interferon alfa. (26, 27) Finally, some have focused on patients transplanted in the late chronic phase (2000) (28) or after transformation to accelerated phase or blast crisis (1999). (29) Although some patients achieved complete or partial molecular remission and long-term disease-free survival, these studies do not permit conclusions free from the influence of selection bias. All auto-transplanted patients included in these reports were treated before imatinib mesylate, or newer TKIs became available.

Section Summary: Autologous HSCT

No controlled studies have evaluated autologous HSCT for treatment of CML. The available data consists of case reports and case series. In the largest series (n=200 patients), median survival was 36 months for patients transplanted during an accelerated phase and median survival data were not available for patients transplanted in chronic phase. Controlled studies are needed to permit conclusions about the impact of autologous HSCT on health outcomes in patients with CML.

Ongoing and Unpublished Clinical Trials: Autologous and Allogeneic HSCT for CML

Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials


Trial Name

Planned Enrollment

Completion Date



Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Failing TKIs Therapy


Jun 2018


Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients with Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment with Imatinib Mesylate, Desatinib, or Nilotinib


Oct 2018


Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT


Sep 2020

Table Key:

NCT: National Clinical Trial.

Practice Guidelines and Position Statements: Autologous and Allogeneic HSCT for CML

National Comprehensive Cancer Network (NCCN) Guidelines

The NCCN guidelines (v.4.2018) recommend allogeneic HSCT as an alternative treatment only for high-risk settings or in patients with advanced phase CML (30) Relevant recommendations are:

“Allogeneic HCT is no longer recommended as a first-line treatment option for CP [chronic phase] CML.”

“Allogeneic HCT is an appropriate first-line treatment option for the very rare patients presenting with blast phase at diagnosis, patients with T315I and other BCR-ABL1 mutations that are resistant to all TKIs [tyrosine kinase inhibitors], and for the rare patients intolerant to all TKIs.”

“Evaluation for allogeneic HCT….is recommended for all patients with AP [accelerated phase] CML or BP [blast phase] CML”

NCCN guidelines state: “Nonmyeloablative allogeneic HCT is a well-tolerated treatment option for patients with a matched donor and the selection of patients is based on their age and the presence of comorbidities.”

Autologous bone marrow transplant for CML is not addressed in the NCCN guidelines.

American Society for Blood and Marrow Transplantation (ASBMT)

In 2015, guidelines by the ASBMT addressed indications for autologous and allogeneic HSCT for CML. (31) Recommendations are listed in Table 2.

Table 2. Recommendations on Allogeneic and Autologous HSCT for CML


Allogeneic HSCT

Autologous HSCT


Chronic phase



Accelerated phase C N



Blast phase




Chronic phase, tyrosine kinase inhibitor intolerant



Chronic phase, tyrosine kinase inhibitor refractory



Chronic phase 2+



Accelerated phase C N



Blast phase



Table Key:

HSCT: hematopoietic stem-cell transplantation;

CML: chronic myeloid leukemia;

C: standard of care, clinical evidence available;

N: not generally recommended;

S: standard of care.

European Leukemia Net Guidelines

In 2013, European Leukemia Net issued updated guidelines for the management of CML. (32) These guidelines recommend the use of allogeneic HSCT in the following situations:

For chronic phase treatment:

o Consider HSCT as second-line therapy after failure of nilotinib or dasatinib as first-line therapy.

o Recommend HSCT in all eligible patients as third-line therapy after failure of or intolerance to 2 TKIs.

o Consider HSCT at any point if T315I mutation.

For accelerated or blast phase in newly diagnosed, TKI-naive patients:

o Begin imatinib or dasatinib.

o Recommend HSCT for all blast phase patients and for accelerated phase patients who do not achieve an optimal response.

For accelerated or blast phase as progression from chronic phase in TKI-pretreated patients:

o Recommend HSCT for all patients (after initiation of 1 of the TKIs that was not previously used or ponatinib in the case of T315I mutations).

Summary of Evidence: Autologous and Allogeneic Hematopoietic Stem-Cell Transplantation (HSCT) for Chronic Myeloid Leukemia (CML)

For individuals who have CML who receive allogeneic HSCT, the evidence includes systematic reviews, randomized controlled trials, and multiple prospective and retrospective series. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. The introduction of tyrosine kinase inhibitors (TKIs) has significantly changed the clinical use of HSCT for CML. TKIs have replaced HSCT as initial therapy for patients with chronic phase CML. However, a significant proportion of cases fail to respond to TKIs, develops resistance to them, or cannot tolerate TKIs and proceed to allogeneic HSCT. Also, allogeneic HSCT represents the only potentially curative option for those patients in the accelerated or blast phase CML. Currently, available evidence has suggested that TKI pretreatment does not lead to worse outcomes if HSCT is needed. Myeloablative conditioning regimens before HSCT are used in younger (<60 years) patients without significant comorbidities. However, for patients with more comorbidities and/or more advanced age for whom myeloablative conditioning regimens would be prohibitively high-risk, evidence has suggested that reasonable outcomes can be obtained after HSCT. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have CML who receive autologous HSCT, the evidence includes case series. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. In the largest series (n=200 patients), median survival was 36 months for patients transplanted during an accelerated phase; median survival data were not available for patients transplanted in chronic phase. Controlled studies are needed to permit conclusions on the impact of autologous HSCT on health outcomes in patients with CML. The evidence is insufficient to determine the effects of the technology on health outcomes.


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Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

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The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38222, 38230, 38232, 38240, 38241, 38242, 38243, 81265, 81266, 81267, 81268, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86828, 86829, 86830, 86831, 86832, 86833, 86834, 86835, 86849, 86950, 86985, 88240, 88241


S2140, S2142, S2150

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual

Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <>.


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25. 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 myeloyd leukemia. Haematologica. Jun 2001; 86(6):596-601. PMID 11418368

26. 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. Aug 1999; 24(3):259-64. PMID 10455363

27. 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. Dec 2000; 26(11):1165-72. PMID 11149726

28. Michallet M, Thiebaut A, Philip I, et al. Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-alpha. Leukemia. Dec 2000; 14(12):2064-9. PMID 11187894

29. Pigneux A, Faberes C, Boiron JM, et al. Autologous stem cell transplantation in chronic myeloid leukemia: a single center experience. Bone Marrow Transplant. Aug 1999; 24(3):265-70. PMID 10455364

30. NCCN – Chronic Myelogenous Leukemia. NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. Version 4.2018. Available at <> (accessed on 2018 June 15).

31. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. Nov 2015; 21(11):1863-9. PMID 26256941

32. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European Leukemia. J Clin Oncol. Aug 8 2009; 27(35):6041-51. PMID 23803709

33. Hematopoietic Stem-Cell Transplantation for Chronic Myelogenous Leukemia. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2018 February) Therapy: 8.01.30.

Policy History:

Date Reason
7/15/2018 Document updated with literature review. Coverage unchanged. References 12 and 31 added. Several references removed.
6/1/2017 Reviewed. No changes.
7/15/2016 Document updated with literature review. Coverage unchanged.
7/15/2015 Document updated with literature review. Coverage unchanged. Title changed from Stem-Cell Transplant for Chronic Myelogenous Leukemia (CML).
6/1/2014 Document updated with literature review. The following was changed: 1) Expanded coverage as follows donor leukocyte infusion (DLI) and hematopoietic progenitor cell (HPC) boost may be considered medically necessary for chronic myelogenous leukemia that has relapsed, to prevent relapse in the setting of a high-risk relapse, or to convert a patient from mixed to full chimerism; 2) DLI and HPC boost are considered experimental, investigational and/or unproven following an allogeneic stem-cell support (AlloSCS) treatment for CML that was originally considered experimental, investigational and/or unproven for the treatment of CML OR as a treatment prior to AlloSCS; 3) Short tandem repeat (STR) markers may be medically necessary when used in pre- or post-stem-cell support testing of the donor and recipient DNA profiles as a way to assess the status of donor cell engraftment following AlloSCS for CML; and 4) All other uses of STR markers are considered experimental, investigational and/or unproven if not listed in the coverage section .
4/1/2010 New medical document originating from: SUR703.017, Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Non-Malignancies; SUR703.018, Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Malignancies; SUR703.022, Cord Blood as a Source of Stem Cells (CBSC); SUR703.023, Donor Leukocyte Infusion (DLI); and SUR703.024, Tandem/Triple High-Dose Chemoradiotherapy with Stem Cell Support for Malignancies. Stem cell transplant continues to be medically necessary when stated criteria are met. NOTE: A link to the medical policies with the following titles can be found at the end of the medical policy SUR703.002, Stem-Cell Reinfusion or Transplantation Following Chemotherapy (General Donor and Recipient Information): Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Non-Malignancies; Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Malignancies; Cord Blood as a Source of Stem Cells; Donor Leukocyte Infusion (DLI); and Tandem/Triple High-Dose Chemoradiotherapy with Stem Cell Support for Malignancies.

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