212 Form

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Medical Policy Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia Table of Contents • Policy: Commercial • Description • Information Pertaining to All Policies
• Authorization Information • Policy History • References
• Coding Information

Policy Number: 212 BCBSA Reference Number: 8.01.30 (For Plan internal use only) Related Policies
• Hematopoietic Cell Transplantation for Non-Hodgkin Lymphomas, #143 • Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms, #155 • Hematopoietic Cell Transplantation for Acute Myeloid Leukemia, #150 Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity

Allogeneic hematopoietic cell transplantation (HCT) using a myeloablative conditioning regimen may be considered MEDICALLY NECESSARY as a treatment of chronic myeloid leukemia.

Allogeneic HCT using a reduced-intensity conditioning regimen may be considered MEDICALLY NECESSARY as a treatment of chronic myeloid leukemia in individuals who meet clinical criteria for an allogeneic HCT but who are not considered candidates for a myeloablative conditioning allogeneic HCT.

Note: Some individuals for whom a conventional myeloablative allotransplant could be curative may be considered candidates for reduced-intensity conditioning allogeneic hematopoietic cell transplantation (HCT). They include those individuals whose age (typically >60 years) or comorbidities (eg, liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score) preclude use of a standard myeloablative conditioning regimen.

Autologous HCT is INVESTIGATIONAL as a treatment of chronic myeloid leukemia.

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Prior Authorization Information
Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.

Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

Outpatient Commercial Managed Care (HMO and POS) Prior authorization is required. Commercial PPO and Indemnity Prior authorization is required.

Requesting Prior Authorization Using Authorization Manager Providers will need to use Authorization Manager to submit initial authorization requests for services. Authorization Manager, available 24/7, is the quickest way to review authorization requirements, request authorizations, submit clinical documentation, check existing case status, and view/print the decision letter. For commercial members, the requests must meet medical policy guidelines.
To ensure the service request is processed accurately and quickly: • Enter the facility’s NPI or provider ID for where services are being performed. • Enter the appropriate surgeon’s NPI or provider ID as the servicing provider, not the billing group.

Authorization Manager Resources Refer to our Authorization Manager page for tips, guides, and video demonstrations. CPT Codes / HCPCS Codes / ICD Codes Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

The following codes are included below for informational purposes only; this is not an all-inclusive list.

The above medical necessity criteria MUST be met for the following codes to be covered for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity:

CPT Codes CPT codes:

Code Description 38240 Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor

HCPCS Codes HCPCS codes: Code Description S2142 Cord blood derived stem-cell transplantation, allogeneic S2150 Bone marrow or blood-derived peripheral stem-cell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical surgical, diagnostic and emergency services)

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Description Chronic Myeloid Leukemia Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the presence of a chromosomal abnormality called the Philadelphia chromosome, which results from a reciprocal translocation between the long arms of chromosomes 9 and 22. This cytogenetic change results in constitutive activation of the fusion gene BCR-ABL, a tyrosine kinase 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. The disease accounts for about 15% of newly diagnosed cases of leukemia in adults and occurs in 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 secondary to anemia and splenomegaly. A diagnosis is based on the presence of the Philadelphia chromosome abnormality by routine cytogenetics, or by detection of abnormal BCR-ABL products by fluorescence in situ hybridization 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.

Treatment Historically, the only curative therapy for CML in blast phase has been allogeneic hematopoietic cell transplantation (allo-HCT), 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 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 variants that cause resistance to the drug. Even so, the overall survival of patients who present in the chronic phase is greater than 95% at 2 years and 80% to 90% at 5 years.2,

For CML, 2 other tyrosine kinase inhibitors ([TKIs]; dasatinib, nilotinib) have received marketing approval from the U.S. Food and Drug Administration (FDA) as first-line therapies or following failure or patient intolerance of imatinib. Three additional TKIs (bosutinib, ponatinib, asciminib) 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 allo-HCT. Detection of BCR-ABL variants may be important in determining an alternative TKI; the presence of the T315I variant is associated with resistance to all TKIs and should indicate the need for allo-HCT or experimental therapy. Tyrosine kinase inhibitors have been associated with long-term remissions; however, if disease progression occurs on TKI therapy, allo-HCT is generally indicated and offers the potential for cure.

Hematopoietic Cell Transplantation Hematopoietic cell transplantation is a procedure in which hematopoietic stem cells are intravenously infused to restore bone marrow and immune function in patients with cancer who receive bone marrow- toxic doses of cytotoxic drugs with or without whole-body radiotherapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or a donor (allo-HCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates.

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Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HCT. In allo-HCT, immunologic compatibility between donor and patient is a critical factor for achieving a successful outcome. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. Human leukocyte antigen refers to the gene complex expressed at the HLA-A, -B, and -DR (antigen-D related) loci on each arm of chromosome 6. An acceptable donor will match the patient at all or most of the HLA loci.

Conditioning for Hematopoietic Cell Transplantation

Conventional Conditioning The conventional (“classical”) practice of allo-HCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to cause bone marrow ablation in the recipient. The beneficial treatment effect of this procedure is due to a combination of the initial eradication of malignant cells and subsequent graft-versus-malignancy effect mediated by non-self-immunologic effector cells. While the slower graft-versus-malignancy effect is considered the potentially curative component, it may be overwhelmed by existing disease in the absence of pretransplant conditioning. Intense conditioning regimens are limited to patients who are sufficiently medically fit to tolerate substantial adverse effects. These include opportunistic infections secondary to loss of endogenous bone marrow function and organ damage or failure caused by cytotoxic drugs. Subsequent to graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and graft-versus-host disease, which increases susceptibility to opportunistic infections.

The success of autologous HCT is predicated on the potential of cytotoxic chemotherapy, with or without radiotherapy, to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of the bone marrow with presumably normal hematopoietic stem cells obtained from the patient before undergoing bone marrow ablation. Therefore, autologous HCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HCT are also susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not graft-versus-host disease (GVHD).

Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses of cytotoxic drugs or less intense regimens of radiotherapy than are used in traditional full-dose myeloablative conditioning treatments. Although the clinical definition of RIC is variable with numerous versions employed, all regimens seek to balance the competing effects of relapse due to residual disease and non-relapse mortality. The goal of RIC is to reduce disease burden and to minimize associated treatment-related morbidity and non-relapse mortality in the period during which the beneficial graft-versus-malignancy effect of allogeneic transplantation develops. Reduced-intensity conditioning regimens range from nearly total myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allo-HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism. In this review, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative.

Summary Description Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the presence of a chromosomal abnormality called the Philadelphia chromosome, which results from a reciprocal translocation between the long arms of chromosomes 9 and 22. Chronic myeloid leukemia most often presents in a chronic phase from which it progresses to an accelerated and then a blast phase. Allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment option for CML.

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

Policy History Date Action 3/2026 Annual policy review. Policy updated with literature review through November 14, 2025; no references added. Policy statements unchanged. 3/2025 Annual policy review. References updated. Policy statements unchanged. 3/2024 Annual policy review. Description, summary, and references updated. Policy statement unchanged. 9/2023 Policy clarified to include prior authorization requests using Authorization Manager.
3/2023 Annual policy review. Minor editorial refinements to policy statements; intent unchanged. 1/2023 Medicare information removed. See MP #132 Medicare Advantage Management for local coverage determination and national coverage determination reference.
2/2022 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 3/2021 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 10/2020 Clarified coding information. 4/2020 Bone marrow harvesting codes were removed. Outpatient prior authorization is not required.
3/2020 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 3/2019 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 1/2019 Outpatient prior authorization is required for all commercial products including Medicare Advantage. Effective 1/1/2019. 3/2018 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 2/2018 Clarified coding information. 3/2017 Annual policy review. Title changed. Myelogenous changed to myeloid. New references added. 3/1/2017

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3/2016 Annual policy review. New references added. 9/2015 Clarified coding information. 6/2014 Updated Coding section with ICD10 procedure and diagnosis codes, effective 10/2015. 3/2014 Annual policy review. New references added. 11/2011- 4/2012 Medical policy ICD 10 remediation: Formatting, editing and coding updates. No changes to policy statements.
7/2011 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 9/2010 Reviewed - Medical Policy Group - Hematology and Oncology. No changes to policy statements. 8/1/2010 New policy, effective 8/1/2010, describing covered and non-covered indications. Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines

References

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