Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms

POLICY NUMBER

A.8.01.21

DESCRIPTION

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) refer to a heterogeneous group of clonal hematopoietic disorders with the potential to transform into acute myelocytic leukemia. Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as a curative treatment option for patients with these disorders.

Myelodysplastic Syndromes

Myelodysplastic syndrome (MDS) can occur as a primary (idiopathic) disease or can be secondary to cytotoxic therapy, ionizing radiation, or other environmental insults. Chromosomal abnormalities are seen in 40% to 60% of patients, frequently involving deletions of chromosome 5 or 7, or an extra chromosome as in trisomy 8. Most MDS diagnoses occur in individuals older than age 55 to 60 years, with an age-adjusted incidence of 62% among individuals older than age 70 years. Patients succumb either to disease progression to acute myeloid leukemia (AML) or to complications of pancytopenias. Patients with higher blast counts or complex cytogenetic abnormalities have a greater likelihood of progressing to AML than do other patients.

Myelodysplastic Syndrome Classification and Prognosis

The French-American-British system was previously used to classify MDS into five subtypes:

1. refractory anemia;

2. refractory anemia with ringed sideroblasts;

3. refractory anemia with excess blasts;

4. refractory anemia with excess blasts in transformation;

5. chronic myelomonocytic leukemia.

The French-American-British system was supplanted by that of the World Health Organization (WHO), which differentiates between MDS defined by genetic abnormalities or by morphologic features (in the form of dysplastic cell lineages), and reduces the threshold maximum blast percentage for the diagnosis of MDS from 30% to 20%.

The most commonly used prognostic scoring system for MDS is the International Prognostic Scoring System (IPSS), which groups patients into one of four prognostic categories based on the number of cytopenias, cytogenetic profile, and the percentage of blasts in the bone marrow. This system underweights the clinical importance of severe, life-threatening neutropenia and thrombocytopenia in therapeutic decisions and does not account for the rate of change in critical parameters (eg, peripheral blood counts, blast percentage). However, the IPSS has been useful in a comparative analysis of clinical trial results and its utility confirmed at many institutions. An updated 5-category IPSS has been proposed for prognosis in patients with primary MDS or secondary AML to account for chromosomal abnormalities frequently seen in MDS. This system stratifies patients into 5 categories: very poor, poor, intermediate, good, and very good. There has been an investigation into using the 5-category IPSS to better characterize risk in MDS. A second prognostic scoring system incorporates the WHO subgroup classification that accounts for blast percentage, cytogenetics, and severity of cytopenias as assessed by transfusion requirements. The WHO Classification-based Prognostic Scoring System uses a 6-category system, which allows more precise prognostication of overall survival (OS) duration, as well as risk for progression to AML.

Myelodysplastic Syndrome Treatment

Treatment of nonprogressing MDS has involved best supportive care, including red blood cell and platelet transfusions and antibiotics. Active therapy was given only when MDS progressed to AML or resembled AML with severe cytopenias. An array of therapies are now available to treat MDS, including hematopoietic growth factors (e.g., erythropoietin, darbepoetin, granulocyte colony-stimulating factor), transcriptional-modifying therapy (e.g., U.S. Food and Drug Administration approved hypomethylating agents, nonapproved histone deacetylase inhibitors), immunomodulators (e.g., lenalidomide, thalidomide, antithymocyte globuliln, cyclosporine A), low-dose chemotherapy (e.g., cytarabine), and allogeneic hematopoietic cell transplantation (allo-HCT). Given the spectrum of treatments available, the goal of therapy must be decided upfront, whether it is to improve anemia, thrombocytopenia, or neutropenia, to eliminate the need for red blood cell transfusion, to achieve complete remission, or to cure the disease.

Allo-HCT is the only approach with curative potential, but its use is governed by patient age, performance status, medical comorbidities, the patient’s preference, risk category, and severity of MDS at presentation.

Chronic Myeloproliferative Neoplasms

Chronic myeloproliferative neoplasms are clonal bone marrow stem cell disorders. As a group, approximately 8,400 myeloproliferative neoplasms are diagnosed annually in the United States. Like MDS, myeloproliferative neoplasms primarily occur in older individuals, with approximately 67% reported in patients aged 60 years and older.

Myeloproliferative neoplasms are characterized by the slow but progressive expansion of a clone of cells with the potential evolution into a blast crisis similar to AML. Myeloproliferative neoplasms share a common stem cell-derived clonal heritage, with phenotypic diversity attributed to abnormal variations in signal transduction as the result of a spectrum of variants that affects protein tyrosine kinases or related molecules. The unifying characteristic common to all myeloproliferative neoplasms is effective clonal myeloproliferation resulting in peripheral granulocytosis, thrombocytosis, or erythrocytosis that is devoid of dyserythropoiesis, granulocytic dysplasia, or monocytosis.

Myeloproliferative Neoplasm Classification

Myeloproliferative neoplasms are a subdivision of myeloid neoplasms that includes four classic disorders: chronic myeloid leukemia, polycythemia vera, essential thrombocytopenia, and primary myelofibrosis. The WHO classification also includes chronic neutrophilic leukemia, chronic eosinophilic leukemia not otherwise specified, and myeloproliferative neoplasm unclassifiable. In the 2016 classification, mastocytosis is no longer considered a subgroup of the myeloproliferative neoplasms due to its unique clinical and pathologic features.

Myeloproliferative Neoplasm Treatment

In indolent, nonprogressing cases, therapeutic approaches are based on relief of symptoms. Supportive therapy may include prevention of thromboembolic events. Hydroxyurea may be used in cases of high-risk essential thrombocytosis and polycythemia vera, and intermediate- and high-risk primary myelofibrosis.

In 2011, the FDA approved the orally administered selective Janus kinase 1 and 2 inhibitor ruxolitinib for the treatment of intermediate- or high-risk myelofibrosis. Ruxolitinib has been associated with improved OS, spleen size, and symptoms of myelofibrosis when compared with placebo. The Randomized Study of Ruxolitinib Tablets Compared to Best Available Therapy in Subjects With Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis (COMFORT-II trial [2013]) compared ruxolitinib with best available therapy in patients who had intermediate- and high-risk myelofibrosis, and demonstrated improvements in spleen volume and OS. In a randomized trial comparing ruxolitinib with best available therapy (including antineoplastic agents, most commonly hydroxyurea, glucocorticoids) with no therapy for treatment of myelofibrosis, Harrison and colleagues reported improvements in spleen size and quality of life, but not OS. In 2019, the FDA also approved fedratinib (Inrebic®) for adults with intermediate-2 or high-risk primary or secondary myelofibrosis based on results from a double-blind, randomized, placebo-controlled trial that found improvement in spleen volume and myelofibrosis-related symptoms.

Myeloablative allo-HCT has been considered the only potentially curative therapy, but because most patients are of advanced age with attendant comorbidities, its use is limited to those who can tolerate the often-severe treatment-related adverse events of this procedure. However, the use of reduced-intensity conditioning for allo-HCT has extended the potential benefits of this procedure to selected individuals with these disorders.

Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) is a procedure in which hematopoietic stem cells are intravenously infused to restore bone marrow and immune function in cancer patients 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. Cord blood transplantation is discussed in detail in the Placental and Umbilical Cord Blood as a Source of Stem Cells policy.

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HCT. In allogeneic stem cell transplantation, 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 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.

Reduced-Intensity Conditioning for 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 definition of reduced-intensity conditioning 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 reduced-intensity conditioning 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 reduced-intensity conditioning with allo-HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism. For this policy, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative.

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

POLICY

No benefits will be provided for a covered transplant procedure or a transplant evaluation unless the Member receives prior authorization through Case Management from Blue Cross & Blue Shield of Mississippi.

Myeloablative allogeneic HCT may be considered medically necessary as a treatment of:

• myelodysplastic syndromes (see Policy Guidelines) or

• myeloproliferative neoplasms (see Policy Guidelines).

Reduced-intensity conditioning allogeneic HCT may be considered medically necessary as a risk-adapted treatment of:

• myelodysplastic syndromes or

• myeloproliferative neoplasms

in individuals who are at high-risk of intolerance of a myeloablative conditioning regimen. (See Policy Guidelines)

Myeloablative allogeneic HCT or reduced-intensity conditioning allogeneic HCT for myelodysplastic syndromes and myeloproliferative neoplasms that do not meet the criteria in the Policy Guidelines section is considered investigational.

POLICY EXCEPTIONS

For Federal Employee Program (FEP) subscribers, the Service Benefit Plan includes specific conditions in which autologous or allogeneic blood or marrow stem cell transplants would be considered eligible for coverage. 

For State and School Employee subscribers, all bone marrow/stem cell transplants must be certified as medically necessary by the Plan’s Utilization Review Vendor. No benefits will be provided for any transplant procedure unless prior approval for the transplant is obtained.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Myeloid Neoplasms

Myeloid neoplasms are categorized according to criteria developed by the World Health Organization (WHO). Neoplasms are risk-stratified using the International Prognostic Scoring System (IPSS).

2022 WHO Classification Scheme for Myeloid Neoplasm and Histiocytic/Dendritic Neoplasms

Clonal hematopoiesis (CH)

• CH of indeterminate potential (CHIP)

• Clonal cytopenia of undetermined significance (CCUS)

Myeloproliferative neoplasms (MPN)

• Chronic myeloid leukemia (CML), BCR-ABL1⁺

• Chronic neutrophilic leukemia (CNL)

• Polycythemia vera

• Primary myelofibrosis (PMF)

• Essential thrombocythemia

• Chronic eosinophilic leukemia

• MPN, not otherwise specified

• Juvenile myelomonocytic leukemia

Mastocytosis

• Cutaneous mastocytosis

• Systemic mastocytosis

• Mast cell sarcoma

Childhood MDS

• Childhood MDS with low blasts

  • Hypocellular

  • Not otherwise specified

• Childhood MDS with increased blasts

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK)

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

• Chronic myelomonocytic leukemia (CMML)

• MDS/MPN with neutrophilia

• MDS/MPN with SF3B1 mutation and thrombocytosis

• MDS/MPN, not otherwise specified

Myelodysplastic neoplasms (MDS)

• MDS with defining genetic abnormalities

  • MDS with low blasts and isolated 5q deletion (MDS-5q)

  • MDS with low blasts and SF3B1 mutation (MDS-SF3B1), or MDS with low blasts and ring sideroblasts

  • MDS with biallelic TP53 inactivation (MDS-biTP53)

• MDS, morphologically defined

  • MDS with low blasts (MDS-LB)

  • MDS, hypoplastic (MDS-h)

  • MDS with increased blasts (MDS-IB)

    • MDS-IB1

    • MDS-IB2

    • MDS with fibrosis (MDS-f)

Acute myeloid leukemia (AML)

• AML with defining genetic abnormalities

• AML, defined by differentiation

Secondary myeloid neoplasms

• Myeloid neoplasms post cytotoxic therapy

• Myeloid neoplasms associated with germline predisposition

Dendritic cell and histiocytic neoplasms

• Plasmacytoid dendritic cell neoplasms

• Langerhans cell and other dendritic cell neoplasms

• Histiocytic neoplasms

Acute leukemias of ambiguous lineage (ALAL)

• ALAL with defining genetic abnormalities

• ALAL, immunophenotypically defined

Genetic tumor syndromes with predisposition to myeloid neoplasia

Risk Stratification of Myelodysplastic Syndromes

Risk stratification for MDS is performed using the IPSS (see Table 1). This system was developed after pooling data from 7 studies that used independent, risk-based prognostic factors. The prognostic model and the scoring system were based on blast count, degree of cytopenia, and blast percentage. Risk scores were weighted relative to their statistical power. This system is widely used to group individuals into either low-risk or high-risk groups (see Table 2). The low-risk group includes low-risk and Intermediate-1 IPSS groups; treatment goals in low-risk MDS individuals are to improve quality of life and achieve transfusion independence. In the high-risk group, which includes intermediate-2 and high-risk IPSS groups, treatment goals are slowing disease progression to AML and improving survival. The IPSS is usually calculated on diagnosis. The role of lactate dehydrogenase, marrow fibrosis, and beta 2-microglobulin also should be considered after establishing IPSS. If elevated, the prognostic category worsens by one category change.

Table 1. International Prognostic Scoring System: Myelodysplastic Syndrome Prognostic Variables

NA: not applicable 

Table 2. International Prognostic Scoring System: Myelodysplastic Syndrome Clinical Outcomes

 An updated 5-category IPSS has been proposed for prognosis in individuals with primary MDS or secondary AML to account for chromosomal abnormalities frequently seen in MDS. This system stratifies patients into 5 categories: very poor, poor, intermediate, good, and very good. There has also been an investigation into using the 5-category IPSS to better characterize risk in MDS.

Given the long natural history of myelodysplastic syndrome, allogeneic HCT is typically considered in individuals with increasing numbers of blasts, signaling a possible transformation to acute myeloid leukemia. Subtypes falling into this category include refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or chronic myelomonocytic leukemia.

Individuals with refractory anemia with or without ringed sideroblasts may be considered candidates for allo-HCT when chromosomal abnormalities are present, or when the disorder is associated with the development of significant cytopenias (e.g., neutrophils <500/mm³, platelets <20,000/mm³).

Individuals with MPNs may be considered candidates for allo-HCT when there is a progression to myelofibrosis or toward acute leukemia. In addition, allo-HCT may be considered in individuals with essential thrombocythemia with an associated thrombotic or hemorrhagic disorder. The use of allo-HCT should be based on the following criteria: cytopenias, transfusion dependence, increasing blast percentage over 5%, and age.

Some individuals for whom a conventional myeloablative allo-HCT could be curative may be candidates for reduced-intensity conditioning allo-HCT. These include individuals whose age (typically older than 60 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status) preclude the use of a standard myeloablative conditioning regimen. The ideal allogeneic donors are human leukocyte antigen (HLA)-identical siblings, matched at the HLA-A, -B, and -DR loci (6/6). Related donors mismatched at one locus are also considered suitable donors. A matched, unrelated donor identified through the National Marrow Donor Registry is typically the next option considered. Recently, there has been interest in haploidentical donors, typically a parent or a child of the individual, who usually share only 3 of the 6 major histocompatibility antigens. Most individuals will have such a donor; however, the risk of graft-versus-host disease and overall morbidity of the procedure may be severe, and experience with these donors is not as graft-versus-host disease extensive as that with matched donors.

Evidence and clinical guidelines suggest reduced-intensity conditioning allo-HCT may be considered as a risk-adapted strategy for high-risk individuals of myeloablative conditioning-intolerance as follows:

MDS

• Older age

• IPSS intermediate-2 or high risk

• Multiple comorbidities (e.g., HCT-comorbidity index (HCT-CI) score higher than 2)

• Red blood cell transfusion dependence

• Neutropenia

• Thrombocytopenia

• High-risk cytogenetics

• Increasing blast percentage

MPN

• Cytopenias

• Transfusion dependence

• Increasing blast percentage over 5%

• Age 60 to 65 years

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

3/25/2004: See policy "High-Dose Chemotherapy with Hematopoietic Stem Cell Support for Malignancies" prior to 3/25/2004, separate policy developed and aligned with BCBSA policy # 8.01.21 per approval by Medical Policy Advisory Committee (MPAC).

8/19/2004: Code Reference section completed.

11/18/2004: Reviewed by MPAC, no changes.

10/19/2005: Code Reference section updated, codes 38204, 38205, 38207-38215, 38242, G0355-G0364 added. J9000-J9999 deleted; ICD9 procedure codes 41.02, 41.03, 41.08 added. Description of ICD9 procedure code 99.25 revised.  HCPCS statement added for J9000-J9999 codes.

03/10/2006: Coding updated. CPT4/HCPCS 2006 revisions added to policy.

09/12/2006: Coding updated. ICD9 2006 revisions added to policy.

5/18/2007: Policy reviewed, description updated. Myeloablative or nonmyeloablative added to policy statement as medically necessary as a treatment of myelodysplastic syndrome.

12/20/2007: Coding updated per 2008 CPT/HCPCS revisions.

5/21/2008: Policy reviewed, no changes.

7/14/2008: Policy updated. High dose chemotherapy terminology replaced with allogeneic SCT. Policy statements intent remain unchanged. "Myeloproliferative" diseases added to policy title "High Dose Chemotherapy" removed from title.

8/7/2009: Policy Description Section updated to include specific definitions and descriptions for Conventional Preparative Conditioning for HSCT, Reduced-Intensity Conditioning for Allogeneic HSCT, Myelodysplastic Syndromes, and Chronic Myeloproliferative Neoplasms, Policy Statement Section updated to add Reduced -intensity conditioning allogeneic HSCT as medically necessary for the treatment of myelodysplastic syndromes or myeloproliferative neoplasms, Policy Guidelines Section updated with 2008 WHO information for Myeloid Neoplasms, risk stratification information, clinical suggestions for RIC allogeneic HSCT, Updated Coding Section with CPT-4 code 38230 added to Covered Table, Removed deleted ICD-9 diagnosis code 238.7 from Covered Table, Removed deleted HCPCS codes G0265, G0266, G0267, and G0363 from Covered Table.

6/04/2010: Title changed from "Allogeneic Stem-Cell Transplantation for Myelodysplastic and Myeloproliferative Diseases" to "Allogeneic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms." FEP and State and School Employee verbiage added to Policy Exceptions section. New CPT codes 86825 and 86826 added to covered table.

12/28/2010: Policy reviewed; no changes.

01/17/2012: Policy reviewed; no changes.

03/13/2013: Policy reviewed; no changes.

03/11/2014: Policy reviewed; no changes.

12/19/2014: Policy title changed from "Allogeneic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms" to "Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms." Policy description updated regarding MPN Treatment. Added "Myeloablative" to the first medically necessary policy statement. Added the following investigational statement: Myeloablative allogeneic HSCT or reduced-intensity conditioning allogeneic HSCT for myelodysplastic syndromes and myeloproliferative neoplasms that does not meet the criteria in the Policy Guidelines section is considered investigational.

08/21/2015: Code Reference section update to add ICD-10 codes. Revised the descriptions for CPT codes 38240 and 38242; removed deleted code CPT 96445 and replaced with CPT code 96446.

04/04/2016: Policy description updated regarding myelodysplastic syndromes, myeloproliferative neoplasms, and FDA regulations. Policy statements unchanged. Policy guidelines updated regarding risk stratification of MDS and to add medically necessary and investigative definitions.

05/25/2016: Policy number A.8.01.21 added.

09/30/2016: Code Reference section updated to add new ICD-10 diagnosis code D47.Z2.

01/31/2017: Policy updated to change "hematopoietic stem-cell transplantation" to "hematopoietic cell transplantation." Policy description updated regarding the 5-category IPSS. Policy statements unchanged.

12/21/2017: Code Reference section updated to add new 2018 CPT code 38222. Revised descriptions for CPT codes 38220 and 38221 effective 01/01/2018. Removed deleted ICD-10 procedure codes 30230G1, 30233G1, 30240G1, 30243G1, 30230Y1, 30233Y1, 30240Y1, 30243Y1 and ICD-9 procedure codes 41.02, 41.03, 41.05, and 41.08.

02/12/2018: In policy title, "Hematopoietic Stem-Cell Transplantation" changed to "Hematopoietic Cell Transplantation." Policy description updated. Policy statements unchanged. Policy Guidelines updated regarding risk stratification of MDS.

03/11/2019: Policy reviewed. Policy statements unchanged. Code Reference section updated to remove deleted CPT code 86822 and HCPCS code G0364.

02/20/2020: Policy description updated regarding hematopoietic cell transplantation and conventional conditioning. Policy statement regarding reduced-intensity conditioning allo-HCT updated to specify it as a risk-adapted strategy for patients at high-risk of MAC intolerance. Policy Guidelines updated regarding reduced-intensity conditioning allo-HCT as a risk-adapted strategy for high-risk patients of MAC-intolerance.

03/05/2021: Policy description updated. Policy statements unchanged. Table regarding risk stratification of MDS updated in Policy Guidelines.

01/03/2022: Code Reference section updated to make note of deleted ICD-10 procedure code.

02/17/2022: Policy description updated regarding myeloproliferative neoplasm classification and myeloproliferative neoplasm treatment. Policy statements unchanged. Policy Guidelines updated regarding the 2016 WHO Classification Scheme for Myeloid Neoplasm and Acute Leukemia.

09/30/2022: Code Reference section updated to revise the description for ICD-10 diagnosis code C94.6, effective 10/01/2022.

02/23/2023: Policy description updated regarding myelodysplastic syndrome classification and prognosis and allo-HCT. Policy statement updated to change "patients" to "individuals." Policy Guidelines updated regarding the 2022 WHO classification scheme for myeloid neoplasm and histiocytic/dendritic neoplasms.

12/21/2023: Code Reference section updated to revise the code description for CPT code 96446, effective 01/01/2024.

02/23/2024: Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "patients" to "individuals."

04/04/2025: Policy description updated. Policy statements unchanged.

SOURCE(S)

Blue Cross Blue Shield Association Policy # 8.01.21

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy. 

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.