Latest Review Date: January 2024

Category: Surgery                                                    

POLICY:

Myeloablative allogeneic HCT (allo-HCT) may be considered medically necessary as a treatment of:

• Myelodysplastic syndromes (see Policy Guidelines); OR
• Myeloproliferative neoplasms (see Policy Guidelines).

In individuals who are at high-risk of intolerance of a myeloablative conditioning regimen, reduced-intensity conditioning (RIC) allo-HCT may be considered medically necessary as a risk-adapted treatment of

• Myelodysplastic syndromes (see Policy Guidelines); OR
• Myeloproliferative neoplasms (see Policy Guidelines).

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

For individuals with Systemic Mastocytosis (SM):

• Allogeneic HCT, myeloablative or reduced-intensity conditioning, may be considered medically necessary:
  • As salvage therapy for patients with advanced SM (e.g., Aggressive systemic mastocytosis (ASM), Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), or Mast cell leukemia) that does not respond adequately to initial medical therapy.
  • For SM patients with an associated hematologic neoplasm (AHN) or mast cell leukemia (MCL)-AHN, in which the SM component manifests a significant response, but the AHN continues to progress characterized by the worsening of clinically significant cytopenias and/or elevated blood counts with dysplasia, monocytosis, eosinophilia, and/or increased peripheral blood and/or bone marrow blasts.
  • High-risk molecular and/or karyotypic features (e.g., monosomy 7, complex karyotype) and/or one or more high-risk non-KIT mutations (e.g., SRSF2, ASXL1, and/or RUNX1)  in an individual whose best response to midostaurin is stable disease or a partial response of either the SM or AHN component.
• Allogeneic HCT is considered investigational to treat individuals with indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM).

POLICY GUIDELINES:

Myeloid Neoplasms

Myeloid neoplasms are categorized according to criteria developed by the World Health Organization (WHO). Neoplasms are risk-stratified use 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 PG1). 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 PG2). 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. IPSS is usually calculated on diagnosis. The role of lactate dehydrogenase, marrow fibrosis, and β2-microglobulin also should be considered after establishing IPSS. If elevated, the prognostic category worsens by one category change.

Table PG1. International Prognostic Scoring System: Myelodysplastic Syndrome Prognostic Variables

Variable	0	0.5	1.0	1.5	2.0
Marrow blasts, %	<5	5-10	NA	11 to 20	21 to 30
Karyotype	Good	Intermediate	Poor	NA	NA
Cytopenias	0/1	2/3	NA	NA	NA

NA:Not applicable.

Table PG2. International Prognostic Scoring System: Myelodysplastic Syndrome Clinical Outcomes

Risk Group	Total Score	Median Survival, y	Time for 25% of patients to Progress to AML
Low	0	5.7	9.4 years
Intermediate-1	0.5 to 1.0	3.5	3.3 years
Intermediate-2	1.5 to 2.0	1.2	1.12 years
High	≥2.5	0.4	0.2 years

AML: acute myelocytic leukemia

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 (see Schanz et al, 2012). This system stratifies individuals into five 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 MDS, allogeneic hematopoietic cell transplantation (allo-HCT) is typically considered in individuals with increasing numbers of blasts, signaling a possible transformation to AML. Subtypes falling into this category include refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or chronic myelomonocytic leukemia (CMML).

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 myeloproliferative neoplasms (MPN) 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. 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 >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 three of the six major histocompatibility antigens. Most individuals will have such a donor; however, the risk of graft-versus-host disease (GVHD) 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 MAC-intolerance as follows:

MDS

• Older age
• IPSS intermediate-2 or high risk
• Multiple comorbidities (e.g., hematopoietic cell transplantation-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.

DESCRIPTION OF PROCEDURE OR SERVICE:

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 HCT (allo-HCT) has been proposed as a curative treatment option for individuals with these disorders.

Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) can occur as a primary (idiopathic) disease, or be secondary to cytotoxic therapy, ionizing radiation, or other environmental insult. Chromosomal abnormalities are seen in 40% to 60% of individuals, 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 of 55 to 60 years, with an age-adjusted incidence of about 62% among individuals over age 70 years. Individuals succumb either to disease progression to acute myeloid leukemia  (AML) or to complications of pancytopenias. Individuals with higher blast counts or complex cytogenetic abnormalities have a greater likelihood of progressing to AML than do other individauls.

Myelodysplastic Classification and Prognosis

The French-American-British (FAB) system was 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; and, 5) chronic myelomonocytic leukemia. The French-American-British system has been supplanted by that of the World Health Organization (WHO), 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 individuals into one of four prognostic categories based on the number of cytopenias, cytogenetic profile and the percentage 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, (e.g., peripheral blood count, blast percentage). However, the IPSS has been useful in comparative analysis of clinical trial results and its utility confirmed at many institutions. 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 five categories: very poor, poor, intermediate, good, and very good. There has been 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 (WPSS) uses a 6-category system that allows more precise prognostication of overall survival duration as well as risk for progression to AML. 

Myelodysplastic Syndrome Treatment

Treatment of  non-progressing MDS has previously involved best supportive care, including red blood cell (RBC) 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 [FDA] -approved hypomethylating agents, non-approved histone deacetylase inhibitors), immunomodulators (e.g., lenalidomide, thalidomide, antithymocyte globulin, cyclosporine A), low-dose chemotherapy (e.g., cytarabine), and allogeneic 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 (CR); or to cure the disease.

Allogeneic HCT is the only approach with curative potential, but its use is governed by indivial age, performance status, medical comorbidities, the individuals preference, risk category, and severity of MDS at presentation.

Chronic Myeloproliferative Neoplasms

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

MPNs are characterized by the slow but progressive expansion of a clone of cells with the potential evolution into a blast crisis similar to AML. MPNs 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 MPNs 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 4 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, non-progressing 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.

The FDA (2011) 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 individuals 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 et al (2012) 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 allogeneic HCT has been considered the only potentially curative therapy, but because most inidividuals are of advanced age with attendant comorbidities, its use is limited to those who can tolerate the often severe treatment-related adverse effects of this procedure.  However, the use RIC for allogeneic HCT has extended the potential benefits of this procedure to selected individuals with these disorders.

Systemic Mastocytosis

In 2016, the World Health Organization (WHO) classified, mastocytosis as no longer a subgroup of the myeloproliferative neoplasms due to its unique clinical and pathologic features. Mastocytosis has been defined in medical literature as an abnormal accumulation of mast cells in one or more organ systems. The three major categories of mastocytosis are: cutaneous mastocytosis (CM), systemic mastocytosis (SM) and mast cell sarcoma. These diseases occur in both children and adults. The World Health Organization's classification system further divided systemic mastocytosis into five subtypes: indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL).

Indolent systemic mastocytosis (ISM) is used for individuals with SM without an associated hematologic neoplasm and with fewer than 20 percent mast cells in the bone marrow. It is the most prevalent form of SM in adults. Smoldering systemic mastocytosis is used for individuals who exhibit higher rates of progression to more advanced diseases, such as aggressive systemic mastocytosis. These individuals also typically have skin lesions of urticaria pigmentosa/maculopapular cutaneous mastocytosis. Aggressive systemic mastocytosis is used for individuals with SM who do not have an associated hematologic neoplasm and with fewer than 20 percent mast cells in the bone marrow. Systemic mastocytosis with an associated hematologic neoplasm is diagnosed when a individual fulfills clinical criteria for SM and another hematologic syndrome or neoplasia according to WHO criteria, most commonly myelodysplastic or myeloproliferative neoplasms or an overlap of the two diseases. 

Treatment

In indolent or smoldering cases of systemic mastocytosis, therapeutic approaches are based on relief of symptoms. These treatments include antihistamines, antileukotriene drugs, glucocorticoids, omalizumab, and cytoreductive agents. 

Myeloablative allogeneic HCT has been considered the only potentially curative therapy for advanced systemic mastocytosis. However, the use RIC of conditioning regimens for allogeneic HCT has extended the potential benefits of this procedure to selected individuals with this disorder.

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 individuals 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. The use of cord blood is discussed in Medical Policy #439: Placental/Umbilical Cord Blood as a Source of Stem Cells.

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. HLA 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.

Conventioning for Hematopoietic Cell Transplantation

Conventional Conditioning

The conventional (“classical”) practice of allogeneic 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 in this procedure is due to a combination of initial eradication of malignant cells and subsequent graft-versus-malignancy (GVM) effect mediated by  non-self-immunologic effector cells. While the slower GVM effect is considered to be the potentially curative component, it may be overwhelmed by extisting disease in the absence of pretransplant conditioning.  Intense conditioning regimens are limited to individuals who are sufficiently fit medically to tolerate substantial adverse effects. These include opportunistic infections secondary to loss of endogenous bone marrow function and organ damage or failure caused by the cytotoxic drugs. Subsequent to graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and GVHD, 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 individual before undergoing bone marrow ablation. Therefore, autologous HCT is typically performed as consolidation therapy when the individual’s disease is in complete remission. Individuals who undergo autologous HCT are also susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not GVHD

Reduced-Intensity Conditioning for Allogeneic HCT

Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses or less intense regimens of cytotoxic drugs or radiation than are used in traditional full-dose myeloablative conditioning treatments. Although the 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 (NRM) in the period during which the beneficial graft-versus-malignancy effect of allogeneic transplantation develops.  RIC regimens from nearly totally myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and individual condition. Individuals who undergo RIC with allogeneic 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.

KEY POINTS:

The most recent literature update was performed through November 13, 2023.

Summary of Evidence

For individuals who have myelodysplastic syndrome (MDS) who receive myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT), the evidence includes systemic reviews, randomized controlled trials (RCTs), and numerous case series, which are often heterogeneous in terms of diseases included. Relevant outcomes are overall survival (OS), disease-specific survival, and treatment-related mortality and morbidity. Primarily uncontrolled, observational studies of hematopoietic cell transplantation (HCT) for MDS have reported a relatively large range of overall and progression free survival (PFS) rates, which reflect the heterogeneity in individual populations, conditioning regimens, and other factors. Reported estimates for 3- to 5-year OS of 40% to 50% are typical. Evidence from randomized and nonrandomized comparisons has suggested that RIC may be used as a risk-adapted strategy in high-risk individuals who are older and with more comorbidities without significantly worsening OS. RIC appears to be associated with lower rates of nonrelapse mortality but higher cancer relapse than MAC HCT. At present, HCT is the only potentially curative treatment option for patients with MDS. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have myeloproliferative neoplasms who receive MAC or RIC allo-HCT, the evidence includes a systematic review and retrospective observational series. Relevant outcomes are OS, disease-specific survival, and treatment-related mortality and morbidity. Evidence has suggested that RIC may be used as a risk-adapted strategy in high-risk individuals who are older and have more comorbidities without significantly worsening OS. RIC appears to be associated with lower rates of nonrelapse mortality but higher cancer relapse than myeloablative HCT. At present, HCT is the only potentially curative treatment option for individuals with myeloproliferative neoplasms. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with advanced systemic mastocytosis (SM) who receive MAC or RIC allo-HCT, reports are limited with only small retrospective case series. No studies have randomly assigned individuals to allogeneic HCT versus medical therapy alone. Relevant outcomes are OS, disease-specific survival, and treatment-related mortality and morbidity. MAC or RIC allo-HCT is the only potentially curative treatment option for individuals with advanced SM. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM) who receive MAC or RIC all-HCT,  literature data is scarce. The role of allogeneic stem cell transplantation is still not defined in the treatment of these diseases. There is not enough research to show that the MAC or RIC allo-HCT improves health outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

Current National Comprehensive Cancer Network clinical guidelines for myelodysplastic syndromes (v.1.2023) make the following general recommendation about allo-HCT:

“For patients who are transplant candidates, an HLA [human leukocyte antigen]-matched sibling, or HLA-matched unrelated donor can be considered. Results with HLA-matched unrelated donors have improved to levels comparable to those obtained with HLA-matched siblings. With the increasing use of cord blood or HLA-haploidentical related donors, HCT has become a viable option for many patients. High-dose conditioning is typically used for younger patients, whereas RIC [reduced-intensity conditioning] for HCT is generally the strategy in older individuals.”

Specific National Comprehensive Cancer Network recommendations for HCT for treatment of myelodysplastic syndromes are outlined in Table 2.

Table 2. Guidelines for Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes

Prognostic Category	Recommendations for Allo-HCT
IPSS low/intermediate-1 OR IPSS-R very low, low, intermediate OR WPSS very low, low, intermediate	Consider allo-HCT for select patients who have clinically relevant thrombocytopenia or neutropenia, with disease progression or no response after azacitidine/decitabine or immunosuppressive therapy Consider allo-HCT for patients who have symptomatic anemia with no 5q deletion, with serum erythropoietin level >500 mU/mL or lower serum erythropoietin level with inadequate response to erythropoietin stimulating agents and/or lenalidomide, with poor probability of or inadequate response/intolerance to immunosuppressive therapy, and no response or intolerance to azacitidine/decitabine or immunosuppressive therapy Consider allo-HCT for patients who have symptomatic anemia with del(5q), with inadequate response/intolerance to lenalidomide and/or erythropoietin stimulating agents, and no response or intolerance to azacitidine/decitabine or immunosuppressive therapy
IPSS intermediate-2, high OR IPSS-R intermediate, high, very high OR WPSS high, very high	Recommend allo-HCT if a high-intensity therapy candidate and transplant candidate and donor stem cell source is available.

allo: allogeneic; HCT: hematopoietic cell transplantation; IPSS: International Prognostic Scoring System; WPSS: WHO Classification-based Prognostic Scoring System.

Table 3 summarizes the National Comprehensive Cancer Network recommendations (v.3.2022) on the use of allo-HCT for the treatment of myeloproliferative neoplasms. The guidelines note that selection of allo-HCT should be based on age, performance status, major comorbid conditions, psychosocial status, patient preference, and availability of caregiver.

Table 3. Guidelines for Allogeneic Hematopoietic Cell Transplantation for Myeloproliferative Neoplasms

Prognostic Category	Recommendations for Allo-HCT
Lower-risk Myelofibrosis MIPSS-70≤3 MIPSS-70+ Version 2.0 ≤3 DIPSS-Plus ≤1 DIPSS ≤2 MYSEC-PM <14	In symptomatic patients with disease progression despite treatment with ruxolitinib, peginterferon alfa-2a, and/or hydroxyurea (if cytoreduction would be symptomatically beneficial), consider allo-HCT immediately or bridging therapy to decrease marrow blasts to an acceptable level prior to transplant Evaluation for allo-HCT is recommended for patients with low platelet counts or complex cytogenetics
Higher-risk Myelofibrosis MIPSS-70 ≥4 MIPSS-70+ Version 2.0 ≥4 DIPSS-Plus >1 DIPSS >2 MYSEC-PM ≥14	Consider allo-HCT immediately or bridging therapy can be used to decrease marrow blasts to an acceptable level prior to transplant Evaluation for allo-HCT is recommended for all patients
Disease progression to advanced-stage/AML	Induce remission with hypomethylating agents ± JAK inhibitors or intensive induction chemotherapy followed by allo-HCT

allo: allogeneic; AML: acute myeloid leukemia; DIPSS: Dynamic International Prognostic Scoring System; HCT: hematopoietic cell transplantation; MIPSS: Mutation-Enhanced International Prognostic Scoring System; MYSEC-PM: Myelofibrosis Secondary to PV [polycythemia vera] and ET [essential thrombocythemia]-Prognostic Model; JAK: Janus kinase.

American Society of Transplantation and Cellular Therapy

In 2020, the American Society of Transplantation and Cellular Therapy (formerly The American Society for Blood and Marrow Transplantation) published updated guidelines on indications for HCT and immune effector cell therapy based on the recommendations of a multiple-stakeholder task force. Table 4 summarizes categorizations for allo-HCT in adults.

Table 4. Recommendations for the Use of HCT to Treat Myelodysplastic Syndromes, Myelofibrosis, and Myeloproliferative Neoplasms

Indication	Recommendation
Myelodysplastic syndromes
Low/intermediate-1 risk	Standard of care, clinical evidence available (large clinical trials are not available; however, sufficiently large cohort studies have shown efficacy with “acceptable risk of morbidity and mortality”)
Intermediate-2/high-risk	Standard of care (“well defined and generally supported by evidence in the form of high-quality clinical trials and/or observational studies”)
Myelofibrosis and myeloproliferative neoplasms
Primary, low-risk	Standard of care (“well defined and generally supported by evidence in the form of high-quality clinical trials and/or observational studies”)
Primary, intermediate/high-risk	Standard of care (“well defined and generally supported by evidence in the form of high-quality clinical trials and/or observational studies”)
Secondary	Standard of care (“well defined and generally supported by evidence in the form of high-quality clinical trials and/or observational studies”)
Hypereosinophilic syndromes, refractory	Standard of care, rare indication (clinical trials and observational studies are not feasible due to low incidence; small cohorts have shown efficacy with “acceptable risk of morbidity and mortality”)

 

In 2022, the ASTCT published practice recommendations for HCT in the management of myelodysplastic syndromes. A standardized system for grading the levels of evidence was applied (as recommended by the ASTCT Steering Committee for evidence-based reviews). Table 5 summarizes allo-HCT specific recommendations by ASTCT.

Table 5. Recommendations for  the Use of Allogeneic Hematopoietic Cell Transplantion to Treat Myelodysplastic Syndromes

Indication/Consideration	Recommendation	Grade of Recommendation
Should allogeneic HCT routinely be offered early for advanced (int-2/high) de novo MDS?	Yes	A
Should allogeneic HCT routinely be offered early for lower risk (low/int-1) de novo MDS?	No	B

HCT: hematopoietic cell transplantation; MDS: myelodysplastic syndrome.

 

U.S. Preventive Services Task Force Recommendations

Not applicable

KEY WORDS:

Allogeneic Cell Support, Bone Marrow Transplantation, Myeloablation, Myeloproliferative Disorders, Reduced-Intensity Conditioning, Myeloproliferative Syndrome, Myelodysplastic Syndrome, High-Dose Chemotherapy, Myelofibrosis, Cell Transplant, Myelodysplastic Diseases, Hematopoietic Cell Transplant (HCT), Myeloproliferative Neoplasm (MPN), Systemic Mastocytosis, Aggressive systemic mastocytosis (ASM), Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and Mast cell leukemia (MCL), Mast cell sarcoma (MCS), Acute leukemias of ambiguous lineage (ALAL), Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), Clonal hematopoiesis (CH), Clonal hematopoiesis of indeterminate potential (CHIP), Clonal cytopenia of undetermined significance (CCUS), Chronic myelomonocytic leukemia (CMML), Cutaneous mastocytosis, Chronic neutrophilic leukemia (CNL), Polycythemia Vera, Essential thrombocythemia, Chronic eosinophilic leukemia, Juvenile myelomonocytic leukemia

APPROVED BY GOVERNING BODIES:

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 (CFR)Title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply.  Refer to member’s benefit plan.

CURRENT CODING:

CPT Codes:

38204	Management of recipient hematopoietic cell donor search and cell acquisition
38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, allogeneic
38208	; thawing of previously frozen harvest, without washing, per donor
38209	; thawing of previously frozen harvest with washing per donor
38210	; specific cell depletion with harvest, T cell depletion
38211	; tumor cell depletion
38212	; red blood cell removal
38213	; platelet depletion
38214	; plasma (volume) depletion
38215	; cell concentration in plasma, mononuclear, or buffy coat layer
38230	Bone marrow harvesting for transplantation: allogeneic
38240	Bone marrow or blood-derived peripheral stem-cell transplantation: allogeneic
86812-86821	Histocompatibility studies code range (e.g., for allogeneic transplant)

HCPCS:

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)

REFERENCES:

1. Akhtari M. When to treat myelodysplastic syndromes. Oncology (Williston Park). May 2011; 25(6):480-486. 
2. Akin, Cem. Indolent and smoldering systemic mastocytosis: management and prognosis. In: Feldweg M, Anna & Rosmarin, Alan, ed. UpToDate. Waltham, Mass.: UpToDate, 2024. www.uptodate.com/contents/indolent-and-smoldering-systemic-mastocytosis-management-and-prognosis?
3. Aoki K, Ishikawa T, Ishiyama K, et al. Allogeneic haematopoietic cell transplantation with reduced-intensity conditioning for elderly patients with advanced myelodysplastic syndromes: a nationwide study. Br J Haematol. Feb 2015; 168(3):463-466.
4. Ballen KK, Shrestha S, Sobocinski KA et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. Mar 2010; 16(3):358-367.
5. Barrett AJ and Savani BN. Allogeneic stem cell transplantation for myelodysplastic syndrome.  Semin Hematol. Jan 2008; 45(1):49-59.
6. Basquiera AL, Pizzi S, Correas AG, et al. Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: A multicenter experience from Argentina. Pediatr Blood Cancer. Jan 2015; 62(1):153-157
7. Basquiera AL, Rivas MM, Remaggi G, et al. Allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndrome: Experience of the Argentinean Group of Bone Marrow Transplantation (GATMO). Hematology. Apr 2016.
8. Beelen DW, Trenschel R, Stelljes M, et al. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MCFludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. Jan 2020; 7(1): e28-e39.
9. Bewersdorf JP, Sheth AH, Vetsa S, et al. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis-A Systematic Review and Meta-Analysis. Transplant Cell Ther. Oct 2021; 27(10): 873.e1-873.e13.
10. Blaise D, Vey N, Faucher C, et al. Current status of reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica. Apr 2007; 92(4):533-541.
11. Boehm A, Sperr WR, Kalhs P, et al. Long-term follow-up after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia: a single center experience. Wien Klin Wochenschr. Jan 2014; 126(1-2):23-29.
12. Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. Dec 12 2013; 122(25):4047-4053.
13. Damaj G, Mohty M, Robin M, et al. Upfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Biol Blood Marrow Transplant. Sep 2014; 20(9):1349-1355.
14. Deeg HJ, Bartenstein M. Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: current status. Arch Immunol Ther Exp (Warsz). Feb 2012; 60(1):31-41.
15. Deeg HJ, Sandmaier BM. Who is fit for allogeneic transplantation? Blood. Dec 02 2010; 116(23):4762-4770.
16. Deschler B, de Witte T, Mertelsmann R, et al. Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: Problems and approaches. Haematologica. Nov 2006; 91(11):1513-1522.
17. Di Stasi A, Milton DR, Poon LM, et al. Similar transplant outcomes for AML/MDS patients with haploidentical versus 10/10 HLA matched unrelated and related donors. Biol Blood Marrow Transplant. Dec 2014; 20(12):1975-1981.
18. Food and Drug Administration. FDA approves fedratinib for myelofibrosis. August 2019. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fedratinib-myelofibrosis.   
19. Garcia-Manero G. Myelodysplastic syndromes: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. Jul 2012; 87(7):692-701. 
20. Gotlib, Jason. Advanced systemic mastocytosis: manangement and prognosis. In: Feldweg M, Anna & Rosmarin, Alan, ed. UpToDate. Waltham, Mass.: UpToDate, 2024. www.uptodate.com/contents/advanced-systemic-mastocytosis-management-and-prognosis?
21. Giralt SA, Horowitz M, Weisdorf D et al. Review of stem-cell transplantation for myelodysplastic syndromes in older patients in the context of the decision memo for Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome emanating from the Centers for Medicare and Medicaid Services. J Clin Oncol. Feb 10 2011; 29(5):566-572.
22. Gupta V, Kroger N, Aschan J et al. A retrospective comparison of conventional intensity conditioning and reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis. Bone Marrow Transplant. Sep 2009; 44(5):317-320.
23. Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. N Engl J Med. Mar 01 2012; 366(9):787-798.
24. Heidenreich S, Ziagkos D, de Wreede LC, et al. Allogeneic Stem Cell Transplantation for Patients Age >/= 70 Years with Myelodysplastic Syndrome: A Retrospective Study of the MDS Subcommittee of the Chronic Malignancies Working Party of the EBMT. Biol Blood Marrow Transplant. Jan 2017; 23(1):44-52.
25. Huisman C, Meijer E, Petersen EJ, et al. Hematopoietic stem cell transplantation after reduced intensity conditioning in acute myelogenous leukemia patients older than 40 years. Biol Blood Marrow Transplant. Feb 2008; 14(2):181-186.
26. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
27. Kanate AS, Majhail NS, Savani BN, et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. Jul 2020; 26(7): 1247- 1256.
28. Kasner MT and Luger SM. Update on therapy for myelodysplastic syndrome. Am J Hematol. Mar 2009; 84(3):177-186.
29. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. Jul 2022; 36(7): 1703-1719.
30. Kim H, Lee JH, Joo YD et al. A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome. Ann Hematol. Sep 2012; 91(9):1459- 1469.
31. Kindwall-Keller T and Isola LM. The evolution of hematopoietic SCT in myelodysplastic syndrome. Bone Marrow Transplant. Apr 2009; 43(8):597-609.
32. Koenecke C, Gohring G, de Wreede LC, et al. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation. Haematologica. Mar 2015; 100(3):400-408.
33. Kroger N. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood. Jun 14 2012; 119(24):5632-5639.
34. Kroger N, Bornhauser M, Ehninger G, et al. Allogeneic stem cell transplantation after a fludarabine/busulfan based reduced intensity conditioning inpatients with myelodysplastic syndromes or secondary acute myeloid leukemia. Ann Hematol. Jun 2003; 82(6):336-342.
35. Kröger N, Iacobelli S, Franke GN, et al. Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial). J Clin Oncol. Jul 01 2017; 35(19): 2157-2164.
36. Laport GG, Sandmaier BM, Storer BE, et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant. Feb 2008; 14(2):246-255.
37. Martino R, Caballero R, Simon JA, et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes. Blood. Sept 15 2002; 100(6):2243-2245.
38. McLornan DP, Mead AJ, Jackson G, et al. Allogeneic stem cell transplantation for myelofibrosis in 2012. Br J Haematol. May 2012; 157(4):413-425.
39. Mesa RA. Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders. Hematology (Am Soc Hematol Educ Program) 2007; 2007:355-362. 
40. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes, Version 3.2023. www.nccn.org/professionals/physician_gls/pdf/mds.pdf.
41. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms, Version 3.2023. www.nccn.org/professionals/physician_gls/pdf/mpn.pdf. 
42. Oliansky DM, Antin JH, Bennett JM et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of myelodysplastic syndromes: an evidence-based review. Biol Blood Marrow Transplant. Feb 2009; 15(2):137-172.
43. Onida F, Brand R, van Biezen A, et al. Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from Human Leukocyte Antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party. Haematologica. Oct 2014; 99(10):1582-1590.
44. Oran B, Kongtim P, Popat U, et al. Cytogenetics, donor type, and use of hypomethylating agents in myelodysplastic syndrome with allogeneic stem cell transplantation. Biol Blood Marrow Transplant. Oct 2014; 20(10):1618-1625.
45. Pohlen M, Groth C, Sauer T, et al. Outcome of allogeneic stem cell transplantation for AML and myelodysplastic syndrome in elderly patients (60 years). Bone Marrow Transplant. Nov 2016; 51(11):1441-1448.
46. Robin M, de Wreede LC, Padron E, et al. Role of allogeneic transplantation in chronic myelomonocytic leukemia: an international collaborative analysis. Blood. Sep 22 2022; 140(12): 1408-1418.
47. Schanz J, Tuchler H, Sole F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. Mar 10 2012; 30(8):820-829.
48. Scott BL, Pasquini MC, Fei M, et al. Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes-Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial. Transplant Cell Ther. Jun 2021; 27(6): 483.e1-483.e6.
49. Scott BL, Pasquini MC, Logan BR, et al. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. Apr 10 2017; 35(11): 1154-1161.
50. Song Y, Yin Z, Ding J, et al. Reduced Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation Is a Good Choice for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials. Front Oncol. 2021; 11: 708727.
51. Symeonidis A, van Biezen A, de Wreede L, et al. Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol. Oct 2015;171(2): 239-246.
52. Tauro S, Craddock C, Peggs K, et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol. Dec 20 2005; 23(36):9387-9393.
53. Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol. Feb 10 2011; 29(5):573-582.
54. Valcarcel D and Martino R. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and acute myelogenous leukemia. Current Opin Oncol. Nov 2007; 19(6):660-666.
55. Valcarcel D, Martino R, Caballero D, et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol. Feb 01 2008; 26(4):577-584.
56. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. Mar 1 2012; 366(9):799-807.
57. Yoshimi A, Strahm B, Baumann I, et al. Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia. Biol Blood Marrow Transplant. Mar 2014; 20(3):425-429.
58. Zeng W, Huang L, Meng F, et al. Reduced-intensity and myeloablative conditioning allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome: a meta-analysis and systematic review. Int J Clin Exp Med. 2014; 7(11):4357-4368.

POLICY HISTORY:

Medical Policy Panel, June 2009

Medical Policy Group, June 2009 (2)

Medical Policy Administration Committee, July 2009

Available for comment July 1-August 14, 2009

Medical Policy Group, December 2011 (3): 2012 Code verbiage changes for 38208, 38209, 38230 & added new code 38232

Medical Policy Group, February 2012 (2): Updated Key Points, References

Medical Policy Group, November 2012 (4): Title Change, added the word

“Hematopoietic”, Updated Key Points, References.  Policy statement remained unchanged.

Medical Policy Panel, November 2013

Medical Policy Group, November 2013 (3): Updated description, key points and references; no change in policy statement

Medical Policy Panel, November 2014

Medical Policy Group, November 2014 (3): Updates to Description, Key Points, and References. No change in policy statement.

Medical Policy Panel, January 2016

Medical Policy Group, April 2016 (2): Updates to Description, Key Points, Key Words, and References, removed codes 86812-86822 from Current Coding; added myeloablative to allogeneic HSCT in policy; no change in intent of coverage.

Medical Policy Panel, January 2017

Medical Policy Group, March 2017 (7): 2017 Updates to Title, Description, Key Points, Key Words, and References. No change in policy statement.

Medical Policy Panel, January 2018

Medical Policy Group, (7): Updates to Description, Key Points, Coding and References.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): 2019 Updates to Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, January 2020

Medical Policy Group, March 2020 (3): 2020 Updates to Description, Key Points, Practice Guidelines and Position Statements, References and Key Words: added: Systemic Mastocytosis, Aggressive systemic mastocytosis (ASM), Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), Mast cell sarcoma (MCS) and Mast cell leukemia (MCL). Added Systemic Mastocytosis as a covered diagnosis for allogeneic stem cell transplant with criteria for coverage. Available for comment: March 5, 2020 through April 18, 2020. No other changes to policy statement or intent.

Medical Policy Panel, January 2021

Medical Policy Group, February 2021 (3): 2021 Updates to Key Points and Practice Guidelines and Position Statements. Policy statement updated to remove “not medically necessary,” no change to policy statement or intent.

Medical Policy Panel, January 2022

Medical Policy Group, February 2022 (3): 2022 Updates to Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, January 2023

Medical Policy Group, February 2023 (3): 2023 Updates to Description, Key Points, Practice Guidelines and Position Statements, References, and Key Words: added new World Health Organization Classifications: Acute leukemias of ambiguous lineage (ALAL), Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), Clonal hematopoiesis (CH), Clonal hematopoiesis of indeterminate potential (CHIP), Clonal cytopenia of undetermined significance (CCUS), Chronic myelomonocytic leukemia (CMML), Cutaneous mastocytosis, Chronic neutrophilic leukemia (CNL), Polycythemia vera, Essential thrombocythemia, Chronic eosinophilic leukemia, Juvenile myelomonocytic leukemia. No changes to policy statement or intent.

Medical Policy Panel, January 2024

Medical Policy Group, January 2024 (3): 2024 Updates to Policy statement -clarified RIC conditions treatment and removed the effective date information for systemic mastocytosis. Updates to Description, Key Points, Approved  by Governing Bodies, Benefits Application, and References. Current codes- removed code 38232 due to it is related to autologous transplant. No changes to the policy intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.