BlueCross and BlueShield of Montana Medical Policy/Codes
Stem-Cell Transplant for Myelodysplastic Syndromes and Myeloproliferative Diseases
Chapter: Transplant
Current Effective Date: December 27, 2013
Original Effective Date: May 03, 2012
Publish Date: September 27, 2013
Revised Dates: September 16, 2013
Description

Myelodysplastic Syndrome (MDS)

MDS refers to a heterogeneous group of clonal hematopoietic disorders characterized by impaired maturation of hematopoietic cells and a tendency to transform into acute myelocytic leukemia (AML).  MDS can occur as a primary (i.e., idiopathic form), or be secondary to cytotoxic therapy, ionizing radiation, or other environmental insult.  Chromosomal abnormalities are seen in 40%–60% of patients, frequently involving deletions of chromosome five or seven, or an extra chromosome (i.e., trisomy eight).  The most widely accepted classification system for MDS is the French-American-British (FAB) system that identifies five types of MDS with increasing numbers of circulating blast cells as follows:

  • Refractory anemia (RA)
  • Refractory anemia with ringed sideroblasts (RARS)
  • Refractory anemia with excess blasts (RAEB)
  • Refractory anemia with excess blasts in transformation (RAEBT)
  • Chronic myelomonocytic leukemia (CMML)

Patients either succumb to disease progression to 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.

Megakaryocytic Thrombocytopenia (MT) is a condition of abnormally large thromboctyes in the bone marrow, causing blood clotting and platelet deficiencies.  This is possibly related to Noonan’s syndrome, also known as Male Turner’s Syndrome. 

Myeloproliferative Disorders

The myeloproliferative disorders are characterized by the slow but relentless expansion of a clone of cells with the potential evolution into a blast crisis similar to AML.  Myeloproliferative disorders include the following:

  • Polycythemia vera (PV) is characterized by an expansion of the total red cell mass.  Initial treatment focuses on phlebotomy to reduce red cell mass and viscosity.  However, the disease inevitably progresses and after a medial survival of 15 years, patients typically succumb to thrombotic complications or leukemic evolution.
  • Essential thrombocythemia (ET) is characterized by an isolated expansion of the megakaryocytic lineage.  The median survival is 10 years with most deaths due to thrombotic complications.
  • Agnogenic myeloid metaplasia with myelofibrosis, also known as primary myelofibrosis is characterized by marrow fibrosis, splenomegaly, and extramedullary hematopoiesis.
Policy

Each benefit plan or contract defines which services are covered, which are excluded, and which are subject to dollar caps or other limits.  Members and their providers have the responsibility for consulting the member's benefit plan or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan or contract, the benefit plan or contract will govern.

 Coverage

Coverage for evaluation of and subsequent single treatment by stem-cell transplant (SCT) (using bone marrow, peripheral blood, or umbilical cord blood as a stem-cell source), derived from a specific donor category, and following a chemotherapy regimen for treatment of Myelodysplastic Syndromes and Myeloproliferative Diseases are identified in the grids below.

Myelodysplastic Syndromes including:

  • Refractory Anemias,
  • Chronic Myelomonocytic Leukemia,
  • Megakaryocytic Thrombocytopenia (MT).

Allogeneic

May be considered medically necessary:

  • in patients with increasing numbers of blasts, signaling a possible transformation to acute myeloid leukemia;
  • in patients with refractory anemia with or without ringed sideroblasts when chromosomal abnormalities are present or the disorder is associated with the development of significant cytopenias.

Autologous

Is considered experimental, investigational and unproven.

Tandem or Triple Stem-Cell Transplant

Is considered experimental, investigational and unproven. 

Donor Leukocyte Infusion

Is considered experimental, investigational and unproven. 

Myeloproliferative Diseases including:

  • Polycythemia Vera (PV),
  • Essential Thrombocythemia (ET),
  • Agnogenic Myeloid Metaplasia with Myelofibrosis (Primary Myelofibrosis).

Allogeneic

May be considered medically necessary:

  • when there is progression to myelofibrosis;
  • when there is evolution toward acute leukemia; or
  • in patients with ET with an associated thrombotic or hemorrhagic disorder.

Autologous

Is considered experimental, investigational and unproven.

Tandem or Triple Stem-Cell Transplant

Is considered experimental, investigational and unproven. 

Donor Leukocyte Infusion

Is considered experimental, investigational and unproven. 

Rationale

The quality of life after high-dose chemotherapy (HDC) followed by hematopoietic stem-cell (HSC) (i.e., blood or marrow) transplant is of utmost importance.  In aplastic anemia and malignancies, there is the expectation of improved status after HDC and HSC.  Conversely, quality of life outcomes (measured by growth, skeletal development dysfunction, and neuropsychological) for patients with storage diseases is gradually being defined.  Because of these long-term problems, non-malignant or maldevelopment indications for HDC and HSCs should not be reviewed with criteria similar to that for malignancies.

Myelodysplastic Syndrome (MDS)

The policy on MDS is based in part on a 1992 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment that focused on alloSCT (allogeneic stem cell transplant) as a treatment of MDS.  The following conclusions were offered:

  • AlloSCT appears to improve health outcome of selected patients with MDS.  The largest study showed an overall survival of 45% at three years.
  • Compared to conventional therapy, consisting of supportive therapy, survival after alloSCT can be considered at least as good.

The 1992 BCBSA TEC Assessment did not address myeloproliferative disorders.

Myeloproliferative Disorders (MPD)

Due to the prolonged natural history of both polycythemia vera (PV) or essential thrombocythemia, and the older average age of onset (60 years), alloSCT has not been extensively studied in these patients.  A 1998 review from Thomas' Hematopoietic Cell Transplantation textbook, reported only nine patients with PV had been treated with alloSCT.  However, considering that PV represents an emerging malignant clone of cells, and the success of alloSCT in other hematopoietic disorders, it seems reasonable to extrapolate the results of this approach for myelodysplastic syndrome to PV.  There has been more research in agnogenic myeloid metaplasia (AMM, also called myelofibrosis) since this disorder may also occur in children.  In addition, the short median survival of AMM compared to other myeloproliferative disorders has prompted earlier consideration of high-dose chemotherapy.  In one review of a total of 29 patients reported in the literature at the time, 16 patients were alive without evidence of relapsed disease between seven months and 15 years after transplant.

2007 National Comprehensive Cancer Network (NCCN) Guidelines

The 2007 NCCN treatment guidelines (V.1.2007) for MDS suggest alloSCT from an HLA (human leukocyte antigens)-matched sibling donor is a preferred approach, in particular for those with high-risk disease.  The guidelines also suggest RIC (reduced-intensity conditioning) regimens and matched unrelated donor SCTs are becoming options at some centers.  However, the NCCN states that comparative clinical trials are needed to determine the role of these approaches.

2007 National Cancer Institute (NCI) Clinical Trials Database (PDQ®)

The NCI PDQ database in 2007 identified the following active trials that involve stem-cell support for patients with MDS:

  • Phase II/III Combination Chemotherapy and Bone Marrow Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer (RPCI-RP-9815)
  • Phase II/III Stem Cell Transplantation for Hematological Malignancies (0005M52481)
  • Phase II/III Stem Cell Transplant for Bone Marrow Failures (9504M09637)
  • Phase III Filgrastim-Mobilized Peripheral Stem Cell Transplantation Compared With Bone Marrow Transplantation From Unrelated Donors in Treating Patients With Hematologic Malignancies (BMTCTN-0201)
  • Phase III Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia (AMLO2)
  • Phase III Biology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG) (AMLCG 99)

Additional Review of Literature Through 2008

No randomized, clinical trials have been identified subsequent to the last update on the use of myeloablative chemotherapy with alloSCT for MDS/AML (acute myelocytic leukemia).  However, a growing body of evidence from largely heterogeneous uncontrolled studies of RIC with alloSCT shows long-term remissions (>4 years) can be achieved, often with reduced treatment-related morbidity and mortality, in patients with MDS/AML who otherwise would not be candidates for myeloablative conditioning regimens.  In the absence of prospective, comparative, randomized trials, only indirect comparisons can be made between the relative clinical benefits and harms associated with myeloablative and RIC regimens with alloSCT. Furthermore, no randomized trials have been published in which RIC with alloSCT has been compared with conventional chemotherapy alone, which has been the standard of care in patients with MDS/AML for whom myeloablative chemotherapy and alloSCT are contraindicated.

Data on therapy for MPD remain sparse.  As outlined previously in this policy, with the exception of myeloablative chemotherapy and alloSCT, no therapy has yet been proven to be curative or to prolong survival of patients with MPD.  However, the significant toxicity of myeloablative conditioning and alloSCT in MPD has led to study of the use of RIC regimens for these diseases.  A recent series included 27 patients (mean age: 59 years) with MPD who underwent alloSCT using a RIC regimen of low-dose (2 Gy) total body irradiation alone or with the addition of fludarabine.  At a median follow-up of 47 months, the three year relapse-free survival was 37% and overall survival was 43%, with a three year nonrelapse mortality of 32%. While this approach has promise, data comparing outcomes of potentially curative myeloablative conditioning and alloSCT versus RIC and alloSCT are not available.

The 2008 NCCN treatment guidelines (V.2.2008) for myelodysplastic syndromes are unchanged from the 2007 version.

A 2008 search of the National Cancer Institute (NCI) Clinical Trials Database (PDQ®) database identified seven new active phase III trials that involve stem-cell support for patients with MDS/AML or MPD besides those outlined above in the previous update of this policy.  At least 12 phase II trials of various treatments for these diseases are actively recruiting patients.

Tandem or Triple Stem-Cell Transplant and Donor Leukocyte Infusion (DLI) for Myelodysplastic Syndromes and Myeloproliferative Diseases are considered experimental, investigational, and unproven due to lack of adequate evidence of safety and effectiveness documented in published, peer-reviewed medical literature.

Coding

Disclaimer for coding information on Medical Policies           

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

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

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

Rationale for Benefit Administration
 
ICD-9 Codes

41.00, 41.01, 41.02, 41.03, 41.04, 41.05, 41.06, 41.07, 41.08, 41.09, 41.91, 99.25, 99.74, 99.79, 238.72, 238.73, 238.74, 238.75, 238.76, 238.77, 238.79

ICD-10 Codes
C92.10 – C92.12, C92.20 – C92.22, C94.6, D45, D46.0-D46.9, D47.0 – D47.9, 30243G1, 30243X1, 30243Y1, 07DQ0ZZ, 07DQ3ZZ, 07DR0ZZ, 07DR3ZZ, 07DS0ZZ, 07DS3ZZ 
Procedural Codes: 36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38230, 38232, 38240, 38241, 38242, 38243, 81265, 81266, 81267, 81268, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86849, 86950, 86985, 88240, 88241, S2140, S2142, S2150
References
  1. Treatment of Myelodysplastic Syndrome with Allogeneic Bone Marrow Transplantation or Hematopoietic Growth Factors. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Program (1992 December):415-56.
  2. Anderson, J.E. Allogeneic hematopoietic cell transplantation for myelodysplastic and myeloproliferative disorders. In: Thomas ED, Blume KG, Forman SJ, eds. Hematopoietic Cell Transplantation. Malden, MA, Blackwell Science, Inc, (1999).
  3. Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem Cell Transplant. BCBSA Medical Policy Reference Manual (2005 September) Medicine: 2.03.03.
  4. Myelodysplastic Syndromes. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. v.1.2007. Available at www.nccn.org .
  5. Blaise, D., Vey, N., et al. Current status of reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica (2007) 92(4):533-41.
  6. Valcarcel, D., Martino, R. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and acute myelogenous leukemia. Current Opinions in Oncology (2007) 19(6):660-6.
  7. Mesa, R.A. Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders. Hematology (Am Soc Hematol Educ Program) (2007):355-62.
  8. Laport, G.G., Sandmaier, B.M., et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biology of Blood and Marrow Transplant (2008) 14(2):246-55.
  9. Myelodysplastic Syndromes. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. v.2.2008. Available at www.nccn.org .
  10. Huisman, C., Meijer, E., et al. Hematopoietic stem cell transplantation after reduced intensity conditioning in acute myelogenous leukemia patients older than 40 years. Biology of Blood and Marrow Transplantation (2008) 14(2):181-6.
  11. Barrett, A.J., Savani, B.N. Allogeneic stem cell transplantation for myelodysplastic syndrome. Seminars in Hematology (2008) 45(1):49-59.
  12. Valcarcel, D., Martino, R., 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. Journal of Clinical Oncology (2008) 26(4):577-84.
  13. Allogeneic Stem-Cell Transplantation for Myelodysplastic and Myeloproliferative Diseases.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 June) Therapy 8.01.21.
History
November 2011 New policy for BCBSMT
September 2013 Policy formatting and language revised.  Title changed from "Allogeneic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplams" to "Stem-Cell Transplant for Myelodysplastic Syndromes and Myeloproliferative Diseases".
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Stem-Cell Transplant for Myelodysplastic Syndromes and Myeloproliferative Diseases