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.
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.
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.