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DESCRIPTIONHematopoietic Stem-Cell Transplantation
Hematopoietic stem-cell transplantation (SCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. Bone-marrow stem cells may be obtained from the transplant recipient (i.e., autologous SCT) or from a donor (i.e., allogeneic SCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naïve” and thus are associated with a lower incidence of rejection or graft-versus-host disease (GVHD). Cord blood is discussed in greater detail in the Placental and Umbilical Cord Blood as a Source of Stem Cells policy.
Immunologic compatibility between infused stem cells and the recipient is not an issue in autologous SCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic SCT. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the HLA A, B, and DR loci on each leg of chromosome 6. Depending on the disease being treated, an acceptable donor will match the patient at all or most of the HLA loci.
Conventional Preparative Conditioning for Hematopoietic SCT
The conventional (“classical”) practice of allogeneic HSCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to destroy endogenous hematopoietic capability 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 that develops after engraftment of allogeneic stem cells within the patient’s bone marrow space. While the slower GVM effect is considered to be the potentially curative component, it may be overwhelmed by extant disease without the use of pretransplant conditioning. However, intense conditioning regimens are limited to patients who are sufficiently fit medically to tolerate substantial adverse effects that include pre-engraftment opportunistic infections secondary to loss of endogenous bone marrow function and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allogeneic HSCT, immune suppressant drugs are required to minimize graft rejection and GVHD, which also increases susceptibility of the patient to opportunistic infections.
The success of autologous HSCT is predicated on the ability of cytotoxic chemotherapy with or without radiation to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic stem cells obtained from the patient prior to undergoing bone marrow ablation. As a consequence, autologous HSCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HSCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not GVHD.
Reduced-Intensity Conditioning for Allogeneic SCT
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 conventional full-dose myeloablative conditioning treatments. The goal of RIC is not only to reduce disease burden, but also to minimize as much as possible associated treatment-related morbidity and nonrelapse mortality (NRM) in the period during which the beneficial GVM effect of allogeneic transplantation develops. Although the definition of RIC remains arbitrary, with numerous versions employed, all seek to balance the competing effects of NRM and relapse due to residual disease. RIC regimens can be viewed as a continuum in effects, from nearly totally myeloablative, to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allogeneic HSCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism, which may be supplemented with donor lymphocyte infusions to eradicate residual malignant cells. For the purposes of this Policy, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative, as opposed to fully myeloablative (conventional) regimens.
Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML) is a hematopoietic stem-cell disorder that is characterized by the presence of a chromosomal abnormality called the Philadelphia chromosome, which results from reciprocal translocation between the long arms of chromosomes 9 and 22. This cytogenetic change results in constitutive activation of BCR-ABL, a tyrosine kinase (TK) that stimulates unregulated cell proliferation, inhibition of apoptosis, genetic instability, and perturbation of the interactions between CML cells and the bone marrow stroma only in malignant cells.
The natural history of the disease consists of an initial (indolent) chronic phase, lasting a median of 3 years, that typically transforms into an accelerated phase, followed by a "blast crisis," which is usually the terminal event. Conventional-dose regimens used for chronic-phase disease can induce multiple remissions and delay the onset of blast crisis to a median of 4–6 years. However, successive remissions are invariably shorter and more difficult to achieve than their predecessors.
Imatinib mesylate (Gleevec®), a selective inhibitor of the abnormal BCR-ABL TK protein, is considered the treatment of choice for newly diagnosed CML. While imatinib can be highly effective in suppressing CML in most patients, it is not curative and is ineffective in 20% to 30%, initially or due to development of BCR-ABL mutations that cause resistance to the drug. Two other TK inhibitors (TKIs, dasatinib, nilotinib) have received marketing approval from the U.S. Food and Drug Administration (FDA) to treat CML following failure or patient intolerance of imatinib. In any case, allogeneic SCT remains the only treatment capable of inducing durable remissions or cure in CML patients.
POLICYNo benefits will be provided for a covered transplant procedure unless the Member receives prior authorization through Case Management from Blue Cross & Blue Shield of Mississippi.
Allogeneic stem-cell transplantation (SCT) may be considered medically necessary as a treatment of chronic myelogenous leukemia.
Reduced-intensity conditioning (RIC) allogenic SCT may be considered medically necessary as a treatment of chronic myelogenous leukemia in patients who meet clinical criteria for an allogeneic SCT but who are not considered candidates for a myeloablative conditioning allogeneic SCT.
Autologous SCT is investigational as a treatment of chronic myelogenous leukemia.
POLICY EXCEPTIONSFor 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 GUIDELINESSome patients for whom a conventional myeloablative allotransplant could be curative may be considered candidates for reduced-intensity conditioning (RIC) allogeneic SCT. These include patients 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 use of a standard myeloablative conditioning regimen.
Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY3/25/2004: 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 # 8.01.30 per approval by Medical Policy Advisory Committee (MPAC)
6/25/2004: Code Reference section completed
11/18/2004: Reviewed by MPAC; no changes
10/27/2005: Code Reference section updated; Covered table - CPT-4 codes 38230 added, ICD-9 Procedure 41.02, 41.03 added, HCPCS G0355, G0356, G0357, G0358, G0359, G0360, G0361, G0362, G0363, G0364 added, J9000-J9999 deleted; Non-Covered table - ICD-9 41.01, 41.09 added
3/16/2006: Coding updated. CPT4/HCPCS 2006 revisions added to policy
5/21/2007: Policy reviewed, no changes
12/19/2007: Coding updated per 2008 CPT/HCPCS revisions
7/22/2008: Policy updated; terminology modified but materially unchanged. High dose chemotherapy terminology removed from title and policy statement and replaced with stem cell transplantation (SCT). Policy statement added; reduced-intensity conditioning (RIC) allogeneic SCT is considered investigational as treamtent of chronic myelogenous leukemia in those who do not qualify for a myeloablative allogeneic SCT.
9/12/2008: Code reference section updated per the annual ICD-9 updates effective 10-1-2008
1/6/2009: Policy reviewed, "prior authorization before evaluation" deleted
04/26/2010: Policy description updated regarding conventional and RIC allogeneic SCT. Policy statement revised to indicate that SCT using a RIC regimen may be considered medically necessary in patients who meet clinical criteria for an allogeneic SCT but who are not considered candidates for a myeloablative conditioning allogeneic SCT. The policy guidelines were updated based on the revised statement. FEP and State and School Employee verbiage added to the Policy Exceptions section. Added new CPT codes 86825 and 86826 and HCPCS S2140 and S2150. Deleted HCPCS G0265, G0266, and G0267 from the code section as these codes were deleted on 12/31/2007.
02/23/2011: Policy reviewed; no changes.
01/19/2012: Policy reviewed; no changes.
04/03/2013: Policy reviewed; no changes.
03/10/2014: Policy reviewed; no changes.
Blue Cross Blue Shield Association policy # 8.01.30
CODE REFERENCEThis 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.