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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. Stem cells from bone marrow may be obtained from the transplant recipient (autologous SCT, auto-SCT) or from a donor (allogeneic SCT, allo-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. 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 auto-SCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allo-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 arm 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 SCT
The conventional (“classical”) practice of allogeneic SCT 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 SCT, 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 SCT 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 SCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous SCT 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 to reduce disease burden, but also to minimize as much as possible associated treatment-related morbidity and non-relapse 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 SCT 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 non-myeloablative, as opposed to fully myeloablative (conventional) regimens.
Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are neoplasms of hematopoietic origin characterized by the accumulation of lymphocytes with a mature, generally well-differentiated morphology. In CLL, these cells accumulate in blood, bone marrow, lymph nodes, and spleen, while in SLL they are generally confined to lymph nodes. The Revised European-American/WHO Classification of Lymphoid Neoplasms considers B-cell CLL and SLL a single disease entity.
CLL and SLL share many common features and are often referred to as blood and tissue counterparts of each other, respectively. Both tend to occur in older individuals and present as asymptomatic enlargement of the lymph nodes. Both tend to be indolent in nature but can undergo transformation to a more aggressive form of disease (e.g., Richter’s transformation).
Treatment regimens used for CLL are generally the same as those used for SLL, and outcomes of treatment are comparable for the 2 diseases. Both low- and intermediate-risk CLL and SLL demonstrate relatively good prognoses with median survivals of 6 to 10 years, while the median survival of high-risk CLL or SLL may be only 2 years. Although typically responsive to initial therapy, CLL and SLL are rarely cured by conventional therapy, and nearly all patients ultimately die of their disease. This natural history prompted investigation of hematopoietic stem-cell transplantation as a possible curative regimen.
POLICYNo benefits will be provided for a covered transplant procedure or a transplant evaluation unless the Member receives prior authorization through Case Management from Blue Cross & Blue Shield of Mississippi.
Allogeneic hematopoietic stem-cell transplantation may be considered medically necessary to treat chronic lymphocytic leukemia or small lymphocytic lymphoma in patients with markers of poor-risk disease (see Policy Guidelines and Rationale). Use of a myeloablative or reduced-intensity pretransplant conditioning regimen should be individualized based on factors that include patient age, the presence of comorbidities, and disease burden.
Allogeneic hematopoietic stem-cell transplantation is considered investigational to treat chronic lymphocytic leukemia or small lymphocytic lymphoma except as noted above.
Autologous hematopoietic stem-cell transplantation is considered investigational to treat chronic lymphocytic leukemia and small lymphocytic lymphoma.
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 GUIDELINESStaging and Prognosis of Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
Two scoring systems are used to determine stage and prognosis of patients with CLL/SLL. As outlined in Table 1, the Rai and Binet staging systems classify patients into 3 risk groups with different prognoses, and are used to make therapeutic decisions.
Table 1. Rai and Binet Classification for CLL/SLL
Because prognosis of patients varies within the different Rai and Binet classifications, other prognostic markers are used in conjunction with staging to determine clinical management. These are summarized in Table 2, according to availability in clinical centers.
Table 2. Markers of Poor Prognosis in CLL/SLL
Reduced-Intensity Conditioning for Allogeneic SCT
The ideal allogeneic donors are HLA-identical siblings, matched at the HLA-A, B, and DR loci (6 of 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 patient, where usually there is sharing of only 3 of the 6 major histocompatibility antigens. The majority of patients will have such a donor; however, the risk of GVHD and overall morbidity of the procedure may be severe, and experience with these donors is not as extensive as that with matched donors.
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 # 8.01.15 per approval by Medical Policy Advisory Committee (MPAC)
7/14/2004: Code Reference section completed
11/18/2004: Reviewed by MPAC: The phrase "either autologous or allogeneic" removed from the following statement: "High-dose chemotherapy with autologous stem cell support is considered investigational as a treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma." The following statement was added: "High-dose chemotherapy with allogeneic stem cell support is considered medically necessary for patients with T-cell disease." Code Reference section updated; Non-Covered table was split into two tables -- Covered and Non-Covered.
10/27/2005: Code Reference section updated: Covered table -- CPT-4 code 38230 added; ICD-9 Procedure codes 41.02, 41.03, HCPCS G0355, G0356, G0357, G0358, G0359, G0360, G0361, G0362, G0363, G0364 added, J9000-J9999 deleted; Non-Covered table -- ICD-9 Procedure codes 41.01, 41.09
3/22/2006: Coding policy updated. CPT4/HCPCS revisions added to policy.
12/20/2007: Coding updated per 2008 CPT/HCPCS revisions
9/29/2008: Description updated; terminology modified but materially unchanged. High dose chemotherapy terminology removed from title and policy statement and replaced with stem cell transplantation (SCT).
04/26/2010: Policy title revised to change “Stem-Cell Support” to “Stem-Cell Transplantation.” Policy description updated regarding treatment approaches. Policy statement changed to indicate that allogeneic hematopoietic stem-cell transplantation may be considered medically necessary to treat chronic lymphocytic leukemia or small lymphocytic lymphoma in patients with markers of poor-risk disease. Supporting explanations added to the policy guidelines. FEP and State and School Employee verbiage added to the Policy Exceptions section. Added new CPT codes 86825 and 86826. Also added HCPCS S2140 and S2142 to the covered table. Deleted HCPCS G0265, G0266, and G0267 from the code section as these codes were deleted on 12/31/2007.
04/19/2011: Policy reviewed; no changes.
03/02/2012: Policy reviewed; no changes.
04/04/2013: Policy reviewed; no changes.
03/12/2014: Policy reviewed; no changes.
SOURCE(S)Blue Cross Blue Shield Association policy # 8.01.15
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.