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Hematopoietic stem cell transplantation (HSCT) is an established treatment for certain hematologic malignancies and has been investigated for a variety of adult solid tumors. Interest continues in exploring nonmyeloablative allogeneic HSCT for a graft-versus-tumor effect of donor-derived T cells in metastatic solid tumors.
Hematopoietic Stem-Cell Transplantation
Hematopoietic stem-cell transplantation (HSCT) 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 radiotherapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood 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 Umbilical Cord Blood as a Source of Stem Cells policy.
Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HSCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic HSCT. Compatibility is established by typing of human leukocyte antigens (HLAs) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the HLA-A, -B, and -DR (antigen-D related) 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 (with the exception of umbilical cord blood).
Conventional Preparative Conditioning for HSCT
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 mediated by non-self immunologic effector cells that develop 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, immunosuppressant drugs are required to minimize graft rejection and GVHD, which also increases susceptibility of the patient to opportunistic infections. The immune reactivity between donor T cells and malignant cells that is responsible for the GVM effect also leads to acute and chronic GVHD.
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 HSCT
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 reduced-intensity conditioning 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 reduced-intensity conditioning remains arbitrary, with numerous versions employed, all seek to balance the competing effects of NRM and relapse due to residual disease. Reduced-intensity conditioning 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 reduced-intensity conditioning 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, reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative, as opposed to fully myeloablative (conventional) regimens.
HSCT in Solid Tumors in Adults
HSCT is an established treatment for certain hematologic malignancies. Its use in solid tumors is less well established, although it has been investigated for a variety of solid tumors. With the advent of nonmyeloablative allogeneic transplant, interest has shifted to exploring the generation of alloreactivity to metastatic solid tumors via a graft-versus-tumor effect of donor-derived T cells.
HSCT as a treatment either of breast cancer, ovarian cancer, germ cell tumors, ependymoma, or malignant glioma is addressed in separate policies, Hematopoietic Stem-Cell Transplantation for Breast Cancer, Hematopoietic Stem-Cell Transplantation for Epithelial Ovarian Cancer, Hematopoietic Stem-Cell Transplantation in the Treatment of Germ-Cell Tumors, Hematopoietic Stem-Cell Transplantation for CNS Embryonal Tumors and Ependymoma, Autologous Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas, respectively. This policy collectively addresses other solid tumors of adults for which HSCT has been investigated, including lung cancer; malignant melanoma; tumors of the gastrointestinal tract (affecting the colon, rectum, pancreas, stomach, esophagus, gallbladder, or bile duct); male and female genitourinary systems (e.g., renal cell carcinoma, prostate cancer, cervical cancer, uterine cancer, fallopian tube cancer); tumors of the head and neck; soft tissue sarcoma; thyroid tumors; tumors of the thymus; and tumors of unknown primary origin.
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.
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.
Autologous or allogeneic hematopoietic stem cell transplant is considered investigational for the following malignancies:
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.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
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 # 8.01.24 per approval by Medical Policy Advisory Committee (MPAC)
7/19/2004: Code Reference section completed
11/18/2004: Reviewed by MPAC, no changes
10/20/2005: Code Reference section updated, codes 38230, G0355-G0364 added, J9000-J9999 deleted; ICD9 procedure codes 41.02, 41.03, 41.04, 41.09 added
3/15/2006: Coding updated. CPT4/HCPCS 2006 revisions added to policy.
9/18/2007: Policy reviewed, no changes
12/19/2007: Coding updated per 2008 CPT/HCPCS revisions
9/26/2008: Policy description updated, policy statements unchanged. "High-dose chemotherpay" term removed from title
1/6/2009: Policy reviewed, "prior authorization before evaluation" deleted
04/26/2010: Policy title revised to change “Stem-Cell Support” to “Stem-Cell Transplantation.” Policy description updated regarding conventional preparative conditioning and reduced-intensity conditioning for HSCT; however, the policy statement was unchanged. FEP verbiage added to the Policy Exceptions section. Added new CPT codes 86825 and 86826. Deleted HCPCS G0265, G0266, and G0267 from the code section as these codes were deleted on 12/31/2007. Added HCPCS S2140 and S2142 to the non-covered table.
10/21/2010: Policy reviewed; no changes.
10/05/2011: Policy reviewed; no changes.
12/13/2012: Policy reviewed; no changes.
01/22/2014: Policy reviewed; no changes.
12/11/2014: Policy reviewed; description updated. Policy statements unchanged.
08/27/2015: Code Reference section updated to add ICD-10 codes, updated the code descriptions for 38240, 38241, and 38242; removed deleted HCPCS code G0363, and removed deleted code CPT 96445 and replaced with CPT code 96446.
04/04/2016: Policy description updated regarding FDA regulations. Policy statement updated to make minor changes: 1) "allogeneic stem cell" changed to "allogeneic hematopoietic stem cell" and 2) "Pancreas cancer" changed to "Pancreatic cancer." Investigative definitions updated in policy guidelines.
05/25/2016: Policy number added.
Blue Cross Blue Shield Association policy # 8.01.24
This may not be a comprehensive list of procedure codes applicable to this policy.