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Most patients with autoimmune disorders respond to conventional therapies. However, these drugs are not curative, and a proportion of patients will have severe, recalcitrant, or rapidly progressive disease. It is in this group of patients with severe autoimmune disease that alternative therapies have been sought, including hematopoietic stem cell transplantation (HSCT).
Autoimmune diseases represent a heterogeneous group of immune-mediated disorders, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis/scleroderma, and chronic immune demyelinating polyneuropathy. The National Institutes of Health estimates that 5%–8% of Americans have an autoimmune disorder.
The pathogenesis of autoimmune diseases is not well-understood, but appears to involve underlying genetic susceptibility and environmental factors that lead to loss of self-tolerance, culminating in tissue damage by the patient’s own immune system (T cells).
Immune suppression is a common treatment strategy for many of these diseases, particularly the rheumatic diseases (e.g., RA, SLE, and scleroderma). Most patients with autoimmune disorders respond to conventional therapies, which consist of anti-inflammatory agents, immunosuppressants, and immunomodulating drugs. However, these drugs are not curative, and a proportion of patients will have severe, recalcitrant, or rapidly progressive disease. It is in this group of patients with severe autoimmune disease that alternative therapies have been sought, including hematopoietic stem-cell transplantation (SCT). The primary concept underlying use of HSCT for these diseases is that ablating and “resetting” the immune system can alter the disease process, first inducing a sustained remission that possibly leads to cure.
Hematopoietic 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 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 SCT) or from a donor (allogeneic SCT). 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 and 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 (HLA) using cellular, serologic, or molecular techniques. HLA refers to the tissue type expressed at the class I and class II loci on 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).
Autologous Stem-Cell Transplantation for Autoimmune Diseases
The goal of autologous HSCT in patients with autoimmune diseases is to eliminate self-reactive lymphocytes (lymphoablation) and generate new self-tolerant lymphocytes. This approach is in contrast to destroying the entire hematopoietic bone marrow (myeloablation), as is often performed in autologous HSCT for hematologic malignancies. However, no standard conditioning regimen exists for autoimmune diseases, and both lymphoablative and myeloablative regimens are used. The efficacy of the different conditioning regimens has not been compared in clinical trials.
Currently, for autoimmune diseases, autologous transplant is preferred over allogeneic, in part because of the lower toxicity of autotransplant relative to allogeneic, the graft-versus-host disease associated with allogeneic transplant, and the need to administer post-transplant immunosuppression after an allogeneic transplant.
Allogeneic Stem-Cell Transplantation for Autoimmune Diseases
The experience of using allogeneic HSCT for autoimmune diseases is currently limited, but has two potential advantages over autologous transplant. First, the use of donor cells from a genetically different individual could possibly eliminate genetic susceptibility to the autoimmune disease and potentially result in a cure. Second, there exists a possible graft-versus-autoimmune effect, in which the donor T cells attack the transplant recipient’s autoreactive immune cells.
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.
No 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.
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 # 8.01.25 per approval by Medical Policy Advisory Committee (MPAC)
6/25/2004: Code Reference section completed
11/18/2004: Reviewed by MPAC, no changes
10/19/2005: Code Reference section updated, codes G0355-G0364 added, 38204, 38205, 38240, 38242, 86812-86822, J9000-J9999 deleted; ICD9 procedure code 41.01, 41.09 added, 41.05, 41.08, 41.91 deleted; description of ICD9 procedure code 99.79 revised; HCPCS statement added on how to report J9000-J9999 codes.
03/10/2006: 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
9/30/2008: Description updated, "high-dose chemotherapy" removed from policy title and statement. "Stem-cell support" wording replaced with "stem-cell transplantation". No changes to policy statement intent.
10/05/2011: Policy statement revised to add juvenile idiopathic arthritis and type 1 diabetes mellitus as investigational indications.
11/30/2012: Policy reviewed; no changes.
01/22/2014: Added chronic inflammatory demyelinating polyneuropathy as an investigational indication.
11/14/2014: Policy reviewed; description updated. Policy statement revised to change "stem-cell support" to "hematopoietic stem-cell transplantation" and state that autologous or allogeneic hematopoietic stem-cell transplantation is considered investigational. Policy intent unchanged.
08/21/2015: Code Reference section updated to add ICD-10 codes, removed deleted HCPCS code G0363, and removed deleted code CPT 96445 and replaced with CPT code 96446.
03/09/2016: Policy description updated regarding FDA regulations. Policy statement unchanged. Investigative definition updated in policy guidelines section.
05/25/2016: Policy number added.
SOURCE(S)Blue Cross Blue Shield Association policy # 8.01.25
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.