Hematopoietic Cell Transplantation for Autoimmune Diseases

POLICY NUMBER

A.8.01.25

DESCRIPTION

Most individuals with autoimmune disorders respond to conventional drug therapies. However, conventional drug therapies are not curative—and a proportion of individuals suffer from autoimmune diseases that range from severe to recalcitrant to rapidly progressive. It is in this group of individuals with a severe autoimmune disease that alternative therapies have been sought, including hematopoietic cell transplantation (HCT).

Autoimmune Disease Treatment

Immune suppression is a common treatment strategy for many autoimmune diseases, particularly rheumatic diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, and scleroderma). Most patients with autoimmune disorders respond to conventional therapies, which consist of anti-inflammatory agents, immunosuppressants, and immunomodulating drugs. However, conventional drug therapies are not curative, and a proportion of patients suffer from autoimmune diseases that range from severe to recalcitrant to rapidly progressive. It is for this group of patients with a severe autoimmune disease that alternative therapies have been sought, including hematopoietic cell transplantation (HCT). The primary concept underlying the use of HCT for these diseases is this: ablating and “resetting” the immune system can alter the disease process by inducing a sustained remission that possibly leads to cure. 

Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) is a procedure in which hematopoietic stem cells are intravenously infused to restore bone marrow and immune 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 HCT) or a donor (allogeneic HCT [allo-HCT]). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. Cord blood transplantation is discussed in 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 HCT. In allogeneic stem cell transplantation, immunologic compatibility between donor and patient is a critical factor for achieving a successful outcome. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques. The term HLA refers to the gene complex expressed at the HLA-A, -B, and -DR (antigen-D related) loci on each arm of chromosome 6. An acceptable donor will match the patient at all or most of the HLA loci.

Conditioning for Hematopoietic Cell Transplantation

Conventional Conditioning

The conventional (“classical”) practice of allo-HCT involves administration of cytotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to cause bone marrow ablation in the recipient. The beneficial treatment effect of this procedure is due to a combination of the initial eradication of malignant cells and subsequent graft-versus-malignancy (GVM) effect mediated by non-self-immunologic effector cells. While the slower GVM effect is considered the potentially curative component, it may be overwhelmed by existing disease in the absence of pretransplant conditioning. Intense conditioning regimens are limited to patients who are sufficiently medically fit to tolerate substantial adverse effects. These include opportunistic infections secondary to loss of endogenous bone marrow function and organ damage or failure caused by cytotoxic drugs. Subsequent to graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and graft-versus-host disease, which increases susceptibility to opportunistic infections.

The success of autologous HCT is predicated on the potential of cytotoxic chemotherapy, with or without radiotherapy, to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of the bone marrow with presumably normal hematopoietic stem cells obtained from the patient before undergoing bone marrow ablation. Therefore, autologous HCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HCT are also susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not GVH disease.

Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation

Reduced-intensity conditioning (RIC) refers to the pretransplant use of lower doses of cytotoxic drugs or less intense regimens of radiotherapy than are used in traditional full-dose myeloablative conditioning treatments. Although the definition of RIC is variable, with numerous versions employed, all regimens seek to balance the competing effects of relapse due to residual disease and non-relapse mortality. The goal of RIC is to reduce disease burden and to minimize associated treatment-related morbidity and non-relapse mortality in the period during which the beneficial GVM effect of allogeneic transplantation develops. Reduced-intensity conditioning regimens range from nearly total myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allo-HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism. In this policy, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative.

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 title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

POLICY

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.

Autologous hematopoietic cell transplantation is considered medically necessary as a treatment of systemic sclerosis (scleroderma) if all of the following conditions are met:

• adult individuals <60 years of age; AND

• maximum duration of condition of 5 years; AND

• modified Rodnan skin scores ≥15; AND

• internal organ involvement as noted in the Policy Guidelines; AND

• history of <6 months treatment with cyclophosphamide; AND

• no active gastric antral vascular ectasia; AND

• do not have any exclusion criteria as noted in the Policy Guidelines.

Autologous or allogeneic hematopoietic cell transplantation is considered investigational as a treatment of autoimmune diseases, including, but not limited to, the following:

• multiple sclerosis,

• systemic lupus erythematosus,

• juvenile idiopathic or rheumatoid arthritis,

• chronic inflammatory demyelinating polyneuropathy,

• type 1 diabetes.

Autologous hematopoietic cell transplantation as a treatment of systemic sclerosis/scleroderma not meeting the above criteria is considered investigational.

POLICY EXCEPTIONS

For 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 GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Autologous HCT should be considered for individuals with systemic sclerosis only if the condition is rapidly progressing and the prognosis for survival is poor. An important factor influencing the occurrence of treatment-related adverse effects and response to treatment is the level of internal organ involvement. If organ involvement is severe and irreversible, HCT is not recommended. Below are clinical measurements which can be used to guide the determination of organ involvement.

Individuals with internal organ involvement indicated by the following measurements may be considered for autologous HCT:

• Cardiac: abnormal electrocardiogram; OR

• Pulmonary: diffusing capacity of carbon monoxide (DLCo) <80% of predicted value; decline of forced vital capacity (FVC) of ≥10% in last 12 months; pulmonary fibrosis; ground glass appearance on high-resolution chest computed tomography (CT); OR

• Renal: scleroderma-related renal disease.

Individuals with internal organ involvement indicated by the following measurements should not be considered for autologous HCT:

• Cardiac: left ventricular ejection fraction <50%; tricuspid annular plane systolic excursion <1.8 cm; pulmonary artery systolic pressure >40 mm Hg; mean pulmonary artery pressure >25 mm Hg

• Pulmonary: DLCo <40% of predicted value; FVC <45% of predicted value

• Renal: creatinine clearance <40 ml/minute.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; andB.  appropriate with regard to standards of good medical practice; andC.  not solely for the convenience of the Member, his or her Provider; andD.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good 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. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

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.

POLICY HISTORY

3/25/2004: 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 hematopoieticstem-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 A.8.01.25 added.

08/08/2017: Policy title and statement updated to change "Hematopoietic Stem-Cell Transplantation" to "Hematopoietic Cell Transplantation." Policy description updated.

12/21/2017: Code Reference section updated to add new 2018 CPT code 38222. Revised code descriptions for CPT codes 38220 and 38221 effective 01/01/2018.

02/08/2018: Policy description updated. Policy statement unchanged.

05/16/2019: Removed systemic sclerosis/scleroderma as investigational. Added medically necessary statement that autologous hematopoietic cell transplantation (HCT) is considered medically necessary as a treatment of systemic sclerosis/scleroderma under the specified conditions. Added statement that autologous HCT as a treatment of systemic sclerosis/scleroderma not meeting the above criteria is considered investigational. Policy Exceptions updated regarding FEP and State and School Employee members. Policy Guidelines updated regarding clinical measurements used to guide the determination of organ involvement. Code Reference section updated to add CPT code 38232 and ICD-10 diagnosis codes M34.0 – M34.9 to the medically necessary codes table. Investigational codes table updated to add CPT codes 38205, 38230, 38240 and ICD-10 procedure codes 30243G2, 30243G3, 30243G4, 30243X2, 30243X3, 30243X4, 30243Y2, 30243Y3, and 30243Y4. Removed deleted HCPCS code G0364.

09/27/2019: Code Reference section updated to add new ICD-10 procedure codes 30243U2, 30243U3, and 30243U4, effective 10/01/2019.

02/21/2020: Policy description updated regarding hematopoietic cell transplantation and conditioning for hematopoietic cell transplantation. Medically necessary criteria updated to change "Rodnan Scale Scores >15" to "Rodnan Scale Scores ≥15." Investigational statement updated to change "type 1 diabetes mellitus" to "type 1 diabetes."

03/05/2021: Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

12/22/2021: Code Reference section updated to make note of deleted ICD-10 procedure codes.

02/17/2022: Policy description updated. Policy statements unchanged.

11/22/2022: Code Reference section updated to remove deleted ICD-10 procedure codes 30230G0, 30240G0, 30230Y0, and 30240Y0.

02/28/2023: Policy description updated. Policy statement updated to change "patients" to "individuals" and "Rodnan Scale Scores" to "Rodnan skin scores." Policy Guidelines updated.

12/21/2023: Code Reference section updated to revise the code description for CPT code 96446, effective 01/01/2024.

02/26/2024: Policy description and Policy Guidelines updated with minor changes. Policy statements unchanged.

04/07/2025: Policy description updated with minor changes. Policy statements unchanged.

SOURCE(S)

Blue Cross Blue Shield Association policy # 8.01.25

CODE REFERENCE

This 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.

Medically Necessary Codes

Investigational Codes 

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