Hematopoietic Stem-Cell Transplantation for Breast Cancer

POLICY NUMBER

L.8.01.410

DESCRIPTION

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). 

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). 

Conventional Preparative Conditioning for HSCT

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.

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, immune suppressant drugs are required to minimize graft rejection and GVHD, which also increases susceptibility of the patient to opportunistic infections.

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 traditional 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 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 non-myeloablative, as opposed to fully myeloablative (traditional) regimens.

HSCT in Solid Tumors in Adults

HSCT is an established treatment for certain hematologic malignancies; however, its use in solid tumors in adults continues to be largely experimental. Initial enthusiasm for the use of autologous transplant with the use of high-dose chemotherapy and stem cells for solid tumors has waned with the realization that dose intensification often fails to improve survival, even in tumors with a linear-dose response to chemotherapy. With the advent of reduced-intensity 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.

POLICY

No 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.

Single or tandem autologous hematopoietic stem-cell transplantation is considered not medically necessary to treat any stage of breast cancer.

Allogeneic hematopoietic stem-cell transplantation is investigational to treat any stage of breast cancer.

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.

Chemosensitive disease is defined as tumors that respond to standard dose chemotherapy by at least a 50% decrease in size, typically measured by serial computed tomography (CT) scans.

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 # 8.01.27 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 code 38230 added; ICD-9 Procedure 41.01, 41.09 added; HCPCS G0355, G0356, G0357, G0358, G0359, G0360, G0361, G0362, G0363, G0364 added, J9000-J9999 deleted; Non-Covered table - CPT-4 code 38204, 86812, 86813, 86816, 86817, 86821, 86822 added, ICD-9 Procedure 41.02, 41.03 added

3/22/2006: Coding updated. CPT4/HCPCS 2006 revisions added to policy

1/3/2007: Policy reviewed, all medically necessary language removed as newer studies have shown no increase survival of patients with stem cell transplants after high-dose chemotherapy

1/4/2007: Code reference section updated; All CPT, HCPCS, and ICD-9 procedure codes moved to non-covered. Covered codes removed

12/20/2007: Coding updated per 2008 CPT/HCPCS revisions

1/06/2009: Policy reviewed. No changes.

4/20/2010: High Dose Chemotherapy deleted from title. Transplantation added to title. Policy description updated  to include detailed description of Hematopoietic Stem Cell Transplantation (HSCT). Policy statement updated to include Single or Tandem autologous hematopoietic stem-cell transplant is considered not medically necessary to treat any stage of breast cancer. High Dose Chemotherapy language deleted from policy statement section. CPT code reference section update: New CPT codes 86825 and 86826 added to noncovered table. HCPCS codes G0265, G0266 and G0267 deleted from non-covered table due to these codes were deleted codes as of 12-31-2007.

04/19/2011: Policy reviewed; no changes.

03/02/2012: Policy reviewed; no changes.

04/04/2013: Policy reviewed; no changes.

04/01/2014: Policy reviewed; no changes.

03/13/2015: Policy reviewed; description updated to change "radiation therapy" to "radiotherapy." Investigational policy statement updated to change "stem-cell support" to "stem-cell transplantation."

08/26/2015: Code Reference section updated to add ICD-10 codes, updated the code descriptions for 38240, 38241, and 38242; removed deleted code CPT 96445 and replaced with CPT code 96446.

05/27/2016: Policy number A.8.01.27 added.

09/30/2016: Code Reference section updated to add the following new ICD-10 procedure codes: 30230G2, 30233G2, 30240G2, 30243G2, 30230G3, 30233G3, 30240G3, 30243G3, 30230G4, 30233G4, 30240G4, 30243G4, 30230Y2, 30233Y2, 30240Y2, 30243Y2, 30230Y3, 30233Y3, 30240Y3, 30243Y3, 30230Y4, 30233Y4, 30240Y4, and 30243Y4.

12/21/2017: Code Reference section updated to add new 2018 CPT code 38222. Revised descriptions for CPT codes 38220 and 38221 effective 01/01/2108. Removed deleted ICD-10 procedure codes 30230G1, 30233G1, 30240G1, 30243G1, 30230Y1, 30233Y1, 30240Y1, 30243Y1 and ICD-9 procedure codes 41.02, 41.03, 41.05, and 41.08.

09/27/2019: Code Reference section updated to add new ICD-10 procedure codes 30230U2, 30233U2, 30240U2, 30243U2, 30230U3, 30233U3, 30240U3, 30243U3, 30230U4, 30233U4, 30240U4, and 30243U4, effective 10/01/2019. Removed deleted CPT code 86822 and HCPCS code G0364.

10/01/2020: Code Reference section updated to add new ICD-10 procedure codes 30230C0, 30233C0, 30240C0, 30243C0, effective 10/01/2020.

12/27/2021: Code Reference section updated to make note of deleted ICD-10 procedure codes.

11/14/2022: Code Reference section updated to remove deleted ICD-10 procedure codes 30230C0, 30240C0, 30230G0, 30240G0, 30230G2, 30240G2, 30230G3, 30240G3, 30230G4, 30240G4, 30230U2, 30240U2, 30230U3, 30240U3, 30230U4, 30240U4, 30230Y2, 30240Y2, 30230Y3, 30240Y3, 30230Y4, 30240Y4, 30230Y0, and 30240Y0.

04/04/2023: Policy number changed from "A.8.01.27" to "L.8.01.410." Policy reviewed. Policy statements unchanged.

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

04/30/2024: Policy reviewed; no changes.

07/31/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross Blue Shield Association policy # 8.01.27

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Not Medically Necessary/Investigational Codes

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