Hematopoietic Cell Transplantation for Miscellaneous Solid Tumors in Adults

POLICY NUMBER

A.8.01.24

DESCRIPTION

Hematopoietic cell transplantation (HCT) 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 HCT (allo-HCT) for a graft-versus-tumor effect of donor-derived T cells in metastatic solid tumors.

Though cancer incidence along with overall mortality has been declining in the United States, certain population groups continue to have an increased risk of cancer progression and mortality due to social, economic, and environmental disadvantages. The National Cancer Institute has published statistics on cancer disparities in relation to various criteria including specific racial and ethnic groups, gender, and geography. Some key incidence and mortality statistics in the United States are as follows: incidence rates of lung, colorectal, and cervical cancers are increased in rural Appalachia compared to urban areas; American Indians/Alaska Natives have increased mortality rates from kidney, liver, and intrahepatic bile duct cancer compared to other racial and ethnic groups; Black men are twice as likely to die of prostate cancer than White men.

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 infusedhematopoietic 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. 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 the 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 to be 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. After graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and GVHD, 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 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 susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not GVHD.

Reduced-Intensity Conditioning for Allo-HCT

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 reduced-intensity conditioning 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 reduced-intensity conditioning is to reduce disease burden and to minimize associated treatment-related morbidity and non-relapse mortality (NRM) 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 reduced-intensity conditioning with allo-HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most will subsequently convert to full-donor chimerism. For this policy, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be nonmyeloablative.

HCT in Solid Tumors in Adults

HCT 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.

HCT as a treatment for ovarian cancer, germ cell tumors, ependymoma, or malignant glioma is addressed in separate policies,  Hematopoietic Cell Transplantation for Epithelial Ovarian Cancer , Hematopoietic Cell Transplantation in the Treatment of Germ Cell Tumors , and Hematopoietic Cell Transplantation for CNS Embryonal Tumors and Ependymoma , respectively. HCT as a treatment for breast cancer is not addressed. This policy collectively addresses other solid tumors of adults for which HCT 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, 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 unless the Member receives prior authorization through Case Management from Blue Cross & Blue Shield of Mississippi.

Autologous or allogeneic hematopoietic cell transplantation is considered investigational for the following malignancies in adults:

• Lung cancer, any histology

• Colon cancer

• Rectal cancer

• Pancreatic cancer

• Stomach cancer

• Esophageal cancer

• Gall bladder cancer

• Cancer of the bile duct

• Renal cell cancer

• Cervical cancer

• Uterine cancer

• Cancer of the fallopian tubes

• Prostate cancer

• Nasopharyngeal cancer

• Paranasal sinus cancer

• Neuroendocrine tumors

• Soft tissue sarcomas

• Thyroid tumors

• Tumors of the thymus

• Tumors of unknown primary origin

• Malignant melanoma. 

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.

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 # 8.01.24 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 chemotherapy" 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 A.8.01.24 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.

01/31/2017: Policy updated to change "hematopoietic stem-cell transplantation" to "hematopoietic cell transplantation." Policy description updated. Policy statement unchanged.

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

02/13/2018: Policy reviewed; no changes.

03/13/2019: Policy reviewed. Policy statement unchanged. State and School Employee members added to Policy Exceptions. Code Reference section updated to remove deleted CPT code 86822 and HCPCS code G0364.

09/24/2019: 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.

02/21/2020: Policy description updated. Policy statement unchanged.

03/05/2021: Policy reviewed; no changes.

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

02/17/2022: Policy reviewed. Policy statement updated to change "transplant" to "transplantation" and to add "in adults."

02/28/2023: Policy description updated regarding cancer disparities. Policy statement unchanged. Code Reference section updated to remove deleted ICD-10 procedure codes 30230G0, 30230Y0, 30240G0, 30240Y0, 30230G2, 30240G2, 30230G3, 30240G3, 30230G4, 30240G4, 30230U2, 30240U2, 30230U3, 30240U3, 30230U4, 30240U4, 30230Y2, 30240Y2, 30230Y3, 30240Y3, 30230Y4, and 30240Y4.

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 updated with minor changes. Policy statement unchanged.

04/07/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross Blue Shield Association policy # 8.01.24

CODE REFERENCE

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

Investigational Codes

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