Latest Review Date: February 2024

Category: Surgery

POLICY:

Autologous or allogeneic hematopoietic stem cell transplantation (ablative and non-myeloablative) is considered investigational as a treatment of malignant astrocytomas and gliomas. (The latter diagnosis includes both glioblastoma multiforme and oligodendroglioma.)

DESCRIPTION OF PROCEDURE OR SERVICE:

Malignant glial tumors are usually resistant to conventional treatment approaches.  Autologous hematopoietic stem-cell transplantation has been investigated as a treatment for malignant astrocytomas and gliomas.

Hematopoietic 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 individuals who receive bone-marrow-toxic doses of cytotoxic drugs with or without whole-body radiation therapy.  Bone marrow stem cells may be obtained from the transplant recipient (autologous HSCT) can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta 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. The use of cord blood is discussed in Medical Policy #439: Placental/Umbilical Cord Blood as a Source of Stem Cells.

Preparative Conditioning for Hematopoietic Cell Transplantation

Autologous HCT necessitates myeloablative chemotherapy to eradicate cancerous cells from the blood and bone marrow, thus permitting subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic progenitor cells.  Therefore, autologous HSCT is typically performed as consolidation therapy when the individual’s disease is in complete remission.  Individuals who undergo autologous HSCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not graft-versus-host disease.

Astrocytomas and Gliomas

Diffuse fibrillary astrocytomas are the most common type of brain tumor in adults. These tumors are classified histologically into three grades of malignancy: grade II astrocytoma, grade III anaplastic astrocytoma, and grade IV glioblastoma multiform. Oligodendrogliomas are diffuse neoplasms that are clinically and biologically most closely related to diffuse fibrillary astrocytomas. However, these tumors generally have better prognoses than diffuse astrocytomas, with mean survival times of ten years versus two to three years. In addition, oligodendrogliomas appear to be more chemosensitive than other types of astrocytomas. Glioblastoma multiforme is the most malignant stage of astrocytoma, with survival times of less than two years for most individuals.

Treatment of primary brain tumors focuses on surgery, either with curative intent or optimal tumor debulking. Surgery may be followed by radiation therapy and/or chemotherapy. Survival after chemoradiotherapy is largely dependent on the extent of residual tumor after surgical debulking. Therefore, tumors arising in the midline, basal ganglia, or corpus callosum or those arising in the eloquent speech or motor areas of the cortex, which typically cannot be extensively resected, have a particularly poor outcome. Treatment of children younger than three years is complicated by the long-term effects of radiation therapy on physical and intellectual function. Therefore, in young children, CNS radiation is avoided whenever possible.

Note: Astrocytomas and gliomas arise from the glial cells. Tumors arising from the neuroepithelium constitute a separate category of malignancies that include CNS neuroblastoma, medulloblastoma, ependymoblastomas, and pinealoblastoma. Collectively these tumors may be referred to as primitive neuroectodermal tumors (PNETs). Ependymomas also arise from the neuroepithelium but, because of their more mature histologic appearance, are not considered a member of the PNET family.

The use of high-dose chemotherapy in tumors arising from the neuroepithelium is addressed separately in policy #404: Hematopoietic Cell Transplantation for CNS Embryonal Tumors and Ependymoma.

KEY POINTS:

The most recent literature search was performed through March 5, 2024.

Summary of Evidence

The data on the use of autologous hematopoietic cell transplantation for malignant astrocytomas and gliomas, consisting of case series, has, in general, shown no survival benefit compared to conventional therapy with increased treatment-related toxicity. Therefore, this is considered investigational for this indication.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

The 2023 NCCN Guidelines on Central Nervous System Tumors (v2.2023) do not list hematopoietic cell transplantation as a treatment option for patients with astrocytomas or gliomas.

KEY WORDS:

Astrocytoma, High-Dose Chemotherapy, Glioblastoma Multiforme, Astrocytoma, Oligodendroglioma, stem-cell transplant, Hematopoietic Cell Transplantation, HCT, SCT

APPROVED BY GOVERNING BODIES:

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 the Code of Federal Regulation title 21, parts 1270 and 1271.  Hematopoietic stem cells are included in these regulations.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply.  Refer to member’s benefit plan.

CURRENT CODING: 

CPT Codes:

HCPCS Codes:

REFERENCES:

1. Abrey LE, Childs BH, Paleologos N, et al.  High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up.  Neuro Oncol 2006; 8(2):183-8.
2. Blue Cross Blue Shield Association.  Technology Evaluation Center (TEC) Assessment 1994; Tab 34.
3. Bouffet E, Mottolese C, Jouvet A, et al.  Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas.  Eur J Cancer 1997; 33(1):91-5.
4. Bouffet E, Raquin M, Doz F, et al.  Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas.  Cancer 2000; 88(3):685-92.
5. Brandes AA, Palmisano V, Pasetto LM, et al.  High-dose chemotherapy with bone marrow rescue for high-grade gliomas in adults.  Cancer Invest 2001; 19(1):41-8.
6. Cairncross G, Swinnen L, Bayer R, et al.  Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.  Neuro-oncol 2000; 2(2):114-9.
7. Fernandez-Hidalgo OA, Vanaclocha V, Vieitez JM, et al.  High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: Benefit for selected patients.  Bone Marrow Transplant 1996; 18(1):143-9.
8. Finlay JL, Goldman S, Wong MC, et al.  Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors.  The Children’s Cancer Group.  J Clin Oncol 1996; 14(9):2495-503.
9. Heideman RL, Douglass EC, Krance RA, et al.  High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas.  J Clin Oncol 1993; 11(8):1458-65.
10. Jakacki RI, Siffert J, Jamison C et al.  Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas.  J Neurooncol 1999; 44(1):77-83. 
11. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
12. Levin VA, Leibel SA and Gutin PH.  Neoplasms of the central nervous system.  In: Cancer: Principles and Practice of Oncology, 6th edition.  VT DeVita, Jr, S Hellman, and SA Rosenberg, eds. Philadelphia: Lippincott Williams and Wilkins; 2001: 2100-60.
13. Linassier C, Benboubker L, Velut S, et al.  High-dose BCNU with ABMT followed by radiation therapy in the treatment of supratentorial glioblastoma multiforme.  Bone Marrow Transplant 1996; 18(suppl 1): S69-72.
14. National Comprehensive Cancer Network.  Central Nervous System Cancers.  Clinical Practice Guidelines in Oncology, Version 2 2023. www.nccn.org/professionals/physician_gls/pdf/ped_cns.pdf. 
15. Ricard D, Idbaih A, Ducray F et al. Primary brain tumours in adults. Lancet 2012; 379(9830): 1984-96.

POLICY HISTORY:

Medical Policy Group, July 2009 (2)

Medical Policy Administration Committee, August 2009

Available for comment August 10-September 23, 2009

Medical Policy Group, February 2011; Description & HCPCS updated

Medical Policy Panel, September 2011

Medical Policy Group, September 2011 (2) Key Points, References updated

Medical Policy Group, December 2011 (3); Added CPT codes 38230 & 38232 and updated verbiage to 38208 and 38209 for 2012 Code update

Medical Policy Group, October 2012 (2): 2012 Update to Key Points and References

Medical Policy Panel, July 2013

Medical Policy Group, July 2013 (3):  2013 Update to Description and Key Points; no change in policy statement

Medical Policy Group, July 2013 (3): Effective July 22, 2013 this policy will no longer be scheduled for regular literature reviews and updates.

Medical Policy Group, December 2017: Annual Coding Update 2018.  Added new CPT code 38222 effective 01/01/18 to Current Coding.  Updated verbiage for revised codes 38220 and 38221.

Medical Policy Group, August 2019 (3): 2019 Updates to Key Points, Practice Guidelines and Position Statements and References. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy.

Medical Policy Group, March 2021 (3): 2021 Updates to Description, Key Points and Practice Guidelines and Position Statements, and Key Words: added: Hematopoietic Cell Transplantation, HCT. Included allogeneic stem cell transplant in investigational statement since stem cell transplantation is not a recommended treatment for astrocytomas or gliomas. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy. Allogeneic HCT coding added: HCPCS: S2140, S2142, and CPT: 38240.

Medical Policy Group, March 2022 (3): 2022 Updates to Key Points, Practice Guidelines and Position Statements, and References. Reviewed by Consensus. No new information was identified that would alter the coverage statement of this policy.

Medical Policy Group, March 2023 (3): 2023 Updates to Description, Key Points, Practice Guidelines and Position Statements, Benefit Application, Approved By Governing Bodies, and References. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy.

Medical Policy Group, February 2024 (3): 2024 Updates to Description and References. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.