Stem-Cell Transplant for Astrocytomas and Gliomas
© Blue Cross and Blue Shield of Montana
Current Effective Date:
October 25, 2013
Original Effective Date:
March 05, 2010
October 25, 2013
November 12, 2012; September 27, 2013
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 10 years versus two–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 patients.
Astrocytomas and gliomas arise from the glial cells. Tumors arising from the neuroepithelium constitute a separate category of malignancies that include CNS (central nervous system) neuroblastoma, medulloblastoma, ependymoblastomas, and pineoblastomas. 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.
High-dose chemotherapy (HDC) followed by hematopoietic stem-cell (HSC) (i.e., blood or marrow) transplant is an effective treatment modality for many patients with certain malignancies and non-malignancies. The rationale of this treatment approach is to provide a very dose-intensive treatment in order to eradicate malignant cells followed by rescue with peripheral blood or bone marrow stem-cells.
A 1994 Blue Cross Blue Shield Association Technology Evaluation Center (TEC) Assessment done on use of autologous SCT for astrocytomas and gliomas and other malignancies concluded that evidence available at that time did not demonstrate that this procedure improved health outcomes of adult patients with high-grade glial tumors of the brain.
An initial update of the 1994 TEC Assessment reviewed literature published through 1999 and confirmed the Assessment’s conclusions. It noted that although there was much research interest in use of autologous SCT for glioblastoma multiforme due to its uniformly poor prognosis, the published literature was relatively scant, consisting primarily of single-institution case series.
The following representative examples were cited:
- Bouffet and colleagues reported on a series of 22 children and young adults with high-grade gliomas treated with autologous SCT. The response rate was 29% with one complete and three partial responses. However, the authors concluded that survival with this procedure was no better than that reported with conventional treatments.
- Heideman and colleagues reported on a case series of 13 pediatric patients with bulky disease or recurrent disease treated with SCT plus radiotherapy. While the overall response rate was 31%, the authors similarly concluded that overall survival was no better than conventional treatment regimens.
- Finlay and colleagues reported on a 1996 case series of 45 children and young adults with a variety of recurrent CNS tumors, including gliomas, medulloblastomas, ependymomas, and primitive neuroectodermal tumors. Of the 18 patients with high-grade gliomas, the response rate was 29%. The median survival of this group was 12.7 months. Of the five long-term survivors, all had high-grade glioma with minimal residual disease at the time of transplantation. Based in part on these results, the authors recommended aggressive surgical debulking before this procedure is even considered.
Studies focusing on the use of autologous SCT in adults with glioblastoma multiforme reported results similar to those in children, being most successful in those with minimal disease at the time of treatment, with an occasional long-term survivor.
A review by Brandes and colleagues concluded that the high drug doses used in this treatment caused excessive toxicity that was not balanced by a significant improvement in survival. Similarly, Levin and coworkers concluded that it was unclear whether hematopoietic SCT had a role in management of cerebral gliomas. Additional reports on small, uncontrolled series of patients with pontine gliomas, recurrent oligodendrogliomas, or those undergoing radiation therapies for high-grade gliomas also did not suggest that this treatment improves survival. In a phase II study, Abrey and colleagues evaluated hematopoietic stem-cell transplantation in 39 patients with newly diagnosed oligodendroglioma. The authors reported the median follow-up of surviving patients was 80.5 months and with 78 months progression-free survival. The overall survival median had not been reached and 18 patients (46%) had relapsed.
Additional Review of Literature through 2008
A literature search through July 2008 did not identify any controlled clinical trial publications on hematopoietic SCT for patients with astrocytomas or gliomas.
A search of the National Cancer Institute Physician Data Query (PDQ) Clinical Trials Database, found one ongoing, but not recruiting, phase II/III trial to determine if stem-cell transplant for newly diagnosed high-risk central nervous system tumors (including glioblastoma multiforme and high-grade astrocytoma) increases overall survival. Two other trials have been completed.
The 2008 National Comprehensive Cancer Network (NCCN) Guidelines on Central Nervous System Tumors (v.1.2008) do not list hematopoietic SCT as a treatment option for patients with astrocytomas or gliomas.
Allogeneic, tandem or triple SCT and donor leukocyte infusion for astrocytomas and gliomas is considered experimental, investigational and unproven due to lack of adequate evidence of safety and effectiveness documented in published, peer-reviewed medical literature.
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Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
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- Heideman, R.L., Douglass, E.C., et al. High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas. Journal of Clinical Oncology (1993) 11(8):1458-65.
- HDC/AUSCS for High Grade Glial Tumors of the Brain in Adults. Chicago, Illinois: Blue Cross Blue Shield Association Technology Evaluation Center (TEC) Assessment Program (1994) 9(34):1-10.
- Finlay, J.L., Goldman, S., 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. Journal of Clinical Oncology (1996) 14(9):2495-503.
- Linassier, C., Benboubker, L., 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.
- Fernandez-Hidalgo, O.A., Vanaclocha, V., 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.
- Bouffet, E., Mottolese, C., et al. Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. European Journal of Cancer (1997) 33(1):91-5.
- Jakacki, R.I., Siffert, J., 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. Journal of Neuro-oncology (1999) 44(1):77-83.
- Tandem High Dose Chemotherapy with Thiotepa and Carboplatin Followed by Peripheral Blood Stem Cell Support for Patients with Malignant Brain Tumors. 1999 American Society of Clinical Oncology, NYU Medical Center, NY, NY. Available at www.asco.org .
- Cairncross, G., Swinnen, L., et al. Myeloablative chemotherapy for recurrent aggressive oligodendroglioma. Neuro-oncology (2000) 2(2):114-9.
- Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem Cell Transplant. BCBSA Medical Policy Reference Manual (2005 September) Medicine: 2.03.03.
- Brandes, A.A., Palmisano, V., et al. High-dose chemotherapy with bone marrow rescue for high-grade gliomas in adults. Cancer Investigation (2001) 19(1):41-8.
- Levin, V.A., Leibel, S.A., et al. Neoplasms of the central nervous system. In: Cancer: Principles and Practice of Oncology, ed 6. VT DeVita, Jr, S Hellman, and SA Rosenberg, eds. Philadelphia: Lippincott Williams and Wilkins; (2001) 2100-60.
- Bouffet, E., Raquin, M., 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.
- Abrey, L.E., Childs, B.H., et al. High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up. Neuro Oncology (2006) 8(2):183-8.
- Central Nervous System Cancers. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. V.1.2008. Available at www.nccn.org . (accessed - July 2008).
- Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 August) Therapy 8.01.31.
||Policy updated with literature search through August 2012. Reference 12 added. Policy statement unchanged. |
||Policy formatting and language revised. Policy statement unchanged. Title changed from "Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas".|