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. Hematopoietic stem cells may be obtained from the transplant recipient (i.e., autologous stem cell transplantation) or from a donor (i.e., allogeneic stem cell transplantation). They may be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates.
High-dose chemotherapy with hematopoietic stem cell transplantation has been investigated as a possible therapy in pediatric brain tumors, particularly those with disease considered high risk. In addition, the use of HSCT has allowed for a reduction in the dose of radiation needed to treat both average- and high-risk disease, with preservation of quality of life and intellectual functioning, without compromising survival.
CNS Embryonal Tumors
Classification of brain tumors is based on both histopathologic characteristics of the tumor and location in the brain. Central nervous system embryonal tumors are more common in children and are the most common brain tumor in childhood. They are primarily composed of undifferentiated round cells, with divergent patterns of differentiation. It has been proposed that these tumors be merged under the term “primitive neuroectodermal tumor” (PNET); however, histologically similar tumors in different locations in the brain demonstrate different molecular genetic alterations.
Embryonal tumors of the central nervous system (CNS) include medulloblastoma, medulloepithelioma, supratentorial PNETs (pineoblastoma, cerebral neuroblastoma, ganglioneuroblastoma), ependymoblastoma, and atypical teratoid/rhabdoid tumor). Medulloblastomas account for 20% of all childhood CNS tumors. The other types of embryonal tumors are rare by comparison. Surgical resection is the mainstay of therapy with the goal being gross total resection with adjuvant radiation therapy, as medulloblastomas are very radiosensitive. In general, use of autologous hematopoietic cell transplantation in individuals with medulloblastoma who have not received radiation treatment has shown no survival benefit for those individuals considered to be at average risk (i.e., individual age greater than 3 years, without metastatic disease, and with total or near total surgical resection [less than 1.5cm2 residual tumor]).
An ependymoma is a neuroepithelial tumor that arises from the ependymal lining cell of the ventricles and is, therefore, usually contiguous with the ventricular system. In children, the tumor typically arises intracranially, while in adults, a spinal cord location is more common. Ependymomas have access to the cerebrospinal fluid and may spread throughout the entire neuroaxis and are distinct from ependymoblastomas due to their more mature histologic differentiation. Initial treatment of ependymoma consists of maximal surgical resection followed by radiotherapy. Chemotherapy usually does not play a role in the initial treatment of ependymoma. However, disease relapse is common, typically occurring at the site of origin. Treatment of recurrence is problematic; further surgical resection or radiation therapy is usually not possible. Given the poor response to conventional-dose chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell transplantation has been investigated as a possible salvage therapy.
Autologous hematopoietic stem cell transplantation for the treatment of embryonal tumors of the central nervous system is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Hematopoietic tandem autologous and allogeneic stem cell transplantation for the treatment of embryonal tumors of the central nervous system is considered investigational.
Hematopoietic stem cell transplantation (i.e. autologous, tandem autologous and allogeneic) for the treatment of an ependymoma tumor is considered investigational.
Autologous hematopoietic stem cell transplantation for the treatment of embryonal tumors of the central nervous system is considered medically appropriate if ANY ONE of the following criteria are met:
New diagnosis when ALL of the following are met:
Treatment is indicated for ANY ONE of the following:
Partial or complete response to induction chemotherapy
Stable disease after induction therapy
ABSENCE of average risk of recurrence in medulloblastoma as indicated by ALL of the following:
Age older than 3 years
No metastatic disease
Total or near total resection [less than 1.5 cm2 residual tumor]
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The evidence to support hematopoietic stem cell transplantation for the treatment of ependymoma includes relatively small case series. The results of these studies do not report higher survival rates for individuals treated with HSCT compared with standard therapies. The evidence is insufficient to determine the effects of the technology on health outcomes.
BlueCross BlueShield Association. Medical Policy Reference Manual. (1:2018). Hematopoietic cell transplantation for central nervous system embryonal tumors and ependymoma (8.01.28). Retrieved August 31, 2018 from BlueWeb. (37 articles and/or guidelines reviewed)
Centers for Medicare & Medicaid Services. CMS.gov. NCD for stem cell transplantation (110.23). Retrieved October 24, 2016 from http://www.cms.gov.
National Cancer Institute. (2017, September).Childhood central nervous system embryonal tumors treatment (PDQ®). Retrieved October 10, 2017 from http://www.cancer.gov.
National Cancer Institute. (2017, September). Childhood ependymoma treatment (PDQ®). Retrieved October 10, 2017 from http://www.cancer.gov.
National Comprehensive Cancer Network. (2018, March). NCCN Guidelines for the Treatment of Cancer (NCCN Guidelines®).Central nervous system cancers (V.1.2018). Retrieved August 31, 2018 from www.nccn.com.
Odagiri, K., Omura, M., Hata, M., Aida, N., Niwa, T., Goto, H., et al. (2014). Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors. Radiation Oncology, 9, 201. (Level 4 evidence)
Raleigh, D., Tomlin, B., Buono, B., Roddy, E., Sear, K., Byer, L., et al. (2017). Survival after chemotherapy and stem cell transplant followed by delayed craniospinal irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients. Journal of Neuro-Oncology, 131 (2), 359-368. Abstract retrieved October 11, 2017 from PubMed database.
Sung, K., Lim, D., Lee, S., Yoo, K., Koo, H., Kim, J., et. al. (2012). Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age. Journal of Neurooncology 107 (2), 335-342. Abstract retrieved October 24, 2016 from PubMed database.
Winifred S. Hayes, Inc. Medical Technology Directory. (2013, December; last update search December 2017). Autologous stem cell transplantation (ASCT) for metastatic primitive neuroectodermal tumor (PNET). Retrieved August 31, 2018 from www.Hayesinc.com/subscribers. (36 articles and/or guidelines reviewed)
MOST RECENT REVIEW DATE: 10/11/2018
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