Latest Review Date: January 2024

Category:  Surgery                                                                

POLICY:

Embryonal Tumors of the Central Nervous System

Autologous Hematopoietic Cell Transplantation

Autologous hematopoietic cell transplantation may be considered medically necessary as consolidation therapy for previously untreated embryonal tumors of the central nervous system (CNS) that show partial or complete response to induction chemotherapy, or stable disease after induction therapy.

Autologous hematopoietic cell transplantation may be considered medically necessary to treat recurrent embryonal tumors of the CNS.

Tandem autologous hematopoietic cell transplant is considered investigational to treat embryonal tumors of the CNS.

Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation is considered investigational to treat embryonal tumors of the CNS.

Ependymoma

Autologous, tandem autologous, and allogeneic hematopoietic cell transplants are considered investigational to treat ependymoma.

POLICY GUIDELINES:

Other CNS Tumors

Other CNS tumors include astrocytoma, oligodendroglioma, and glioblastoma multiforme. These tumors arise from glial cells, not neuroepithelial cells. These tumors are considered in Medical Policy #372 – Autologous Hematopoietic Cell Transplantation for Malignant Astrocytomas and Glioma.

Due to their neuroepithelial origin, peripheral neuroblastoma and Ewing’s sarcoma may be considered PNETs. These peripheral tumors are considered in Medical Policy #403 – Hematopoietic Cell Transplantation for Solid Tumors of Childhood.

 

DESCRIPTION OF PROCEDURE OR SERVICE:

High-dose chemotherapy with hematopoietic cell transplantation (HCT) has been investigated as a possible therapy in pediatric patients with brain tumors, particularly in those with high-risk disease. The use of HCT has allowed for a reduction in the dose of radiation needed to treat both average- and high-risk disease with a goal of preserving the quality of life and intellectual functioning.

Central Nervous System Embryonal Tumors

Classification of brain tumors is based on both histopathologic characteristics of the tumor and location in the brain. Central nervous system (CNS) embryonal tumors are more common in children and are the most common brain tumor in childhood. Medulloblastomas account for 20% of all childhood CNS tumors. The other types of embryonal tumors are rare by comparison.

Recurrent childhood CNS embryonal tumors are not uncommon, and depending on which type of treatment the patient initially received, autologous HCT may be an option. For patients who receive high-dose chemotherapy and autologous HCT for recurrent embryonal tumors, objective response is 50%–75%; however, long-term disease control is obtained in fewer than 30% of patients, and is seen primarily in patients with a first relapse of localized disease at the time of relapse.

Ependymoma

Ependymoma is a neuroepithelial tumor that arises from the ependymal lining cell of the ventricles and is, therefore, usually contiguous with the ventricular system. An ependymoma tumor typically arises intracranially in children, while in adults a spinal cord location is more common. Ependymomas have access to the cerebrospinal fluid and may spread throughout the entire neuroaxis. Ependymomas are distinct from ependymoblastomas due to their more mature histologic differentiation.

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. The use of cord blood is discussed in Medical Policy #439: Placental/Umbilical Cord Blood as a Source of Stem Cells.

Immunologic compatibility between infused hematopoietic 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 six. 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 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 effect mediated by non-self-immunologic effector cells. While the slower graft-versus-malignancy effect is considered 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. Subsequent to graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and graft-versus-host disease, 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 re-population of the bone marrow with presumably 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 also susceptible to chemotherapy-related toxicities and opportunistic infections before engraftment, but not GVHD.

Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation

Reduced-intensity conditioning 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 in the period during which the beneficial graft-versus-malignancy 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. In this review, the term reduced-intensity conditioning will refer to all conditioning regimens intended to be non-myeloablative.

Autologous HCT allows for the escalation of chemotherapy doses above those limited by myeloablation and has been tried in patients with high-risk brain tumors in an attempt to eradicate residual tumor cells and improve cure rates. The use of allo-HCT for solid tumors does not rely on the escalation of chemotherapy intensity and tumor reduction but rather on a graft-versus-tumor effect. Allo-HCT is not commonly used in solid tumors and may be used if an autologous source cannot be cleared of a tumor or cannot be harvested.

KEY POINTS:

The most recent literature review was performed through December 4, 2023.

Summary of Evidence

For individuals who have newly diagnosed central nervous system (CNS) embryonal tumors who receive autologous hematopoietic cell transplantation (HCT), the evidence includes prospective and retrospective studies. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. For pediatric CNS embryonal tumors, an important consideration is whether the use of HCT may allow for a reduction in radiation dose. Data from single-arm studies using high-dose chemotherapy (HDC) with autologous HCT to treat newly diagnosed CNS embryonal tumors have shown comparable or improved survival (both event-free survival and overall survival) compared with historical controls treated with conventional therapy, with or without radiotherapy, particularly in patients with disease considered high risk. In a retrospective comparative study, survival in patients receiving HDC with HCT and delayed craniospinal irradiation was comparable to survival in those receiving upfront craniospinal irradiation. Overall, data from these observational studies has suggested HCT may allow reduced doses of craniospinal irradiation without worsening survival outcomes. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have recurrent/relapsed CNS embryonal tumors who receive autologous HCT, the evidence includes prospective and retrospective single-arm studies and a systematic review of these studies. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. For recurrent/relapsed CNS embryonal tumors, survival outcomes after HCT are variable, and survival is generally very poor for tumors other than medulloblastoma. Data from some single-arm studies using autologous HCT to treat recurrent CNS embryonal tumors have shown comparable or improved survival compared with historical controls treated with conventional therapy for certain patients. The results of a 2012 systematic review of observational studies in patients with relapsed supratentorial primitive neuroectodermal tumor (sPNET) suggested that a subgroup of infants with chemosensitive disease might benefit from autologous HCT, achieving survival without the use of radiotherapy, whereas outcomes in older children and/or in pineal location are poor with this modality. However, a relatively large prospective multicenter study has reported that HCT was not associated with improved survival outcomes in patients who had a good response to therapy. Overall, data from these single-arm studies has suggested HCT may be associated with improved survival outcomes in select patients, although data for some tumor types is limited (e.g., atypical teratoid/rhabdoid tumors). The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have CNS embryonal tumors who receive tandem autologous HCT, the evidence includes prospective and retrospective single-arm studies. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. Less evidence specifically addresses the use of tandem autologous HCT for CNS embryonal tumors. The available single-arm studies are very small, but appear to report overall survival and event-free survival rates comparable to single autologous HCT. Tandem transplants may allow reduced doses of craniospinal irradiation, with the goal of avoiding long-term radiation damage. However, most studies used standard-dose irradiation, making the relative benefit of tandem autologous HCT uncertain. The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes.

For individuals who have CNS embryonal tumors who receive allogeneic HCT, the evidence includes case reports. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. The available evidence is limited. The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes.

For individuals who have ependymoma who receive autologous HCT, the evidence includes relatively small case series. Relevant outcomes are overall survival, disease-specific survival, and treatment-related morbidity and mortality. The available case series do not report higher survival rates for patients with ependymoma treated with HCT compared with standard therapies. The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

Current National Comprehensive Cancer Network (v.1.2023) guidelines on treating central nervous system (CNS) tumors make the following recommendations about hematopoietic cell transplant (HCT):

• For medulloblastoma and supratentorial primitive neuroectodermal tumor, high-dose chemotherapy with autologous HCT  for localized recurrent disease with maximum safe resection is a category 2A recommendation (based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate).

American Society for Blood and Marrow Transplantation

In 2015, the American Society for Blood and Marrow Transplantation published consensus guidelines on the use of HCT to treat specific conditions, in both clinical trial and clinical practice settings. These guidelines were updated in 2020. Neither the 2015 nor the 2020 guidelines address HCT in treatment of ependymomas. The tumors addressed in this review for which the Society has provided recommendations are listed in Table 1.

Table 1. Recommendations for Use of Autologous and Allogeneic Hematopoietic Cell Transplantation in Pediatric patients (<18 years)

Condition	Treatment Option	2015 Recommendation	2020 Recommendation
Neuroblastoma, high-risk or relapse	Allogeneic HCT	Developmental	Developmental
	Autologous HCT	Standard of care	Standard of care; tandem autologous HCT recommended over single transplant
Medulloblastoma, high-risk	Allogeneic HCT	Not generally recommended	Not generally recommended
	Autologous HCT	Standard of care, clinical evidence available	Standard of care, clinical evidence available
Other malignant brain tumors	Allogeneic HCT	Not generally recommended	Not generally recommended
	Autologous HCT	Standard of care, clinical evidence available	Standard of care, clinical evidence available

HCT: hematopoietic cell transplantation

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Ependymoma, High-Dose Chemotherapy, Autologous Stem Support, Medulloblastoma, Neuroblastoma, Central, Pineoblastoma, Primitive Neuroectodermal Tumors, PNET, Hematopoietic Cell Transplantation, HCT, Embryonal Tumors, Allogeneic HCT

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 Code of Federal Regulation (CFR) 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:

38204	Management of recipient hematopoietic cell donor search and cell acquisition
38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, allogeneic
38206	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
38208	Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing; per donor
38209	;thawing of previously frozen harvest, with washing; per donor
38210	;specific cell depletion with harvest, T cell depletion
38211	;tumor cell depletion
38212	;red blood cell removal
38213	;platelet depletion
38214	;plasma (volume) depletion
38215	;cell concentration in plasma, mononuclear, or buffy coat layer
38220	Diagnostic bone marrow; aspiration(s)
38221	Diagnostic bone marrow; biopsy(ies)
38222	Diagnostic bone marrow; biopsy(ies) and aspiration(s)
38230	Bone marrow harvesting for transplantation; allogeneic
38232	Bone marrow harvesting for transplantation ;autologous
38240	Bone marrow or blood-derived peripheral stem-cell transplantation; allogeneic
38241	Bone marrow or blood-derived peripheral stem-cell transplantation; autologous

                    

HCPCS:

S2150

Bone marrow or blood-derived peripheral stem-cell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical surgical, diagnostic and emergency services)

                       

REFERENCES:

1. Alsultan A, Alharbi M, Al-Dandan S, et al. High-dose chemotherapy with autologous stem cell rescue in Saudi children less than 3 years of age with embryonal brain tumors. J Pediatr Hematol Oncol. Apr 2015; 37(3):204-208. 
2. Bergthold G, El Kababri M, Varlet P, et al. High-dose busulfan-thiotepa with autologous stem cell transplantation followed by posterior fossa irradiation in young children with classical or incompletely resected medulloblastoma. Pediatr Blood Cancer. May 2014; 61(5): 907-12.
3. Bode U, Zimmermann M, Moser O, et al. Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial. J Neurooncol. Dec 2014; 120(3):635-642.
4. Chintagumpala M, Hassall T, Palmer S, et al. A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET. Neuro Oncol. Sep 2009; 11(1):33-40.
5. Dhall G, Grodman H, Ji L, et al. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr Blood Cancer 2008; 50(6): 1169-1175.
6. Dufour C, Foulon S, Geoffray A, et al. Prognostic relevance of clinical and molecular risk factors in children with high-risk medulloblastoma treated in the phase II trial PNET HR+5. Neuro Oncol. Jul 01 2021; 23(7): 1163-1172.  
7. Dufour C, Kieffer V, Varlet P, et al. Tandem high-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk medulloblastoma or supratentorial primitive neuro-ectodermic tumors. Pediatr Blood Cancer. Aug 2014; 61(8):1398-1402.
8. Dunkel IJ, Gardner S, Garvin J et al. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro Oncol. Mar 2010; 12(3):297-303.
9. Dunkel IJ, Boyett JM, Yates A, et al.  High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma.  Children’s Cancer Group.  J Clin Oncol. Jan 1998; 16(1): 222-228.
10. Egan G, Cervone KA, Philips PC, et al. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease. Bone Marrow Transplant. Apr 2016; 51(4):542-545.
11. Fangusaro J, Finlay J, Sposto R, et al. Intensive chemotherapy followed by consolidative myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) in young children with newly diagnosed supratentorial primitive neuroectodermal tumors (sPNETs): Report of the Head Start I and II experience. Pediatr Blood Cancer. Feb 2008; 50(2): 312-318.
12. Friedrich C, von Bueren AO, von Hoff K et al. Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy. Neuro Oncol. Feb 2013; 15(2):224-234.
13. Gajjar A, Chintagumpala M, Ashley D, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): Long-term results from a prospective, multicentre trial. Lancet Oncol 2006; 7(10): 813-820.
14. Geyer JR, Sposto R, Jennings M, et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol. Oct 20 2005; 23(30): 7621-31.
15. Gill P, Litzow M, Buckner J, et al. High-dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system. Cancer. Apr 15 2008; 112(8): 1805-1811.
16. Grill J, Kalifa C, Doz F, et al. A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation in childhood recurrent ependymoma. A phase-II study. Pediatr Neurosurg. Jul 1996; 25(1): 7-12.
17. Grodman H, Wolfe L and Kretschmar C. Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose-intensive chemotherapy followed by autologous hematopoietic stem cell rescue. Pediatr Blood Cancer. Jul 2009; 53(1): 33-36. 
18. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
19. Kanate AS, Majhail NS, Savani BN, et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. Jul 2020; 26(7): 1247- 1256.
20. Kim H, Kang HJ, Lee JW, et al. Irinotecan, vincristine, cisplatin, cyclophosphamide, and etoposide for refractory or relapsed medulloblastoma/PNET in pediatric patients. Childs Nerv Syst. Oct 2013; 29(10):1851-1858.
21. Kostaras X, Easaw JC. Management of recurrent medulloblastoma in adult patients: a systematic review and recommendations. J Neurooncol. Oct 2013; 115(1):1-8.
22. Lee JY, Kim IK, Phi JH et al. Atypical teratoid/rhabdoid tumors: the need for more active therapeutic measures in younger patients. J Neurooncol  April 2012; 107(2):413-419.
23. Lester RA, Brown LC, Eckel LJ, et al. Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor. J Neurooncol. Nov 2014; 120(2):371-379.
24. Lundberg JH, Weissman DE, Beatty PA et al. Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy and allogeneic bone marrow transplantation. J NeuroOncol. Jun 1992; 13(2): 151-155.
25. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. Nov 2015; 21(11):1863-1869.
26. Mason WP, Goldman S, Yates AJ, et al. Survival following intensive chemotherapy with bone marrow reconstitution for children with recurrent intracranial ependymoma: a report of the Children’s Cancer Group. J NeuroOncol April 1998; 37(2): 135-143.
27. Massimino M, Gandola L, Biassoni V, et al. Evolving of therapeutic strategies for CNS-PNET. Pediatr Blood Cancer. Dec 2013; 60(12):2031-2035.
28. Matsuda Y, Hara J, Osugi Y et al. Allogeneic peripheral stem cell transplantation using positively selected CD34+ cells from HLA-mismatched donors. Bone Marrow Transplant. Feb 1998; 21(4): 355-360.
29. Mueller S and Chang S. Pediatric brain tumors: current treatment strategies and future therapeutic approaches. Neurotherapeutics. Jul 2009; 6(3): 570-586.
30. National Cancer Institute Physician Data Query (PDQ). Childhood Meduloblastoma and Other Central Nervous System Embryonal Tumors Treatment. Updated August 16, 2023. www.cancer.gov/cancertopics/pdq/treatment/childCNSembryonal/healthprofessional. 
31. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: central nervous system cancers. Version 1.2023. www.nccn.org/professionals/physician_gls/PDF/cns.pdf. 
32. Odagiri K, Omura M, Hata M, et al. Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors. Radiat Oncol. Sep 11 2014; 9:201.
33. Park ES, Sung KW, Baek HJ et al. Tandem high-dose chemotherapy and autologous stem cell transplantation in young children with atypical teratoid/rhabdoid tumor of the central nervous system. J Korean Med Sci. Feb 2012; 27(2):135-140.
34. Raghuram CP, Moreno L, Zacharoulis S. Is there a role for high dose chemotherapy with hematopoietic stem cell rescue in patients with relapsed supratentorial PNET? J Neurooncol Feb 2012; 106(3):441-447.
35. Reddy AT, Strother DR, Judkins AR, et al. Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333. J Clin Oncol. Apr 10 2020; 38(11): 1175-1185
36. Secondino S, Pedrazzoli P, Schiavetto I et al. Antitumor effect of allogeneic hematopoietic SCT in metastatic medulloblastoma. Bone Marrow Transplant. Jul 2008; 42(2): 131-133.
37. Sung KW, Lim do H, Lee SH et al. Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age. J Neurooncol. Apr 2012; 107(2):335-342.
38. Sung KW, Lim DH, Yi ES, et al. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor. Cancer Res Treat. Oct 2016; 48(4):1408-1419.
39. Sung KW, Yoo KH, Cho EJ, et al.  High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor.  Pediatr Blood Cancer. Apr 2007; 48(4): 408-415.
40. Zacharoulis S, Levy A, Chi SN, et al. Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer. Jul 2007; 49(1): 34-40.
41. Zhang M, Liu C, Zhou H, et al. Meta of classical chemotherapy compared with high-dose chemotherapy and autologous stem cell rescue in newly diagnosed medulloblastoma after radiotherapy. Medicine (Baltimore). Jul 29 2022; 101(30): e29372.

POLICY HISTORY:

Medical Policy Group, January 2010 (2)

Medical Policy Administration Committee, January 2010

Available for comment January 26-March 11, 2010

Medical Policy Group, December 2011 (3); 2012 Code updates – verbiage chg to codes 38208, 38209, and 38230 & new code 38232

Medical Policy Group, February 2012 (2): Updated Key Points & References

Medical Policy Panel, November 2012

Medical Policy Group, January 2013 (2): Updates to Key Points & References

Medical Policy Panel, November 2013

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

Medical Policy Panel, November 2014

Medical Policy Group, November 2014(3): Updates to Key Points, Key Words and References. No change in policy statement.

Medical Policy Panel, January 2016

Medical Policy Group, February 2016 (2): Updates to Key Points, Approved Governing Bodies, and References. Created “previous coding” section for deleted codes G0265-G0267. No change to policy statement.

Medical Policy Panel, January 2017

Medical Policy Group, February 2017 (7): 2017 Updates to Title, Key Points, and References. Previous coding section deleted- G0265-G0267. Removed “stem” from policy statement. No change in intent.

Medical Policy Group, December 2017. Annual Coding Update 2018: Added new CPT code 38222 effective 1/1/18 to the Current Coding section; updated verbiage for revised CPT codes 38220 and 38221.

Medical Policy Panel, January 2018

Medical Policy Group, February 2018 (7): Updates to Description, Key Points, and References. No change to policy statements.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): 2019 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, January 2020

Medical Policy Group, March 2020 (3): 2020 Updates to Key Points and Description, Key Points, Practice Guidelines and Position Statements and References. Added Policy Guidelines section. No changes to policy statement or intent.

Medical Policy Panel, January 2021

Medical Policy Group, January 2021 (3): Updates to Description, Key Points, Practice Guidelines and References.

Medical Policy Panel, January 2022

Medical Policy Group, February 2022 (3): 2022 Updates to Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, January 2023

Medical Policy Group, January 2023 (3): 2023 Updates to Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.         

Medical Policy Panel, January 2024

Medical Policy Group, January 2024 (3): Updates to Description, Key Points, Benefit Application and References. No changes to policy statement or intent.                                                                                                                                                                     

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.