Hematopoietic Cell Transplantation for Selected Childhood Solid Tumors

Coverage Summary

scope_summary: Defines medical necessity and investigational/experimental positions for autologous, tandem, repeat autologous, and allogeneic hematopoietic cell transplantation for select pediatric solid tumors (primarily neuroblastoma, Ewing's sarcoma family, PNET/medulloblastoma, ependymoma, retinoblastoma, Wilms' tumor) and related procedures; lists applicable CPT/HCPCS/ICD-10 codes and background evidence summaries. policy_number: 0496; status: CURRENT; policy effective date: Effective since 2002-02-01; last review: 07/18/2023.

overview: The policy takes a mixed coverage stance: autologous hematopoietic cell transplantation (including repeat and tandem procedures) is considered medically necessary for specified indications in high-risk neuroblastoma and several other pediatric solid tumors when selection criteria are met, while allogeneic transplantation and adoptive cellular immunotherapy from donor sources are generally considered experimental and investigational for multiple listed tumor types.

Policy Quick Facts

Policy TitleHematopoietic Cell Transplantation for Selected Childhood Solid Tumors

PayerAetna

Policy Number0496

StatusCURRENT

Scope SummaryDefines medical necessity and investigational/experimental positions for autologous, tandem, repeat autologous, and allogeneic hematopoietic cell transplantation for select pediatric solid tumors (neuroblastoma, Ewing's sarcoma family, PNET/medulloblastoma, ependymoma, retinoblastoma, Wilms' tumor); lists applicable CPT/HCPCS/ICD-10 codes and background evidence summaries.

Policy Effective DateEffective since 2002-02-01

Last ReviewLast reviewed 2023-07-18

Medical Necessity Criteria

Medical Necessity - Autologous HCT for High-Risk Neuroblastoma

Autologous hematopoietic cell transplantation is medically necessary for members with high-risk neuroblastoma when transplanting institution's protocol selection criteria are met, or in absence of protocol when member lacks concurrent disease that would compromise durable complete remission and ANY of the following selection criteria are met:

ANY of the following

As primary treatment for persons in Stage II to Stage III neuroblastoma when associated with more than 10 copies of the n-myc oncogene.
As primary treatment for persons in Stage IV neuroblastoma.
As therapy for primary recurrent or refractory disease when further treatment with a conventional-dose therapy is unlikely to attain a durable remission.

Definition of High-Risk Neuroblastoma (any one of the following qualifies as high-risk)

Experimental, Investigational, and Not Medically Necessary

Experimental and Investigational (Not Medically Necessary)

The following are considered experimental and investigational because effectiveness has not been established:

ANY of the following

Adoptive cellular immunotherapy from haploidentical or matched donors following hematopoietic stem cell transplantation for childhood solid tumors.
Allogeneic hematopoietic cell transplantation for the treatment of ependymoma.
Allogeneic hematopoietic cell transplantation for the treatment of Ewing's sarcoma family of tumors.
Allogeneic hematopoietic cell transplantation for the treatment of neuroblastoma.

Coding

Covered CPT codes if selection criteria metCPTCovered

38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic [not covered for neuroblastoma]
38206	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
38230	Bone marrow harvesting for transplantation [not covered for neuroblastoma]
38232	Bone marrow harvesting, autologous
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor [not covered for neuroblastoma]
38241	Hematopoietic progenitor cell (HPC); autologous transplantation
38242	Allogeneic lymphocyte infusions
86813	HLA typing; A, B or C multiple antigens
86817	HLA typing; DR/DQ, multiple antigens
86821	Lymphocyte culture, mixed (MCL)

1–10 of 12

1/2

Covered HCPCS codes if selection criteria metHCPCSCovered

S2150

Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; includes pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and pre- and post-transplant care in the global definition.

HCPCS codes not covered for indications listed in the CPBHCPCSNot Covered

M0075	Cellular therapy
S2107	Adoptive immunotherapy i.e., tumor-infiltrating lymphocyte therapy per course of treatment

Other related code rangesmixed

J9000-J9999	Chemotherapy drugs code range
Q0083-Q0085	Chemotherapy administration

ICD-10 codes covered if selection criteria metICD-10Covered

C40.00-C41.9	Malignant neoplasm of bone and articular cartilage [relapsed or progressive Ewing's sarcoma family of tumors covered for autologous transplant - not covered for allogeneic]
C64.1-C64.9	Malignant neoplasm of kidney, except pelvis [Wilms' tumor]
C69.20-C69.22	Malignant neoplasm of retina
C71.0-C71.9	Malignant neoplasm of brain [neuroblastoma - covered for autologous & allogeneic bone marrow or stem cell transplant] [medulloblastoma covered for autologous only - not covered for allogeneic]
C72.0-C72.9	Malignant neoplasm of spinal cord, cranial nerves and other parts of CNS [neuroblastoma - covered for autologous & allogeneic transplant] [medulloblastoma covered for autologous only - not covered for allogeneic] [autologous or allogeneic not covered for ependymoma]
C74.00-C74.92	Malignant neoplasm of adrenal gland [neuroblastoma] [autologous only]
C75.3	Malignant neoplasm of pineal gland

ICD-10 codes not covered for indications listed in the CPB (examples)ICD-10Not Covered

C49.0-C49.9

Malignant neoplasm of other connective and soft tissue [soft tissue sarcomas]

Provider Actions / Prior Authorization & Documentation

Documentation Required

Institutional protocol selection criteria required

Transplant coverage is contingent on meeting the transplanting institution's protocol selection criteria. If the transplanting institution does not have a protocol, autologous hematopoietic cell transplantation may be considered when the member meets the medical necessity criteria in this policy and does not have concurrent disease that would seriously compromise the chance of obtaining a durable complete remission.

Must meet the transplanting institution's protocol selection criteria; if no institutional protocol exists, the member must meet the policy medical necessity criteria and not have concurrent disease that would seriously compromise a durable complete remission.

Prior Authorization

Coverage contingent on medical necessity criteria

Coverage is contingent on medical necessity criteria being met as specified in this policy. Prior authorization may be required and coverage applies only when the selection/medical necessity criteria are satisfied for the specific diagnosis and treatment described.

Background and Evidence Summary

background: Neuroblastoma is the most common extracranial solid tumor of childhood, often arising in the abdomen (adrenal gland or paraspinal ganglion) with metastatic disease present in 50% to 66% at diagnosis; staging follows the International Staging System (I–IV and IVS) and risk is stratified by stage, age, MYCN (n-myc) amplification and histology.

background: Autologous transplant (ABMT/ASCT) re-infuses the patient's previously harvested bone marrow or peripheral blood stem cells after myeloablative high-dose chemotherapy (HDC); allogeneic transplant uses donor stem cells and may provide a graft-versus-tumor effect but carries different risks and has limited established benefit in many pediatric solid tumors.

background: Tandem (sequential) transplants deliver a cycle of HDC with autologous stem cell rescue followed months later by a second HDC/ASCT to attempt improved durable responses. Typical HDC regimens for neuroblastoma use a platinum compound plus an epipodophyllotoxin (etoposide or teniposide) combined variably with melphalan, cyclophosphamide or doxorubicin, often with total body irradiation (TBI) added. Hospital stay for HDC without TBI typically ranges from 2 to 4 weeks with discharge once fever-free for 48 hours, adequate WBC (>500), resolution of mucositis/diarrhea and ability to maintain oral intake; regimens including TBI average a ~30-day hospitalization and require laminar flow room care during cytopenic nadir.

Study/Reference	Key finding(s)
Stram et al (1995)	4-year EFS 40% with HDC group vs 19% with conventional therapy in stage IV patients.
Matthay et al (1994,1998,1999)	3-year EFS 34% in HDC-ABMT arm vs 18% in control; supports autologous transplant benefit in high-risk neuroblastoma.
Grupp et al (2000)	Phase II: tandem HDC with stem cell rescue feasible and may improve disease-free survival.
Perez-Martínez et al (2005)	2-year EFS 37.67% ± 14% overall; 57% ± 15% high-risk group; TRM 15%.
Sung et al (2007)	3-year EFS 83.3% ±15.2 (high-risk >3y), 62.5% ±20.5 (<3y), 29.1% ±15.7 (relapsed); tandem HDC associated with higher EFS in selected groups.
Kadota et al (2008)	19/29 CR or continuous CR; 9/29 long-term survivors; no toxic deaths reported in series.
Cheuk et al (2008)	5-year EFS 53.9% in pediatric brain tumor AHSCT series; one early transplant-related death; long-term survivors mainly had CR before transplant.
Fangusaro et al (2008)	sPNET 5-year EFS 39% (95% CI 24-53); OS 49% (95% CI 33-62); many survivors avoided radiotherapy.
Butturini et al (2009)	3-year post-transplant EFS 83% ±15% (unirradiated) vs 20% ±12% (previously irradiated); higher toxic deaths in previously irradiated group.
Dunkel et al (2010)	Median OS 26.8 months; EFS and OS 24% at 10 years in previously irradiated recurrent medulloblastoma after HDC+ASCR; some long-term survivors but TRM present.
Grill et al (1996)	In refractory/recurrent ependymoma no radiological responses >50%; 3 disease-free survivors; severe toxicity with 1 toxicity-related death.
Mason et al (1998)	High toxicity in recurrent ependymoma series: 5 treatment-related deaths; no partial or complete responses observed.
Raghuram et al (2012)	Systematic review of relapsed sPNET: 12-month OS 44.2% ±7.5; better outcomes in children <36 months and non-pineal locations; pineal location adverse prognostic factor.
Dunkel et al (2010) retinoblastoma series	2 event-free survivors (of 8); one induction toxic death; suggests some benefit in stage 4b retinoblastoma with intensive therapy including HDC-ASCR.
Palma et al (2012)	In 11 metastatic retinoblastoma patients treated with HDC-ASCR, 7 disease-free survivors (median follow-up 39 months); no toxic deaths in series.
Ha et al (2013)	Meta-analysis for relapsed Wilms' tumor: pooled HR for EFS 0.87 (95% CI 0.67-1.12); possible benefit in very high risk HR 0.50 (0.31-0.82).
Presson et al (2010)	ASCR 4-year OS 54.1% (combined studies); better outcomes for lung-only relapses compared with other relapse sites.
Peinemann et al (2017) Cochrane review NRSTS	Single RCT: no survival advantage for HDCT + AHSCT vs standard-dose chemo; 3-year OS 32.7% vs 49.4%.
Faraci et al (2019) SOT after HSCT (EBMT multicenter survey)	44 SOTs after HSCT reported; 1- and 5-year OS after SOT 85.7% and 80.4% respectively across organs.
Adoptive cellular immunotherapy (single-center, n=18)	1.5-year OS 19.5% and PFS 16.1% overall; in CR patients 1.5-year OS 50.1% and PFS 42.7%; high cumulative relapse (79.8% at 1.5 yrs) and acute GVHD in 50% (mostly grade I-II).

Definitions

Primary refractory: Tumor that does not achieve a complete remission after initial standard-dose chemotherapy.

Relapse: Tumor recurrence after a prior complete remission.

High-risk neuroblastoma: Defined by listed stage and MYCN amplification/histology criteria (see policy criteria tree; any one qualifying category constitutes high-risk).

ABMT/ASCT: Autologous bone marrow transplant / autologous stem cell transplant; re-infusion of patient's previously harvested marrow or peripheral blood stem cells after myeloablative therapy.

HDC: High-dose chemotherapy.

ASCR/AHCT/AHSCT: Autologous stem cell rescue / autologous hematopoietic cell transplantation.

TRM: Treatment-related mortality.

sPNET: Supratentorial primitive neuroectodermal tumor.

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