MEDICAL POLICY

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DESCRIPTION
SCOPE
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RATIONALE
REFERENCES
CODING
APPENDIX
HISTORY

Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas

Number 8.01.31

Effective Date September 27, 2013

Revision Date(s) 09/09/13; 12/11/12; 10/11/11; 12/14/2010; 09/15/09; 12/16/08; 11/13/07; 09/12/06; 10/11/05; 09/14/04; 08/12/03; 06/17/03; 02/01/00

Replaces N/A

Policy

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

Related Policies

7.01.50

Placental and Umbilical Cord Blood as a Source of Stem Cells

8.01.17

Hematopoietic Stem-Cell Transplantation for Multiple Myeloma

8.01.20

Hematopoietic Stem-Cell Transplantation for Non-Hodgkin Lymphomas

8.01.21

Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndromes and Myeloproliferative Neoplasms

8.01.22

Allogeneic Hematopoietic Stem-Cell Transplantation for Genetic Diseases and Acquired Anemias

8.01.23

Hematopoietic Stem-Cell Transplantation for Epithelial Ovarian Cancer

8.01.24

Hematopoietic Stem-Cell Transplantation for Miscellaneous Solid Tumors in Adults

8.01.25

Hematopoietic Stem-Cell Transplantation for Autoimmune Diseases

8.01.26

Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia

8.01.27

Hematopoietic Stem-Cell Transplantation for Breast Cancer

8.01.28

Hematopoietic Stem-Cell Transplantation for CNS Embryonal Tumors and Ependymoma

8.01.29

Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma

8.01.30

Hematopoietic Stem-Cell Transplantation for Treatment of Chronic Myelogenous Leukemia

8.01.35

Hematopoietic Stem-Cell Transplantation in the Treatment of Germ Cell Tumors

8.01.42

Hematopoietic Stem-Cell Transplantation for Primary Amyloidosis

8.01.54

Hematopoietic Stem-Cell Transplantation for Waldenstrom Macroglobulinemia

8.01.511

Hematopoietic Stem-Cell Transplantation for Solid Tumors of Childhood

8.01.514

Hematopoietic Stem-Cell Support for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

8.01.520

Hematopoietic Stem-Cell Transplantation for Acute Lymphoblastic Leukemia

Policy Guidelines

N/A

Description

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.

Background

Hematopoietic Stem-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 patients 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) and 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. Cord blood is discussed in greater detail in policy No. 7.01.50.

Preparative Conditioning for Hematopoietic Stem-Cell Transplantation

Autologous HSCT 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. As a consequence, autologous HSCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients 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 3 grades of malignancy: grade II astrocytoma, grade III anaplastic astrocytoma, and grade IV glioblastoma multiforme. 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 23 years, respectively. 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 2 years for most patients.

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 3 years is complicated by the long-term effects of radiation therapy on physical and intellectual function. Therefore, in young children, radiation of the central nervous system (CNS) 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 pinealoblastomas. 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 No. 8.01.28 (See Related Policies).

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application

N/A

Rationale

An updated literature search through June 7, 2013 identified no controlled studies that would change the conclusions of this policy. The published literature consists primarily of single-institution case series. Bouffet and colleagues reported on a series of 22 children and young adults with high-grade gliomas treated with autologous hematopoietic stem-cell transplantation (HSCT). (1) The response rate was 29% with 1 complete and 3 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 HSCT plus radiotherapy. (2) 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 central nervous system (CNS) tumors, including gliomas, medulloblastomas, ependymomas, and primitive neuroectodermal tumors. (3) 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 5 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 HSCT 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. (4,5)

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. (6) Additional reports on small, uncontrolled series of patients with pontine gliomas, (7) recurrent oligodendrogliomas, (8) or those undergoing radiation therapy for high-grade gliomas (9) 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. (10) The authors reported the median follow-up of surviving patients was 80.5 months, with 78 months progression-free survival. The overall survival median had not been reached, and 18 patients (46%) had relapsed.

A nonrandomized study compared survival outcomes of 27 children (age, 0.422 years) with recurrent malignant astrocytomas who underwent myeloablative chemotherapy and autologous HSCT with outcomes in a matched historical cohort (n=56) that received standard chemotherapy regimens following tumor recurrence.(11) Among the 27 children who received myeloablative chemotherapy and autologous HSCT, 5 (18%) succumbed to treatment-related toxicities within approximately 2 months of transplantation, 17 (63%) had disease progression, while 5 survived and were alive a median of 11 years (range: 813 years) after transplantation. Overall survival rates at 4 years were 40 ± 14% for transplant patients versus 7 ± 4% with conventional chemotherapy (p=0.018, hazard ratio [HR]:1.9; 95% confidence interval [CI]: 1.1–3.2). The results of this study suggest myeloablative chemotherapy with autologous HSCT can produce long-term survival among children with recurrent malignant astrocytoma. However, lack of a contemporaneous treatment comparison group precludes conclusions as to the relative efficacy of this approach.

A comprehensive review article identified in the search did not report any evidence for the role of HSCT in this disease. (12)

Summary

The data on the use of autologous hematopoietic stem-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.

National Cancer Institute Physician Data Query (PDQ®) Clinical Trials Database

A search in June 2013 found one active U.S. Phase II trial of hematopoietic stem-cell transplantation for newly diagnosed central nervous system tumors, including glioblastoma multiforme and gliosarcoma (NCT00669669). This study is currently recruiting participants (N=24) with the estimated completion date of February 2017.

National Comprehensive Cancer Network (NCCN) Guidelines

The 2013 NCCN Guidelines on Central Nervous System Tumors (v.2.2013) do not list hematopoietic stem -cell transplantation as a treatment option for patients with astrocytomas or gliomas. (Available online at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf)

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Cairncross G, Swinnen L, Bayer R et al. Myeloablative chemotherapy for recurrent aggressive oligodendroglioma. Neurooncol 2000; 2(2):114-9.
  9. 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.
  10. 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. Neurooncol 2006;8(2):183-8.
  11. Finlay JL, Dhall G, Boyett JM et al. Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma: outcome compared with conventional chemotherapy: a report from the Children's Oncology Group. Pediatr Blood Cancer 2008; 51(6):806-11.
  12. Ricard D, Idbaih A, Ducray F et al. Primary brain tumours in adults. Lancet 2012; 379(9830):1984-96.National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology. Central Nervous System Cancers. V.2.2013. Last accessed August 2013.
  13. Reviewed and recommended for adoption by the Company Oncology Advisory Panel, February 22, 2007, February 19, 2009; November 18, 2010, November 15, 2012.

Coding

Codes

Number

Description

CPT

38206

Blood derived hematopoietic progenitor cell harvesting for transplantation, per collection, autologous

 

38207

Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage

 

38208

Transplant preparation of hematopoietic progenitor cells; Thawing of previously frozen harvest, without washing

 

38209

Thawing of previously frozen harvest with washing

 

38210

Specific cell depletion within 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

 

38232

Bone marrow harvesting for transplantation; autologous

 

38241

Bone marrow or blood-derived peripheral stem cell transplantation; autologous

 

86825

Human leukocyte antigen (HLA) crossmatch, non-cytotoxic (e.g., using flow cytometry); first serum sample or dilution

 

86826

Human leukocyte antigen (HLA) crossmatch, non-cytotoxic (e.g., using flow cytometry); each additional serum sample or sample dilution (List separately in addition to primary procedure)

ICD-9 Procedure

41.00

Bone marrow transplant, not otherwise specified

 

41.01

Autologous bone marrow transplant, without purging

 

41.04

Autologous hematopoietic stem cell transplant without purging

 

41.07

Autologous hematopoietic stem cell transplant with purging

 

41.09

Autologous bone marrow transplant with purging

 

41.91

Aspiration of bone marrow from donor for transplant

 

99.79

Other therapeutic apheresis (includes harvest of stem cells)

ICD-9 Diagnosis

191.0

Malignant neoplasm of the cerebrum, except lobes and ventricles

 

191.1

Frontal lobe

 

191.2

Temporal lobe

 

191.3

Parietal lobe

 

191.4

Occipital lobe

 

191.5

Ventricles

 

191.6

Cerebellum NOS

 

191.7

Brain stem

 

191.8

Other parts of brain

 

191.9

Brain, unspecified

ICD-10-CM
(effective 10/01/14)

C71.0-C71.9

Malignant neoplasm of brain code range

ICD-10-PCS
(effective 10/01/14)

30243G0, 30243X0, 30243Y0

Percutaneous transfusion, central vein, bone marrow or stem cells, autologous, code list

 

07DQ0ZZ, 07DQ3ZZ, 07DR0ZZ, 07DR3ZZ, 07DS0ZZ, 07DS3ZZ

Surgical, lymphatic and hemic systems, extraction, bone marrow, code list

HCPCS

S2150

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

Type of Service

Therapy

 

Place of Service

Inpatient
Outpatient

 

Appendix

N/A

History

Date

Reason

02/01/00

Add to Therapy Section - New Policy — replaces BC.8.01.15, original master policy on high-dose chemotherapy for miscellaneous malignancies. However, policy statement is unchanged.

06/17/03

Replace policy - Update CPT codes only.

08/12/03

Replace policy - Reviewed and recommended for adoption without any changes by Company Oncology Advisory Panel July 22, 2003

09/14/04

Replace policy - Policy updated with a literature review for the period of May 2002 through May 2004; allogeneic removed from policy statement; autologous remains investigational. Hematopoietic in the title is replaced with Autologous. Approved by OAP 10/29/04, no need to go back to MPC.

10/11/05

Replace policy - Policy updated with literature search; no clinical trial publications found. No change in policy statement. To OAP 10/27/05.

06/02/06

Disclaimer and Scope update - No other changes

09/12/06

Replace policy - Policy updated with literature search; references added; no change to policy statement.

02/22/07

Codes and References Updated - Policy reviewed and recommended by OAP on February 22, 2007. No other changes.

11/13/07

Replace policy - Policy updated with literature review; references added; no change to policy statement.

05/13/08

Cross Reference Update - No other changes

12/16/08

Replace policy - Policy updated with literature search; no change to policy statement. Reference added.

09/15/09

Replace policy - Policy updated with literature search; no change to policy statement. Reference added. Policy reviewed and recommended by OAP on February 19, 2009.

02/09/10

Code Update - New 2010 codes added.

12/14/10

Replace policy - Reviewed and recommended by OAP on November 18, 2010. Policy updated with literature search through August 2010. Reference 13 has been updated; the policy statement remains unchanged.

10/11/11

Replace policy – Policy updated with literature search through August 2011. No references added. Policy statement unchanged. ICD-10 codes added. Codes 38220 and 38221 removed.

01/25/12

Code 38232 added.

02/10/12

The CPT code 38204 was removed from the policy.

06/20/12

Minor update: Related Policies updated; 8.01.17 replaced 8.01.507 effective June 12, 2012.

07/30/12

Updated titles to Related Policies: 8.01.17, 8.01.22, 8.01.26, 8.01.27, 8.01.29, 8.01.30, 8.01.35 and 8.01.520.

12/19/12

Replace policy. Related policies updated with addition of 8.01.25, 8.01.54. Rationale section revised based on a literature review through August 2012. Reference 12 added; others renumbered or removed. Code 41.00 added. Policy statement unchanged. Reviewed and recommended by OAP November, 2012.

02/01/13

Update Related Policies, change title of policy 8.01.21.

03/20/13

The following codes were removed from the policy, as they were not suspending and just informational: HCPCS J9000-J999 and Q0083 – Q0085.

09/27/13

Replace policy. Policy updated with literature search through June 7, 2013. NCCN guidelines updated; no new references added. Policy statement unchanged.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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