Latest Review Date: January 2024

KEY POINTS:

The most recent update occurred through November 15, 2023.

Summary of Evidence

Autologous Hematopoietic Cell Transplantation

For individuals who have adult soft tissue sarcomas who receive autologous HCT, the evidence includes two RCTs, phase two single-arm studies (some of which have been summarized in a systematic review), and a retrospective registry study. Relevant outcomes are overall survival (OS), disease-specific survival, and treatment-related mortality and morbidity. Although a phase 2 RCT reported longer survival for individuals treated with autologous HCT than with standard chemotherapy, this trial did not show a survival benefit with HCT. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have small cell lung cancer who receive autologous HCT, the evidence includes several RCTs, and systematic reviews of these studies. Relevant outcomes are OS, disease-specific survival, and treatment-related mortality and morbidity. Studies have not reported increased OS for individuals with small-cell lung cancer treated with autologous HCT. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Allogeneic Hematopoietic Cell Transplantation

For individuals who have renal cell carcinoma, colorectal cancer, pancreatic cancer, or nasopharyngeal cancer who receive allo-HCT, the evidence includes single-arm series. Relevant outcomes are OS, disease-specific survival, and treatment-related mortality and morbidity. The evidence for allo-HCT to treat renal cell carcinoma, colorectal cancer, pancreatic cancer, and nasopharyngeal cancer has been limited to case series. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

Current National Comprehensive Cancer Network guidelines (2022) on the tumors addressed in this evidence review do not discuss hematopoietic cell transplantation (HCT) as a treatment option and these tumors are also not addressed in the NCCN HCT guideline.

American Society for Blood and Marrow Transplantation

In 2015, the American Society for Blood and Marrow Transplantation (now referred to as the American Society for Transplantation and Cellular Therapy) issued guidelines related to indications for autologous and allogeneic hematopoietic cell transplantation.The guidelines were updated in 2020. The tumors addressed herein for which the Society has provided recommendations are listed in Table 1.

Table 1. Recommendations for Use of Autologous and Allogeneic HCT

HCT: hematopoietic cell transplantation

U.S. Preventive Services Task Force Recommendations

Not Applicable.

KEY WORDS:

High-Dose Chemotherapy, Miscellaneous Solid Tumors, Lung Cancer, Stem-Cell Transplant, Adults, HCT, autologous HCT, Allogeneic HCT, cancer of the bile duct, cancer of fallopian tubes, cervical cancer, esophageal cancer, colon cancer, gall bladder cancer, malignant melanoma, nasopharyngeal cancer, neuroendocrine cancer, pancreatic cancer, prostate cancer, rectal cancer, soft tissue sarcoma, stomach cancer, thyroid tumors, tumors of thymus, tumor of unknown primary origin, uterine cancer, paranasal sinus cancer

APPROVED BY GOVERNING BODIES:

The FDA 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:

HCPCS Codes:

REFERENCES:

1. Abe Y, Ito T, Baba E et al. Nonmyeloablative allogeneic hematopoietic stem cell transplantation as immunotherapy for pancreatic cancer. Pancreas. Oct 2009; 38(7):815-819.
2. Aglietta M, Barkholt L, Schianca FC et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adaptive cell therapy approach. The European Group for Blood and Marrow Transplantation experience. Biol Blood Marrow Transplant.Mar 2009; 15(3):326-335.
3. Airoldi M, De Crescenzo A, Pedani F et al. Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma. Head Neck. Sep 2001; 23(9):799-803.
4. American Society of Clinical Oncology (ASCO). Sarcoma, Soft Tissue: Statistics. www.cancer.net/cancer-types/sarcoma-soft-tissue/statistics. Updated March 2023.
5.  Bregni M, Bernardi M, Servida P, et al. Long-term follow-up of metastatic renal cancer patients undergoing reduced-intensity allografting. Bone Marrow Transplant. Aug 2009; 44(4):237-242.
6. Bui-Nguyen B, Ray-Coquard I, Chevreau C, et al. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial. Ann Oncol. Mar 2012; 23(3):777-784.
7. Cancer disparities. National Cancer Institute. https://www.cancer.gov/about-cancer/understanding/disparities. Published March 28, 2022. Accessed February 7, 2023.
8. Carnevale-Schianca F, Ricchiardi A, Capaldi A et al. Allogeneic hemopoietic stem cell transplantation in solid tumors. Transplant Proc 2005; 37(6):2664-2666.
9. Childs R, Chernoff A, Contentin N et al. Regression of metastatic renal cell carcinoma after nonmyeloablative allogeneic peripheral blood stem cell transplantation. N Engl J Med. Sep 14 2000; 343(11):750-758.
10. Crivellari G, Monfardini S, Stragliotto S et al. Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to megadoses. Oncologist. Jan 2007; 112(1):79-89.
11. Demirer T, Barkholt L, Blaise D et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Clin Pract Oncol. May 2008; 5(5):256-267.
12. Dirksen U, Brennan B, Le Deley MC, et al. High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. J Clin Oncol. Dec 01 2019; 37(34): 3192-3202.
13. Hartmann JT, Horger M, Kluba T, et al. A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high dose ICE consolidation with PBSCT in non-resectable, high grade, adult type soft tissue sarcomas. Invest New Drugs. Dec 2013; 31(6):1592-1601.
14. Heilig CE, Badoglio M, Labopin M, et al. Haematopoietic stem cell transplantation in adult soft-tissue sarcoma: an analysis from the European Society for Blood and Marrow Transplantation. ESMO Open. Oct 2020; 5(5).
15. Imanguli MM, Childs RW. Hematopoietic stem cell transplantation for solid tumors. Update Cancer Ther 2006; 1(3):343-352. 
16. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
17. Jiang J, Shi HZ, Deng JM et al. Efficacy of intensified chemotherapy with hematopoietic progenitors in small-cell lung cancer: a meta-analysis of the published literature. Lung Cancer. Aug 2009; 65(2):214-218.
18. 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.
19. Kanda Y, Omuro Y, Baba E et al. Allo-SCT using reduced-intensity conditioning against advanced pancreatic cancer: a Japanese survey. Bone Marrow Transplant. Jul 2008; 42(2):99-103.
20. Kasper B, Dietrich S, Mechtersheimer G et al. Large institutional experience with dose-intensive chemotherapy and stem cell support in the management of sarcoma patients. Oncology 2007; 73(1-2):58-64.
21. Kasper B, Scharrenbroich I, Schmitt T et al. Consolidation with high-dose chemotherapy and stem cell support for responding patients with metastatic soft tissue sarcomas: prospective, single-institutional phase II study. Bone marrow Transplant. Jul 2010; 45(7): 1234-1238.
22. Lee JA, Choi SY, Kang HJ, et al. Treatment outcome of osteosarcoma after bilateral retinoblastoma: a retrospective study of eight cases. Br J Opthalmol. Oct 2014; 98(10):1355-1359.
23. Lorigan P, Woll PJ, O’Brien ME et al. Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. J Natl Cancer Inst. Mar 04 2005; 97(9):666-674.
24. 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. 
25. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: hematopoietic cell transplantation. Version 3.2023.
26. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: soft tissue sarcoma. Version 2.2023. www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. 
27. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: kidney cancer. Version 1.2024. www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. 
28. National Comprehensive Cancer Network (NCCN). NCCN guidelines & clinical resources. www.nccn.org/professionals/physician_gls/default.aspx. 
29. Nishimura M, Nasu K, Ohta H et al. High dose chemotherapy for refractory urothelial carcinoma supported by peripheral blood stem cell transplantation. Cancer. Nov 01 1999; 86(9):1827-1831.
30. Omazic B, Ayoglu B, Löhr M, et al. A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer. J Immunother. May 2017; 40(4): 132-139. 
31. Omazic B, Remberger M, Barkholt L, et al. Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation for Solid Cancer. Biol Blood Marrow Transplant. Apr 2016; 22(4):676-681.
32. Pedrazzoli P, Ledermann JA, Lotz JP et al. High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol 2006; 17(10):1479-88.
33. Peinemann F, Enk H, Smith LA. Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas. Cochrane Database Syst Rev. Apr 13 2017; 4:CD008216.
34. Peinemann F, Labeit AM. Autologous haematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas: a Cochrane systematic review*. BMJ Open. Jan 29 2014; 4(7):e005033.
35. Schlemmer M, Wendtner CM, Falk M et al. Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas. Oncology 2006; 71(1-2):32-39.
36. Toh HC, Chia WK, Sun L et al. Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation. Bone Marrow Transplant. Apr 2011; 46(4): 573-579.

POLICY HISTORY:

Medical Policy Panel, September 2010

Medical Policy Group, January 2011 (2):  New policy

Medical Policy Administration Committee, February 2011

Available for comment February 24th through April 11, 2011

Medical Policy Group, September 2011 (3): Updated Key Points, Key Words & HCPC Codes

Medical Policy Group, December 2011 (3): 2012 Code Updates: Updated codes 38208 & 38209. Added codes 38230 & 38323

Medical Policy Panel, October 2012.

Medical Policy Group, January 2013 (3): 2012 Update to Key Points & References

Medical Policy Panel, October 2013

Medical Policy Group, October 2013 (3):  2013 Update to Key Points; no change in policy statement

Medical Policy Panel, January 2015

Medical Policy Group, January 2015 (3): Update to Description, Key Points and References. No change in policy statement.

Medical Policy Panel, January 2016

Medical Policy Group, February 2016 (2): Updates to Description, Key Points, Approved Governing Bodies, Key Words and References. Removed HCPCS codes Q0083-Q0085 and J9000-J9999 from policy; No change to policy statement.

Medical Policy Panel, January 2017

Medical Policy Group, January 2017 (7): Updates to Title, Description, Key Points, and References; No change to policy statement.

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, January 2018 (7): Updates to Description, Key Points, and References.  No change to policy statement.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): 2019 Updates to Key Points, References and Key Words: added: Paranasal Sinus Cancer. No changes to policy statement or intent. Removed effective dates in coding section from 2012.

Medical Policy Panel, January 2020

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

Medical Policy Panel, January 2021

Medical Policy Group, February 2021 (3): 2021 Updates to Key Points, Practice Guidelines and Position Statements, and References. Policy statement updated to remove “not medically necessary,” no change to policy statement or intent.

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, February 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 Descriptions, 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.