Medical policy: Hematopoietic Cell Transplantation for Miscellaneous Solid Tumors in Adults

Policy number: MP 9.048

Effective date: 5/1/2026

Policy

Autologous or allogeneic hematopoietic cell transplant is considered investigational for the following malignancies in adults. There is insufficient evidence to support a general conclusion concerning the health outcomes or benefits associated with this procedure.

• Lung cancer, any histology
• Colon cancer
• Rectal cancer
• Pancreatic cancer
• Stomach cancer
• Esophageal cancer
• Gall bladder cancer
• Cancer of the bile duct
• Renal cell cancer
• Cervical cancer
• Uterine cancer
• Cancer of the fallopian tubes
• Prostate cancer
• Nasopharyngeal cancer
• Paranasal sinus cancer
• Neuroendocrine tumors
• Soft tissue sarcomas
• Thyroid tumors
• Tumors of the thymus
• Tumors of unknown primary origin
• Malignant melanoma

Cross-references

• MP 9.001 Placental/Umbilical Cord Blood as a Source of Stem Cells
• MP 9.047 Hematopoietic Cell Transplantation for Epithelial Ovarian Cancer
• MP 9.050 Hematopoietic Cell Transplantation for CNS Embryonal Tumors and Ependymoma
• MP 9.054 Hematopoietic Cell Transplantation for Solid Tumors of Childhood
• MP 9.052 Hematopoietic Cell Transplantation in the Treatment of Germ-Cell Tumors

Product variations

This policy is only applicable to certain programs and products administered by Capital Blue Cross and subject to benefit variations. Please see additional information below.

FEP PPO - Refer to FEP Medical Policy Manual.

Description/background

Hematopoietic cell transplantation (HCT) is an established treatment for certain hematologic malignancies and has been investigated for a variety of adult solid tumors. Interest continues in exploring nonmyeloablative allogeneic HCT (allo-HCT) for a graft-versus-tumor effect of donor-derived T-cells in metastatic solid tumors.

Hematopoietic cell transplantation

Hematopoietic cell transplantation (HCT) is 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 radiotherapy. Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the United States annually. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or from a donor (allogeneic HCT [allo-HCT]). They can be harvested from bone marrow, peripheral blood, or from umbilical cord blood shortly after delivery of neonates. Cord blood is discussed in detail in MP 9.001 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 6. An acceptable donor will match the patient at all or most of the HLA loci.

Conditioning for HCT

Conventional conditioning

The conventional (“classical”) practice of allo-HCT involves the 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 potentially curative, it may be overwhelmed by extensive disease without the use of pretransplant conditioning. However, 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 caused by cytotoxic drugs. Subsequent to graft infusion in allo-HCT, immunosuppressant drugs are required to minimize graft rejection and graft-versus-host disease (GVHD), which increases susceptibility to opportunistic infections.

The success of autologous HCT is predicated on the ability of cytotoxic chemotherapy with or without radiation to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of bone marrow space 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 for allo-HCT

Reduced-intensity conditioning (RIC) 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 RIC is variable, the numerous versions employed all seek to balance the competing effects of relapse due to residual disease and non-relapse mortality.

The goal of RIC is to reduce disease burden and minimize associated treatment-related morbidity and non-relapse mortality in the period during which the beneficial graft-versus-malignancy effect of allogeneic transplantation develops. RIC regimens range from nearly total myeloablative to minimally myeloablative with lymphoablation, with intensity tailored to specific diseases and patient condition. Patients who undergo RIC with allo-HCT initially demonstrate donor cell engraftment and bone marrow mixed chimerism. Most subsequently convert to full donor chimerism. In this review, the term RIC will refer to all conditioning regimens intended to be nonmyeloablative.

HCT in solid tumors in adults

HCT is an established treatment for certain hematologic malignancies. Its use in solid tumors is less well established, although it has been investigated for a variety of solid tumors. With the advent of nonmyeloablative allogeneic transplant, interest has shifted to exploring the generation of alloreactivity to metastatic solid tumors via a graft-versus-tumor effect of donor-derived T cells.

HCT as a treatment for ovarian cancer, germ cell tumors, ependymoma, or malignant glioma is addressed separately. HCT as a treatment for breast cancer is not addressed. This medical policy collectively addresses other solid tumors of adults for which HCT has been investigated, including lung cancer, malignant melanoma, tumors of the gastrointestinal tract (affecting the colon, rectum, pancreas, stomach, esophagus, gallbladder, or bile duct), male and female genitourinary systems (e.g., renal cell carcinoma, prostate cancer, cervical cancer, uterine cancer, fallopian tube cancer), tumors of the head and neck, soft tissue sarcoma, thyroid tumors, tumors of the thymus, and tumors of unknown primary origin.

Current National Comprehensive Cancer Network guidelines on the tumors addressed in this policy do not discuss hematopoietic cell transplantation (HCT) as a treatment option.

Regulatory status

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, title 21, parts 1270 and 1271. Hematopoietic stem cells are included in these regulations.

Rationale

Summary of evidence

Autologous hematopoietic cell transplantation

For individuals who have adult soft tissue sarcomas who receive autologous HCT, the evidence includes 2 randomized controlled trials (RCTs), a number of phase 2 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 small phase 2 RCT reported longer survival for patients 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 patients 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 small 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 small case series. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Definitions

Allogeneic refers to having a different genetic constitution but belonging to the same species, i.e., involves a donor and a recipient. These cells are harvested from a donor, after verifying the donor and the recipient are well matched with respect to human leukocyte antigens (HLA). Allogeneic cells provide two (2) theoretical advantages: the lack of tumor contamination associated with autologous stem cells, and the possibility of a beneficial graft-versus-tumor effect. Their disadvantage is the risk of graft-versus-host disease (GVHD), which increases with greater HLA disparity and recipient age.

Autologous refers to originating within an individual (i.e., self-donation). These stem cells are harvested from patients prior to myeloablative therapy.

Disclaimer

Capital Blue Cross’ medical policies are used to determine coverage for specific medical technologies, procedures, equipment, and services. These medical policies do not constitute medical advice and are subject to change as permitted by law or applicable clinical evidence from independent treatment guidelines. Treating providers are solely responsible for medical advice and treatment of members. These policies are not a guarantee of coverage or payment. Payment of claims is subject to a determination regarding the member’s benefit program and eligibility on the date of service, and a determination that the services are medically necessary and appropriate. Final processing of a claim is based upon the terms of contract that applies to the member’s benefit program, including benefit limitations and exclusions. If a provider or a member has a question concerning this medical policy, please contact Capital Blue Cross’ Provider Services or Member Services.

Coding information

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement.

Investigational when used for treatment of miscellaneous solid tumors listed; therefore, not covered

References

1. Caravelle-Schianca F, Ricciard A, Capaldi A, et al. Allogeneic hemopoietic stem cell transplantation in solid tumors. Transplant Proc. Jul-Aug 2005; 37(6): 2664-6. PMID 16182778
2. American Society of Clinical Oncology (ASCO). Sarcoma, Soft Tissue: Statistics.
3. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: soft tissue sarcoma. Version 3.2023.
4. Pedazzoli 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. Oct 2006; 17(10): 1479-88. PMID 16547069
5. 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. PMID 18334832
6. Schlemmer M, Wendtner CM, Falk M, et al. Efficacy of consolidating 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): 32-9. PMID 17344669
7. Peinemann F, Enk AH, Smith LA. Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas. Cochrane Database Syst Rev. Apr 13 2017; 4: CD008216. PMID 28407197
8. 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): 777-84. PMID 21652583
9. Peinemann F, Labeit AM. Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas: a Cochrane systematic review*. BMJ Open. Jul 29 2014; 4(7): e005033. PMID 25079925
10. 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 of EWING 2008. J Clin Oncol. Dec 01 2019; 37(34): 3192-3202. PMID 31553693
11. 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-institution phase II study. Bone Marrow Transplant. Jul 2010; 45(7): 1234-8. PMID 19935728
12. Hartmann JT, Horger M, Kluab T, et al. A non-comparative phase II study of dose intensive chemotherapy with doxorubicin and ifosfamide followed by high-dose ICE consolidation with PBSC in non-resectable, high grade, adult type soft tissue sarcomas. Invest New Drugs. Dec 2013; 31(6): 1592-601. PMID 24091981
13. Heilig CE, Badoglio M, Labopin M, et al. Hematopoietic 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): e000860. PMID 33097652
14. 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): 214-8. PMID 19118199
15. 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. May 04 2005; 97(9): 666-74. PMID 15870437
16. Crivellari G, Monfardini S, Stragliotto S, et al. Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to megadoses. Oncology. Jan 2007; 12(1): 79-89. PMID 17227903
17. 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): 1827-31. PMID 10547557
18. 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. PMID 11505492
19. Lee JA, Choi SY, Kang HJ, et al. Treatment outcome of osteosarcoma after bilateral retinoblastoma: a retrospective study of eight cases. Br J Ophthalmol. Oct 2014; 98(10): 1355-9. PMID 24795337
20. Imanguli MM, Childs RW. Hematopoietic stem cell transplantation for solid tumors. Update Cancer Ther. 2006; 1(3): 343-352.
21. 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): 256-67. PMID 18398414
22. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: kidney cancer. Version 3.2024.
23. 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): 750-8. PMID 10984562
24. 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): 237-42. PMID 19234510
25. Aglietta M, Barkholt L, Schianca F, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adoptive cell therapy approach. The European Group for Blood and Marrow Transplantation experience. Biol Blood Marrow Transplant. Mar 2009; 15(3): 326-35. PMID 19203723
26. 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. PMID 18391987
27. Abe Y, Ito T, Baba E, et al. Nonmyeloablative allogeneic stem cell transplantation as immunotherapy for pancreatic cancer. Pancreas. Oct 2009; 38(7): 815-9. PMID 19696692
28. Omazic B, Ayoub L, Lohr 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. PMID 28338506
29. 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): 573-9. PMID 20661236
30. 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. PMID 26740375
31. National Comprehensive Cancer Network (NCCN). NCCN guidelines & clinical resources.
32. 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. PMID 26256941
33. 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. PMID 32165328
34. Centers for Medicare & Medicaid Services. National Coverage Determination (NCD) for Stem Cell Transplantation (Formerly 110.8.1) (110.23). Updated January 27, 2016.
35. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: hematopoietic cell transplantation (HCT). Version 3.2025.
36. Snowden JA, Sánchez-Ortega I, Corbacioglu S, et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transplant. 2022; 57(8): 1217-1239. doi:10.1038/s41409-022-01691-v PMID 35589979
37. Forman SJ, Nakamura R. (2015, November 1). Hematopoietic cell transplantation. Cancer Network.
38. Storb RF, Lucarelli G, McSweeney PA, Childs RW. Hematopoietic cell transplantation for benign hematological disorders and solid tumors. Hematology Am Soc Hematol Educ Program. 2003; 372-397. doi:10.1182/asheducation-2003.1.372 PMID 4633791
39. D’Souza A, Fretham C, Lee SJ, et al. Current Use of and Trends in Hematopoietic Cell Transplantation in the United States (published correction appears in Transplant Cell Ther. 2022 Oct;28(10):715-716). Biol Blood Marrow Transplant. 2020;26(8):e177-e182. doi:10.1016/j.bbmt.2020.04.013 PMID 32438042