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Hematopoietic Cell Transplantation for Epithelial Ovarian Cancer

Policy Number: MP-401

Latest Review Date: January 2022

Category:  Surgery                                                                 


Autologous or allogeneic hematopoietic stem-cell transplantation is considered investigational to treat advanced stage epithelial ovarian cancer.


Cord blood transplantation is discussed in greater detail in policy # 439 Placental/Umbilical Cord Blood as a Source of Stem Cells.

Stem cell transplantation to treat germ cell tumors of the ovary is considered separately in policy #412 Hematopoietic Cell Transplantation in the Treatment of Germ-Cell Tumors.


The use of hematopoietic cell transplantation (HCT) has been investigated for treatment of patients with epithelial ovarian cancer. Hematopoietic stem cells are infused to restore bone marrow function following cytotoxic doses of chemotherapeutic agents with or without whole body radiotherapy.

Epithelial Ovarian Cancer

Several types of malignancies can arise in the ovary; epithelial carcinoma is the most common. New cases and deaths from ovarian cancer in the United States for 2021 were estimated at 21,410 and 13,770 respectively. Most ovarian cancer patient's present with widespread disease, and the National Cancer Institute Surveillance, Epidemiology and Results Program reported a 49.4% five-year survival for all cases between 2011 and 2017.

The current management of advanced epithelial ovarian cancer is cytoreductive surgery with chemotherapy. Approximately 75% of patients present with International Federation of Gynecology and Obstetrics (FIGO) Stage III to IV ovarian cancer, are treated with the combination of paclitaxel plus a platinum analog, the preferred regimen for newly diagnosed advanced disease. The use of platinum and taxanes has improved progression-free survival (PFS) and overall survival (OS) rates in advanced disease to 16–21 months and 32–57 months, respectively. However, most of these patients develop recurrences and die of their disease as chemotherapy drug resistance leads to uncontrolled cancer growth.

Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) 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 radiotherapy. Bone marrow stem cells may be obtained from the transplant recipient (autologous HCT) or from a donor (allogeneic HCT). They 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.

HCT is an established treatment for certain hematologic malignancies; however, its use in solid tumors in adults continues to be largely experimental.

HCT for Epithelial Ovarian Cancer

High-dose chemotherapy (HDC) has been investigated as a therapy to overcome drug resistance. However, limited data exist on this treatment approach, and the ideal patient population and best regimen remain to be established. Hematopoietic cell transplantation has been tested in various patient groups with ovarian cancer as follows:

  • to consolidate remission after initial treatment

  • to treat relapse after a durable response to platinum-based chemotherapy

  • to treat tumors that relapsed after less than 6 months

  • to treat refractory tumors


The most recent update covered the period through November 22, 2021.

Summary of Evidence

For individuals who have advanced-stage epithelial ovarian cancer who receive HCT, the evidence includes randomized trials and data from case series and registries. Relevant outcomes are overall survival, disease-specific survival, change in disease status, and treatment related mortality and morbidity. Although some of the observational studies have reported longer survival in subsets of patients with advanced epithelial ovarian cancer than patients treated with standard chemotherapy, none of the randomized trial evidence has shown a benefit from HCT in this population. Overall, the evidence has not shown that HCT improves health outcomes in treating epithelial ovarian cancer, including survival, compared with conventional standard doses of chemotherapy. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

The current NCCN guidelines on ovarian cancer including fallopian tube cancer and primary peritoneal cancer (v.3.2021) do not address HCT for epithelial ovarian cancer for either newly diagnosed patients, nor for patients with relapsed or refractory disease.

Accordingly, NCCN guidelines on HCT (v.5.2021) do not reference epithelial ovarian cancer as an indication for HCT.

U.S. Preventive Services Task Force Recommendations

Hematopoietic cell transplantation is not a preventive service.


High-Dose Chemotherapy, Ovarian, Epithelial, HCT, hematopoietic cell transplant, epithelial ovarian cancer, autologous, allogeneic


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.


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. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.


CPT Codes:


Management of recipient hematopoietic cell donor search and cell acquisition


Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic


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


Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing; per donor


; thawing of previously frozen harvest, with washing; per donor


; specific cell depletion with harvest, T-cell depletion


; tumor cell depletion


; red blood cell removal


; platelet depletion


; plasma (volume) depletion


; cell concentration in plasma, mononuclear, or buffy coat layer


Diagnostic bone marrow; aspiration(s)


Diagnostic bone marrow; biopsy(ies),


Diagnostic bone marrow; biopsy(ies) and aspiration(s) (Effective 01/01/2018)


Bone marrow harvesting for transplantation; allogeneic


  ; autologous (Effective January 1, 2012)


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


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


Bone marrow or blood-derived peripheral stem-cell transplantation; allogeneic donor lymphocyte infusions



Cord blood harvesting for transplantation, allogeneic


Cord blood derived stem-cell transplantation, allogeneic


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 on the global definition (including drugs; hospitalization; medical surgical, diagnostic and emergency services)                                   


  1. American Cancer Society. Cancer Facts & Figures 2017. Atlanta, GA: American Cancer Society; 2017. Accessed December 9, 2020.

  2. American Cancer Society. Cancer Facts & Figures 2014. Atlanta, Ga: American Cancer Society; 2014.

  3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). High-dose chemotherapy with autologous stem-cell support for epithelial ovarian cancer. TEC Assessments. 1998; Volume 13, Tab 6.

  4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Salvage high-dose chemotherapy with allogeneic stem cell support for relapse following high-dose chemotherapy with autologous stem cell support for non-lymphoid solid tumors. TEC Assessments. 1999; Volume 14, Tab 11.

  5. Cure H, Battista C, Guastalla JP, et al.  Phase III randomized trial of high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support as consolidation in patients (pts) with advanced ovarian cancer (AOC): 5-year follow-up of a GINECO/FNCLCC/SFGM-TC study. Abstract No: 5006. American Society for Clinical Oncology. 40th annual meeting. New Orleans, Louisiana. June 5-8, 2004.

  6. Donato ML, Aleman A, Champlin RE, et al. Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation.  Bone Marrow Transplant 2004; 33(12):1219-1224.

  7. Ledermann JA, Herd R, Maraninchi D, et al. High-dose chemotherapy for ovarian carcinoma: long-term results from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol 2001; 12(5):693-699.

  8. Mobus V, Wandt H, Frickhofen N, et al. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: Intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol 2007; 25(27):4187-4193.

  9. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 2.2016.

  10. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation (HCT): Pre-Transplant Recipient Evaluation and Management of Graft-Versus-Host Disease. Version 2.2020. Accessed December 9, 2020.

  11. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Version 1.2020. Accessed December 10, 2020.

  12. National Cancer Institute, Surveillance Epidemiology and End Results Program. Cancer Stat Facts: Ovarian Cancer. n.d.; Accessed December 9, 2020.

  13. Papadimitriou C, Dafni U, Anagnostopoulos A, et al. High-dose melphalan and autologous stem cell transplantation as consolidation treatment in patients with chemosensitive ovarian cancer: Results of a single-institution randomized trial. Bone Marrow Transplant 2008; 41(6):547-554.

  14. Physician Data Query (PDQ), 2008. Ovarian epithelial cancer treatment (PDQ®). National Cancer Institute, U.S. National Institute of Health.

  15. Sabatier R, Goncalves A, Bertucci F et al. Are there candidates for high-dose chemotherapy in ovarian carcinoma? J Exp Clin Cancer Res 2012; 31:87.

  16. Stiff PJ, Veum-Stone J, Lazarus HM, et al. High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report. Ann Intern Med 2000; 133(7):504-515.

  17. Stiff PJ, Bayer R, Kerger C, et al. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients. J Clin Oncol 1997; 15(4):1309-1317.


Medical Policy Group, January 2010 (2)

Medical Policy Administration Committee, January 2010

Available for comment January 26-March 11, 2010

Medical Policy Group, November 2010 (1): Description updated, Key Points updated, no policy change

Medical Policy Group, December 2011 (3): 2012 Code Updates: Verbiage update to Codes 38208, 38209 & 38230; Added Code 38323

Medical Policy Group, February 2012 (2): Updated Description and Key Points

Medical Policy Group, January 2013 (2): 2013 Update to Key Points. No change in the policy statement.

Medical Policy Panel, November 2013

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

Medical Policy Panel, November 2014

Medical Policy Group, November 2014 (3): Updates to Description, Key Points and Approved Governing Bodies. No Policy change.

Medical Policy Panel, January 2016.

Medical Policy Group, February 2016 (2): Updates to Description, Key Points, Approved Governing Bodies, Key Words, and References.  No change to policy statement.

Medical Policy Panel, January 2017

Medical Policy Group, January 2017 (7): Updates to Title, Description, added Key Points. No new References added. 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): 2018 Updates to Description, Key Points and References. Policy statement clarified to add “advanced stage” associated with epithelial ovarian cancer; no change in intent.

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (3): Updates to Key Points and References. No change to policy statement or intent.

Medical Policy Panel, January 2020

Medical Policy Group, January 2020 (3): 2020 Updates to Key Points and References. Policy Guidelines section added. No changes to policy statement or intent.

Medical Policy Panel, January 2020

Medical Policy Group, January 2020 (3): Updates to Description, Key Points, and References.

Medical Policy Panel, January 2022

Medical Policy Group, January 2022 (3): 2022 Updates to Description, Key Points, and Practice Guidelines and Position Statements. 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.