BlueCross BlueShield of Tennessee Medical Policy Manual

Hematopoietic Stem Cell Transplantation in the Treatment of Germ Cell Tumors

DESCRIPTION

Hematopoietic stem cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in individuals who receive bone marrow-toxic doses of cytotoxic drugs with or without whole body radiation.  Stem cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT).  They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue in autologous HCT. However, immunologic compatibility between donor and patient is a critical factor for achieving a good outcome of allogeneic HCT. Compatibility is established by typing of human leukocyte antigens (HLA) using cellular, serologic, or molecular techniques.

Germ cell tumors are composed primarily of testicular neoplasms (seminomas or nonseminomatous tumors) but also include ovarian and extragonadal germ cell tumors (e.g., retroperitoneal or mediastinal tumors).  Germ cell tumors are classified according to their histology, stage, prognosis and response to chemotherapy.

Histologies include seminoma, embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumor and mixed germ cell tumors.  Seminomas are the most common; all other types are collectively referred to as nonseminomatous germ cell tumors.  Tumors with mixed histology or seminomas with elevated alpha fetoprotein (due to mixture with nonseminomatous components) are categorized as nonseminomatous tumors.

National Comprehensive Cancer Network’s Risk Classification of Testicular Cancer (post-orchiectomy)

Risk Status

Nonseminoma

Seminoma

Good Risk

Testicular or retroperitoneal primary tumor

No pulmonary visceral metastases

All of the following markers:

AFP < 1,000 ng/ml

hCG < 5,000 iu/L

LDH < 1.5 x upper limit of normal

Any primary site

No pulmonary visceral metastases

Normal AFP

Any hCG and LDH

Intermediate Risk

Testicular or retroperitoneal primary tumor

No pulmonary visceral metastases

All of the following markers:

AFP < 1,000-10,000 ng/ml

hCG < 5,000-50,000 iu/L

LDH < 1.5-10 x upper limit of normal

Any primary site

No pulmonary visceral metastases

Normal AFP

Any hCG and LDH

Poor Risk

Mediastinal primary tumor

Nonpulmonary visceral metastases

Any of the following markers:

AFP > 10,000 ng/ml

hCG > 50,000 iu/L

LDH > 10 x upper limit of normal

No individuals in this classification

Germ-cell tumor prognostic factor categories are based on histology, location, extent of primary tumor, and on certain serum hormone and protein levels or markers. Markers used for germ-cell tumors include human beta-chorionic gonadotropin (hCG), lactate dehydrogenase (LDH), and alpha fetoprotein (AFP).  Germ cell tumors are divided into good, intermediate or poor risk categories based on histology, location, extent of primary tumor, and on serum marker levels. Therapy for germ cell tumors is generally dictated by several factors, including disease stage, tumor histology, site of tumor primary and response to chemotherapy. 

POLICY

See also:

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION

There are scant data in the literature to support the use of allogeneic hematopoietic stem cell transplantation in the treatment of germ cell tumors.

SOURCES    

BlueCross BlueShield Association. Medical Policy Reference Manual. (4:2015). Hematopoietic stem cell transplantation in the treatment of germ cell tumors (8.01.35). Retrieved August 9, 2017 from BlueWeb. (20 articles and/or guidelines reviewed)

Centers for Medicare & Medicaid Services. CMS.gov. (2010, November) NCD for stem cell transplantation (110.8.1). Retrieved August 9, 2017 from http://www.cms.gov.

Daugaard, G., Skoneczna, I., Aass, N., DeWit, R., DeSantis, M., Dumez, H., et al. (2011). A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo germinal (EORTC 30974).  Annals of Oncology, 22 (5), 1054-1061. (Level 2 evidence)

Lorch, A., Kleinhans, A., Kramar, A, Kollmannsberger, C., Hartmann, J., Bokemeyer, C., et al. (2012). Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial. Journal of Clinical Oncology, 30 (8), 800-805. (Level 2 evidence)

National Cancer Institute. (2016). Ovarian germ cell tumors treatment (PDQ®). Treatment options for recurrent ovarian germ cell tumors. Retrieved September 21, 2016 from www.cancer.gov.

National Cancer Institute. (2016). Testicular cancer treatment (PDQ®). Treatment options for recurrent testicular cancer. Retrieved September 21, 2016 from www.cancer.gov.

National Comprehensive Cancer Network. (2016, December). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Testicular cancer V2.2017. Retrieved August 9, 2017 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2017, June). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer V2.2017. Retrieved August 9, 2017 from the National Comprehensive Cancer Network.

Pal, S., Yamzon, J. Sun, V., Carmichael, C., Saikia,  J.  Ferrell, B., et al. (2013, June) Paclitaxel-based high-dose chemotherapy with autologous stem cell rescue for relapsed germ cell tumor: Clinical outcome and quality of life in long-term survivors. Clinical Genitourinary Cancer, 11(2), 121-127. (Level 3 evidence)

ORIGINAL EFFECTIVE DATE:  12/11/2010

MOST RECENT REVIEW DATE:  9/14/2017

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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