BlueCross BlueShield of Tennessee Medical Policy Manual

Hematopoietic Stem Cell Transplantation in the Treatment of Germ Cell Tumors


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.

Germ cell tumors are composed primarily of testicular neoplasms as well as ovarian and extragonadal germ cell tumors (no primary tumor in either testis or ovary). Germ cell tumors are classified by their histology, stage, prognosis, and response to chemotherapy. The most common testicular germ cell tumors are seminomas; all other histologic types are collectively referred to as nonseminomatous tumors. Nonseminomatous tumor types include embryonal cell tumor, yolk sac tumor, and teratomas. Malignant germ cell tumors of ovarian origin are classified as dysgerminomas or nondysgerminomas. Similarly, nondysgerminomas include immature teratomas, embryonal cell tumors, yolk sac tumor, polyembryoma, and mixed germ cell tumors.

Therapy for germ cell tumors is generally dictated by several factors, including disease stage, tumor histology, site of primary tumor and response to chemotherapy. Individuals with favorable prognostic factors include those with a testis or retroperitoneal primary site, a complete response to initial chemotherapy, low levels of serum markers, and low volume disease. Individuals with unfavorable prognostic factors are those with an incomplete response to initial therapy or relapsing mediastinal nonseminomatous germ cell tumors. Autologous stem cell transplantation may be a second-line treatment option for individuals who have relapsed.





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


BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2018). Hematopoietic cell transplantation in the treatment of germ cell tumors (8.01.35). Retrieved July 10, 2018 from BlueWeb. (20 articles and/or guidelines reviewed)

Centers for Medicare & Medicaid Services. (2016, October). NCD for stem cell transplantation (110.23). Retrieved July 11, 2018 from

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 Comprehensive Cancer Network. (2018, February). NCCN Clinical Practice Guidelines in Oncology (NCCN GuidelinesĀ®). Testicular cancer V2.2018. Retrieved July 11, 2018 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2018, March). NCCN Clinical Practice Guidelines in Oncology (NCCN GuidelinesĀ®). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer V2.2018. Retrieved July 11, 2018 from the National Comprehensive Cancer Network.

Pal, S., Yamzon, J. Sun, V., Carmichael, C., Saikia, J.  Ferrell, B., et al. (2013). 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)

Suleiman, Y., Siddiqui, B.K., Brames, M.J., Abonour, R., & Einhorn, L.H. (2013). Salvage therapy with high-dose chemotherapy and peripheral blood stem cell transplant in patients with primary mediastinal nonseminomatous germ cell tumors. Biology of Blood and Marrow Transplantation, 19 (1), 161-163. Abstract retrieved July 11, 2018 from PubMed database.




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