Open AccessPhase II Study of Gonadotropin‐Releasing Hormone Analog for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
Author(s) -
Cheng Yee Chung,
Takagi Mariko,
Milbourne Andrea,
Champlin Richard E.,
Ueno Naoto T.
Publication year - 2012
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2011-0205
Subject(s) - medicine , hematopoietic stem cell transplantation , hormone , transplantation , stem cell , haematopoiesis , gonadotropin , hematopoietic cell , oncology , hematopoietic stem cell , microbiology and biotechnology , biology
Purpose. Premature ovarian failure occurs in 40%–70% of patients who receive conventional chemotherapy alone. However, the incidence is higher, 70%–100%, in patients who undergo myeloablative chemotherapy with hematopoietic stem cell transplantation (HSCT). Gonadotropin‐releasing hormone (GnRH) analogs, such as leuprolide, in a continuous‐release formulation, may protect the ovaries from the gonadotoxic effects of chemotherapy. In non‐HSCT settings, GnRH analogs have reduced the risk for premature ovarian failure to <10%. We conducted a phase II clinical trial based on the hypothesis that giving leuprolide before conditioning chemotherapy in HSCT patients reduces premature ovarian failure incidence. Patients and Methods. Eligible patients were women aged ≤40 years who were HSCT candidates, were premenopausal, and had both follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) levels ≤20 IU/L. Two 22.5‐mg leuprolide doses were delivered in 3‐month depot i.m. injections, the first within 2 months before HSCT. Patients were monitored for menstruation return, and ovarian function tests (FSH, LH, and estradiol) were done every 2 months starting 90 days after the last leuprolide dose. Results. Sixty eligible patients were enrolled, 59 underwent HSCT, and 44 were evaluable (median age, 25 years; median follow‐up, 355 days). Only seven of 44 patients (16%) regained ovarian function. Of the 33 who received myeloablative regimens, six (18%) regained ovarian function. However, among the 11 who received nonmyeloablative regimens, only one (9%) regained ovarian function ( p = .66). Conclusion. Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated.