Chemotherapy-Related Amenorrhea (CRA) among Premenopausal Patients Treated for Acute Leukemia.

Background: Little is known about the late effects of treatment for acute leukemia on ovarian function. We sought to evaluate the rate of long-term chemotherapy-related amenorrhea (CRA) among premenopausal women treated for acute leukemia.

Methods: The Cleveland Clinic database of patients treated for acute leukemia between July 1994 and July 2005 was searched for patients aged 15–44 at diagnosis who were believed to be alive. Thirty of 69 identified patients were excluded due to active disease, on-going treatment or lost to follow-up. Questionnaires regarding menstrual and fertility history were mailed to the remaining 39 patients.

Results: Twenty-five patients responded to the questionnaire, 4 of whom were excluded due to lack of menses at the time of diagnosis (n=2), use of Depo-provera at time of diagnosis (n=1) or use of Depo-provera at time of f/u (n=1). The median age of the remaining 21 patients was 30 (range 15 to 44). Thirteen patients had AML and 8 had ALL. Nine of the 21 had undergone myeloablative transplant, 8 allogeneic and 1 autologous. Median f/u time from treatment was approximately 43 months (range 9 to 141). Long-term CRA occurred in 8/21 patients (38%). Only 2/12 patients (17%) who received standard-dose chemotherapy alone had persistent CRA while 6/9 (67%) of those undergoing transplant had persistent CRA (p=0.032, Fisher’s Exact test). The incidence of CRA increased with age: 0/3 patients under age 18, 1/4 patients age 18–25, and 7/14 patients age 26–44 at treatment remained amenorrheic (p=0.042, 1-sided Cochran-Armitage test). Only 2 patients reported attempts at fertility following treatment. One patient reported delivering three children, the other patient was amenorrheic and was undergoing fertility treatment.

Conclusions: These findings suggest that a substantial minority of young survivors of acute leukemia will experience premature ovarian failure. Increasing age at treatment and transplant are associated with a greater risk of long-term CRA.