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Background: Female survivors of childhood cancers are at increased risk for NSPM, cessation of menses prior to age 40 not secondary to resection of reproductive organs. Our aims ere to assess prevalence of and risk factors for NSPM and to examine the implications of NSPM on reproductive outcomes. Methods: Participants included 2930 female survivors diagnosed beteen 1970 and 1986 and enrolled in the original CCSS cohort median age at diagnosis 6 years, range 0-20; median age at follo-up 34 years; range 18-59 ho ere older than age 18 at last follo-up ithout prior acute ovarian failure. They ere compared to 1399 siblings median age 38 years, range 19-63 . Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates ere compared beteen survivors ith and ithout NSPM. Results: 110 survivors developed NSPM [median age 32, range 16-40, prevalence of 9.1 percent at age 40 95 percent CI 4.9-17.2 , relative risk 10.5 95 percent CI 4.2-26.3 compared to siblings 0.9 percent at age 40, 95 percent CI 0.4-2.3 ]. The prevalence as highest among survivors ho received cyclophosphamide equivalent dose CED 6000 mgm2 18.7 percent at age 40 or 5Gy RT to the ovaries 24.1 percent . Among survivors, independent risk factors included age 14 at diagnosis odds ratio [OR] 2.3, 95 percent Confidence Interval [CI] 1.4-3.8 , CED 6,000 mgm2 OR 3.6, 95 percent CI 2.1-6.3; referent group: CED=0 , and any dose of RT to the ovaries lt5Gy, OR 4.0, 95 percent CI 1.9-8.5; 5Gy, OR 20.4, 95 percent CI 7.8-53.5 . Compared to survivors ithout NSPM, those ho developed NSPM ere less likely to ever be pregnant OR 0.41, 95 percent CI 0.22-0.68 or have a live birth OR 0.35, 95 percent CI = 0.16-0.66 beteen the ages of 31-40. The same comparisons ere not significant beteen the ages of 21-30. Conclusions: Ongoing follo-up of the original CCSS cohort enabled us to identify a threshold exposure to alkylating agents and older age at diagnosis as increasing the risk for NSPM among survivors. The development of NSPM is associated ith loer rates of pregnancy and live birth after age 31. This information ill assist clinicians counseling patients about their risk for early menopause and need for alternative reproductive options.,J Clin Oncol 34, 2016 suppl; abstr 10504 00:00.0,Pediatric Oncology I