Summary:We reviewed gonadal function in 270 patients who underwent bone marrow transplantation (BMT) between 1974 and 1988. Age at transplant ranged from 6 to 54 years (mean 25.6 years). Diagnoses included acute myelogenous leukemia, chronic myelogenous leukemia, aplastic anemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin's disease and other diagnoses. Effects of patient characteristics on risk of gonadal dysfunction were analyzed by comparing the cumulative probability of developing gonadal dysfunction over time from BMT. Ninety-two percent of the males and 99% of the females developed evidence of gonadal dysfunction. Females were not only more likely to develop elevated gonadotrophin levels than males, but did so earlier after BMT. Odds ratios were calculated to determine potentially important prognostic factors for the development of an elevated gonadotrophin level. Older age at BMT was correlated with an increased risk in the development of elevated gonadotrophin levels. Individuals who received radiation were more likely to develop an elevated FSH level over time than those who had received no preparative radiation treatment. Males were more likely to experience gonadal recovery than females. In those cases that did recover, males tended to recover more quickly after BMT than females. Keywords: gonadal dysfunction; bone marrow transplant; risk; late effectsThe annual number of bone marrow transplants (BMT) has been steadily increasing since 1980. World-wide, BMTs have increased from 500 in 1980 to over 5000 in 1991. 1 The number of transplants at the University of Minnesota has increased over this time, from 43 in 1980 to 200 in 1990. With the increasing utilization of bone marrow transplantation in the last 20 years, several late effects of BMT, particularly endocrine disturbances, have been described.A number of reports in the literature have detailed endocrine dysfunction in children who have undergone BMT. Cyclophosphamide usage has been reported to cause gona- dal damage in both adults and children, and appears to be dose-related and in some instances reversible in males. [2][3][4] Several studies have shown that high-dose chemotherapy and TBI are associated with gonadal dysfunction and failure of gonadal recovery in females. 4,5 These studies also suggest that recovery of ovarian function, but not recovery of testicular function, is more likely to be seen in those who receive fractionated TBI than in individuals who receive single dose TBI. 3,4 The objectives of this retrospective review of individuals who had undergone BMT at the University of Minnesota were to determine the percentage of individuals who developed gonadal dysfunction after bone marrow transplantation, the time to the first documented evidence of gonadal dysfunction after BMT, and the factors associated with this gonadal dysfunction. This study also sought to determine the percentage of individuals who achieved gonadal recovery following dysfunction, the timing of this recovery, and the factors associated with recover...

Summary:Between 1976 and 1992, 869 patients Ͻ19 years of age underwent BMT at the University of Minnesota for a variety of malignant and non-malignant disorders. One hundred and ninety-six required mechanical ventilation (MV) at some time from the start of pre-BMT cyto reduction through the first year following BMT. Reasons for MV included respiratory compromise, upper airway management and non-pulmonary indications for respiratory support. In multivariate models, underlying diagnosis, receipt of HLA-mismatched marrow and the presence of acute graft-versus-host disease (aGVHD) were independent predictors of the need for MV. Indication for MV, underlying diagnosis, and presence of aGVHD were independent predictors of successful extubation. Overall survival at 2 years was 14% among MV patients and 52% among non-MV patients. While the need for MV during BMT reduces the overall likelihood of survival, 40% of children who required MV were successfully extubated; 35% of these extubated patients were long-term survivors. This outcome is better than that reported for adult BMT patients requiring respiratory support, who show survival of Ͻ5% at 6 months following BMT. Our data suggest extrapolation of outcome data from adult to pediatric patients is not appropriate and aggressive care of pediatric patients requiring respiratory support is not futile.

Many reports suggest that physically active women have a somewhat lower breast cancer incidence than physically inactive women. We hypothesized that indices of physical activity are associated inversely with breast cancer incidence after adjustment for confounders. The sample comprised 7994 women, aged 45-64, who participated in the Atherosclerosis Risk in Communities (ARIC) Study. Baseline physical activity was assessed by the Baecke questionnaire. Over an average follow-up of 13.1 yrs, 342 incident breast cancer cases were ascertained. After adjustment for age, race, study center, age at first live birth, age at menopause, and family history of breast cancer in a first-degree relative, there was no statistically significant association of breast cancer incidence with baseline physical activity levels for leisure, sport or work indices. Compared with the lowest quartile of physical activity, women in the highest quartile had a multivariate-adjusted hazard ratio (HR) of 1.00 (95% confidence interval (CI)=0.64-1.54) for the leisure index, 1.31 (95% CI=0.87-1.96) for the sport index and 0.87 (95% CI=0.61-1.24) for the work index. Our findings do not corroborate the majority of previous reports, which implicated physical inactivity as a risk factor for breast cancer.

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