Endocrine Abstracts (2011) 27 P40

Gonadal failure in children with acute lymphoblastic leukaemia treated by bone marrow transplantation: prevalence and risk factors

Huda Burrani1, M Guftar Shaikh2, Anna Maria Ewins2, Brenda Gibson2 & Malcolm Donaldson1

1Glasgow University, Glasgow, UK; 2Royal Hospital for Sick Children, Glasgow, UK.

Background: Gonadal failure is a well-recognized long-term complication of bone marrow transplantation (BMT) in children with acute lymphoblastic leukemia (ALL). Identifying key risk factors is helpful in planning and counselling for hormone replacement therapy (HRT) and in targeting future research.

Objectives: To determine the prevalence and risk factors for primary gonadal failure (PGF) in childhood ALL treated with BMT in a single centre.

Methods and patients: Retrospective study of 108 patients treated from 1989-2009. Of 54 survivors, 40 (25 M and 15 F) aged 22.6 (11–32) years were analysed after excluding patients with insufficient data (4) or BMT carried out <2 years previously (10). BMT was performed at 9.4 (range 2.3–17.3) years, using high-dose chemotherapy with alkylating agents, mainly cyclophosphamide, and total body irradiation (1440 cGy in eight fractions). PGF was defined as basal FSH and LH >10 IU/l in pre-pubertal; FSH >16 and LH >18 IU/l in post-pubertal patients.

Results: The overall prevalence of PGF was 83%. All females were affected irrespective of pubertal status at the time of BMT (eight prepubertal, seven pubertal/postpubertal). 18/25 (72%) males were affected, 11/17 prepubertal, 7/8 pubertal/post pubertal. In females, both FSH and LH levels began rising 6 months post-BMT at 11.7±3.6 years reaching a peak of 58.1±52.6 (1–155) and 26.7±21.8 (0.1–68.2). In males FSH elevation began 3 years post-BMT at 14.2 (10.1–19.4) years to a peak of 22 IU/l (0.3–76.9); LH rose after 5 years at 16.9 (14.8–19.8) years to reach 24.3 IU/l (20.2–32.4) All 15 females but only five males required HRT aged 15.7±2.5 (12–20.8) years.

Conclusion: There is a high prevalence of PGF in paediatric ALL requiring BMT. The increased risk in all females and in pubertal/postpubertal males may be explained by limited follicular reserve in girls and increased Sertoli/Leydig cell vulnerability in older boys.

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