GONADAL-FUNCTION AFTER BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIADURING CHILDHOOD

Objective: To examine the impact of bone marrow transplantation (BMT), using high-dose chemotherapy and hyperfractionated total body irradia tion, on gonadal function in survivors of acute leukemia treated durin g childhood. Study design: We conducted a retrospective study of 33 su bjects (17 boys) who underwent a BMT for acute leukemia (acute lymphob lastic leukemia, n = 20; acute myelogenous leukemia, n = 13) at a sing le institution. All patients were prepubertal at the time of BMT (medi an age, 7.1 years (3.7 to 11.6 years)); at the time of their last exam ination the boys were a median of 14 years (10.4 to 17.1 years) of age and the girls were a median of 16.9 years (9.5 to 21.9 years) of age. Results: Of 17 boys, 14 (82%) entered puberty spontaneously and 13 de monstrated age-appropriate plasma concentrations of testosterone. Two boys (aged 10.5 and 11 years) remain clinically and hormonally prepube rtal, and one boy has overt Leydig cell failure requiring androgen rep lacement therapy. Thirty-six percent of pubertal boys have elevated pl asma concentrations of luteinizing hormone and 64% have raised levels of follicle-stimulating hormone. Boys with increased levels of luteini zing hormone were significantly younger at BMT (5.4 +/- 0.8 vs 7.8 +/- 0.8 years; p = 0.024). Of 16 girls, 9 (56%) had spontaneous puberty w ith onset of menarche at a median age of 13 years (9.5 to 15.8 years). Though six (67%) of these nine girls have had increased plasma concen trations of luteinizing and follicle-stimulating hormones, normalizati on has occurred in two during a period of 4 to 7 years. The remaining seven subjects required hormone replacement because of clinical and bi ochemical evidence of ovarian failure. One of these subjects has recov ered ovarian function after 51/2 years. Female patients with ovarian f ailure were significantly older at BMT compared with female patients w ith spontaneous puberty/menarche (8.6 +/- 23 years vs 6.1 +/- 1.8; p = 0.03). Conclusion: Our results indicate that most prepubertal boys un dergoing BMT with chemotherapy and hyperfractionated total body irradi ation can expect to enter and progress normally through puberty. For p repubertal girls treated with these regimens, at least 50% retain adeq uate ovarian function to enter puberty and menstruate regularly.