Longitudinal gonadal function after bone marrow transplantation for acute lymphoblastic leukemia during childhood

Abstract

Total body irradiation and high-dose chemotherapy, applied as a preparatory regimen for bone marrow transplantation (BMT) in children with acute lymphoblastic leukemia (ALL), are particularly hazardous to the gonads and, in addition, can impair hypothalamo pituitary-gonadal control. Longitudinal data on pubertal development and gonadal function in these patients are limited. Twenty-one ALL patients (15 males, 6 females) who had successfully undergone allogeneic BMT before puberty (age at BMT: 3.4-12.3 yr) were followed up in University Children's Hospital, Tübingen, Germany over 2 (minimum) to 14 (maximum) years. Tanner development scores, serum testosterone and estradiol, basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were analyzed. During pubertal age, the levels of FSH and LH rose consecutively, resulting in noticeably elevated serum concentrations in 100% and 89%, respectively, of boys older than 14 years and in 75% and 75%, respectively, of girls older than 13 years. Nevertheless, pubertal development has been normal in all patients except in one boy and two girls who required substitution with sexual steroids, as timely puberty (i.e. boys < 14 years, girls < 13 years) did not start. In males with normal puberty, testosterone levels, however, were found to be low-normal. In conclusion, after BMT preceded by total body irradiation for childhood ALL, gonadal function is impaired. Even if normal pubertal development occurs, deficiencies in long-term endocrine function cannot be ruled out. In view of the high FSH levels, the prognosis for fertility is doubtful.