Gonadal function after bone marrow transplantation for acute leukemia during childhood.
OBJECTIVE
To examine the impact of bone marrow transplantation (BMT), using high-dose chemotherapy and hyperfractionated total body irradiation, on gonadal function in survivors of acute leukemia treated during childhood.


METHODS
We conducted a retrospective study of 33 subjects (17 boys) who underwent a BMT for acute leukemia (acute lymphoblastic leukemia, n = 20; acute myelogenous leukemia, n = 13) at a single institution. All patients were prepubertal at the time of BMT (median age, 7.1 years (3.7 to 11.6 years)); at the time of their last examination 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 demonstrated age-appropriate plasma concentrations of testosterone. Two boys (aged 10.5 and 11 years) remain clinically and hormonally prepubertal, and one boy has overt Leydig cell failure requiring androgen replacement therapy. Thirty-six percent of pubertal boys have elevated plasma concentrations of luteinizing hormone and 64% have raised levels of follicle-stimulating hormone. Boys with increased levels of luteinizing 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 with 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 concentrations of luteinizing and follicle-stimulating hormones, normalization has occurred in two during a period of 4 to 7 years. The remaining seven subjects required hormone replacement because of clinical and biochemical evidence of ovarian failure. One of these subjects has recovered ovarian function after 5 1/2 years. Female patients with ovarian failure were significantly older at BMT compared with female patients with spontaneous puberty/menarche (8.6 +/- 23 years vs 6.1 +/- 1.8; p = 0.03).


CONCLUSIONS
Our results indicate that most prepubertal boys undergoing BMT with chemotherapy and hyperfractionated total body irradiation can expect to enter and progress normally through puberty. For prepubertal girls treated with these regimens, at least 50% retain adequate ovarian function to enter puberty and menstruate regularly.
Sarafoglou
K
K
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Boulad
F
F
Gillio
A
A
Sklar
C
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000503:physiopathology / Q000628:therapy*; D011627:Puberty / Q000187:drug effects / Q000528:radiation effects; D012189:Retrospective Studies; D013737:Testis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects