Factors affecting gonadal function after bone marrow transplantation during childhood

Abstract

Summary:Conditioning for bone marrow transplantation (BMT) may alter viability of germ cells and production of gonadal hormones. We analyzed the risk factors for gonadal failure after 12 Gy total body irradiation (TBI) given as six fractions (n = 31, group 1), 10 Gy (one dose) TBI (n = 20, group 2), 6 Gy (one dose) total lymphoid irradiation (TLI, n = 17, group 3) and chemotherapy alone (n = 7, group 4), given at 7.7 ± 0.4 (0.6-13.6) years. Among the 34 girls, seven (20.6%) had normal ovarian function with regular spontaneous menstruation and normal plasma follicle-stimulating (FSH) and luteinizing (LH) hormones, five (14.7%) had partial ovarian failure with regular menstruation but increased FSH and/or LH, and 22 (64.7%) had complete ovarian failure. The 24 girls with chronological and bone ages Ͼ13 years included similar percentages, with increased FSH or LH in all four groups. There was a positive correlation between age at BMT and FSH (r = 0.54, P Ͻ 0.01), but not with LH, and between FSH and LH (r = 0.8, P = 0.0003). Plasma FSH concentrations had returned to normal spontaneously in six cases, and those of LH in two cases. Among the 41 boys, 16 (39%) had normal testicular function and 25 (61%) had tubular failure and increased FSH. Of these, 10 also had Leydig cell failure (three complete and seven partial). The 18 boys with chronological and bone ages Ͼ15 years included similar percentages with increased FSH or LH in groups 1 to 3, and testicular volume was significantly lower in group 2 than in group 3 (P = 0.008). There was no correlation between age at BMT and FSH, LH or testosterone, but there was a negative correlation between FSH and inhibin B (rho = −0.87, P Ͻ 0.003). We conclude that girls are more likely to suffer ovarian failure the older they are at BMT, and that early ovarian recovery is possible. Keywords: bone marrow transplantation; fertility; inhibin; irradiation; ovary; testis Conditioning for bone marrow transplantation (BMT) may alter the production of gonadal hormones (estradiol and progesterone in girls, testosterone in boys) and the viability of germ cells. 1-3 Gonadal failure results in incomplete sexual development and growth at puberty, and sterility in adulthood. Gonadal hormones are required for the development of secondary sexual characteristics, and for the growth acceleration which normally occurs at puberty.The risk factors for gonadal failure in patients undergoing BMT are difficult to analyze because of the variety of conditioning regimens used, and the possibility of gonadal recovery. 4 This study analyzes the expression and frequency of gonadal failure in both sexes according to the conditioning protocol, and the significance of the age during childhood at which BMT is carried out. We also measured plasma inhibin B concentrations as an additional marker of tubular function in these young patients where semen analysis is not possible. PatientsThe gonadal function of 75 patients (34 girls and 41 boys) who received a BMT during childhood, and who were aged more than 10 years ...

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…50,51 For children undergoing allogeneic transplantation the same TBI-related side effects are expected as in the autologous setting, but amplified by immunological complications, that is GVHD and infections because of highly impaired immune reconstitution, which are expected to increase treatment-related mortality and long-term side effects. 50,54,[58][59][60][61] An allogeneic approach could be adopted for children who experience relapse after autologous transplant, such as the eight patients in this series, of whom four were rescued and are in long-term CR3.…”

“…Infertility and an increased incidence of endocrinological problems, growth impairment, early cataracts and second malignancies are expected compared with chemotherapy-treated children. [43][44][45][46]54,[58][59][60] It is always difficult to counterbalance the advantage of higher efficacy with the draw backs of long-term toxicity. Lower complication rates are expected for non-transplanted children, even though their treatment invariably includes cranial irradiation, which also increases the risk of brain tumors, and testicular irradiation or orchiectomy, in the event of testicular relapse.…”

Quality of life, reproduction and sexuality after stem cell transplantation with partially T-cell-depleted grafts and after conditioning with a regimen including total body irradiation

“…These results are in accordance with other studies. [13][14][15][16] Mertens et al 13 showed evidence of gonadal dysfunction in 92% of the male patients and 99% of the female patients. Raised FSH levels in men represent damage to the Sertoli cells, which assist spermatogenesis, and normal LH and testosterone levels are due to the maintenance of Leydig cell function.…”

Seqüelas endócrinas da radioterapia no tratamento do câncer na infância e adolescência

“…Quase 100% das pacientes que têm mais de 10 anos no momento da TBI e 50% daquelas abaixo desta faixa etária irão desenvolver FOP. Algumas pacientes deste grupo podem recuperar a função gonadal com restauração dos níveis de LH, FSH e estradiol a valores normais e menstruação espontânea (36). Comprometimento testicular: pequenas doses de irradiação são capazes de provocar acentuado comprometimento da função testicular.…”

“…Comprometimento testicular: pequenas doses de irradiação são capazes de provocar acentuado comprometimento da função testicular. As células de Leydig são mais resistentes à radioterapia que o epitélio germinativo, sendo a insuficiência androgênica incomum (36). Entretanto, a falência compensada (níveis elevados de LH e normais de testosterona) não é infreqüente.…”