Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan

The occurrence of late sequelae after myeloablative conditioning regimens for stem-cell transplantation (SCT) has prompted the introduction of reduced-intensity chemotherapy (RIC) regimens in an attempt to reduce toxicity and spare fertility. We retrospectively evaluated gonadal function in survivors of SCT in childhood by comparing patients conditioned with a myeloablative regimen containing busulfan and cyclophosphamide (BuCy, N=51, 28 boys) and a RIC regimen containing fludarabine and melphalan (FluMel, N=40, 19 boys). Spontaneous puberty occurred in 56% of girls and 89% of boys after BuCy, whereas 90% of females and all males in the FluMel group entered puberty spontaneously (P=0012). Significantly more females (61%) conditioned with BuCy required hormone replacement compared with the FluMel group (105%, P=0012). Females in the FluMel group took significantly longer to develop elevation of serum follicle-stimulating hormone (FSH) concentrations (>10iu/l) from the onset of puberty than females in the BuCy group (median 52years vs. 27years respectively, P=00135). In males no difference was noted between the two conditioning groups in time to FSH elevation (median 4years in FluMel versus 6years in BuCy). Whilst the two regimens have similar effects on the testis, ovarian function seems to be better preserved in females undergoing SCT with RIC.