Gonadal Function after Busulfan Compared with Treosulfan in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplant

Abstract

Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre-and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P = .02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P = .03 and P = .04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

“…In a registry analysis of HCT-CI in nonmalignant diseases, HCT-CI scores 3 were associated with a significant decrease in survival [43] and, because severe combined immunodeficiency represented nearly half of PID patients in that study, the extent of comorbidities seen in older patients with PIDs requiring BMT was almost certainly underrepresented. Although reduced-toxicity, treosulfan-containing MAC regimens for PID have yielded very good outcomes, treosulfan is not available worldwide, rates of long-term toxicities such as infertility are not well defined, and SOS risk is not eliminated [44][45][46][47][48][49][50]. Additionally, underlying liver pathology may not always be identified pre-BMT, potentially making this patient population more vulnerable to SOS.…”

Long Term Outcome and Immune Function After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency

“…Two adults transplanted for chronic granulomatous disease were reported as fathering children after receiving a targeted dose regimen of busulfan with fludarabine (5). A recent study of the European Society for Blood and Marrow Transplantation suggests that gonadal damage may be less following treosulfan-based conditioning compared to busulfan-based conditioning, although the number of patients receiving treosulfan was much smaller (55). Although these data are few, they suggest that infertility is not inevitable following conditioned HSCT for PID, and that the outlook may be considerably better than previously feared.…”

Urogenital Abnormalities in Adenosine Deaminase Deficiency

“…Recently, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation has established recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who undergo life-saving allogeneic SCT [12]. Emerging reports describe fertility and gonadal function in transplanted SCID [13][14][15], but actually, no specific studies on ADA-SCID have been performed. We recommend that these aspects deserve special attention considering the systemic manifestations of the condition (ADA-SCID) and the potential effects of its treatments on gonadal function.…”