TY - JOUR
T1 - Effect of Busulfan and Treosulfan on Gonadal Function after Allogeneic Stem Cell Transplantation in Children and Adolescents with Nonmalignant Diseases Is Not Exposure-Dependent
AU - van der Stoep, M. Y. Eileen C.
AU - Bense, Joëll E.
AU - de Kloet, Liselotte C.
AU - von Asmuth, Erik G. J.
AU - de Pagter, Anne P. J.
AU - Hannema, Sabine E.
AU - Guchelaar, Henk-Jan
AU - Zwaveling, Juliette
AU - Lankester, Arjan C.
N1 - Funding Information: Financial disclosure: This study was supported by Grant 213 from the Dutch Foundation Kinderen Kankervrij (KiKa) . Publisher Copyright: © 2023 The American Society for Transplantation and Cellular Therapy
PY - 2023/8
Y1 - 2023/8
N2 - With an increasing number of young patients surviving into adulthood after hematopoietic stem cell transplantation (HSCT), gonadal dysfunction becomes an important late effect with significant impact on quality of life. In this retrospective study, we evaluated the exposure of busulfan (Bu) and treosulfan (Treo) in relation to gonadal function in pediatric patients who underwent HSCT for a nonmalignant disease between 1997 and 2018. In the Bu group, 56 patients could be evaluated, and gonadal dysfunction was found in 35 (63%). Lower Bu exposure (ie, cumulative area under the curve [AUC] <70 mg*h/L) was not associated with a reduced risk of gonadal dysfunction (odds ratio [OR], .92; 95% confidence interval [CI], .25 to 3.49; P = .90). In the Treo cohort, 32 patients were evaluable and gonadal insufficiency occurred in 9 patients (28%). Lower Treo exposure (AUC <1750 mg*h/L on day 1) was not associated with a reduced risk of gonadal dysfunction (OR, 1.6; 95% CI, .16 to 36.6; P = .71). Our data do not support the premise that reduced-intensity Bu-based conditioning reduces the risk for gonadal toxicity, and it is unlikely that therapeutic drug monitoring-based reduced treosulfan exposure will further limit the risk of gonadal dysfunction.
AB - With an increasing number of young patients surviving into adulthood after hematopoietic stem cell transplantation (HSCT), gonadal dysfunction becomes an important late effect with significant impact on quality of life. In this retrospective study, we evaluated the exposure of busulfan (Bu) and treosulfan (Treo) in relation to gonadal function in pediatric patients who underwent HSCT for a nonmalignant disease between 1997 and 2018. In the Bu group, 56 patients could be evaluated, and gonadal dysfunction was found in 35 (63%). Lower Bu exposure (ie, cumulative area under the curve [AUC] <70 mg*h/L) was not associated with a reduced risk of gonadal dysfunction (odds ratio [OR], .92; 95% confidence interval [CI], .25 to 3.49; P = .90). In the Treo cohort, 32 patients were evaluable and gonadal insufficiency occurred in 9 patients (28%). Lower Treo exposure (AUC <1750 mg*h/L on day 1) was not associated with a reduced risk of gonadal dysfunction (OR, 1.6; 95% CI, .16 to 36.6; P = .71). Our data do not support the premise that reduced-intensity Bu-based conditioning reduces the risk for gonadal toxicity, and it is unlikely that therapeutic drug monitoring-based reduced treosulfan exposure will further limit the risk of gonadal dysfunction.
KW - Busulfan
KW - Conditioning regimen
KW - Late effects
KW - Nonmalignant diseases
KW - Pediatrics
KW - Pharmacokinetics
KW - Treosulfan
UR - http://www.scopus.com/inward/record.url?scp=85161609172&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtct.2023.05.003
DO - https://doi.org/10.1016/j.jtct.2023.05.003
M3 - Article
C2 - 37156421
SN - 2666-6367
VL - 29
SP - 529.e1-529.e5
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 8
ER -