Long-term complications after allogeneic hematopoietic stem cell transplantation for pediatric patients with acute leukemia or myelodysplastic syndrome given either a Treosulfan- or a Busulfan-based conditioning regimen: results of an AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) retrospective study

Background: Patients given hematopoietic stem cell transplantation (HSCT) during their childhood for hematological malignancies have an increased risk of developing long-term sequelae that are in part attributable to the conditioning regimen. Objective: The present study aimed to assess the occurrence of long-term toxicities in a population of children undergone to HSCT for hematological malignancies using either Treosulfan or Busulfan in the conditioning regimen. Study design: Cumulative Incidence of growth impairment, alteration of gonadal function, alteration of the thyroid function, cataract, incidence of secondary malignant neoplasia and alteration of pulmonary function were retrospectively evaluated by univariable and multivariable analysis in a population of 521 pediatric patients affected by acute leukemias and myelodysplastic syndromes treated in 20 Italian Transplant Centers affiliated to AIEOP (Associazione Italiana Ematologia ed Oncologia Pediatrica) RESULTS: The median duration of the follow up of the entire study population was of 7,1 years (range 1 -16 years). Overall, patients given Busulfan developed long-term toxicities in a larger proportion of cases compared to patients treated with Treosulfan (34% versus 20% p=0.01). In univariable analysis, patients having received Treosulfan developed gonadal toxicity in 10% (95%CI: 3-15) of the cases compared with 38% (95%CI: 24-39) of Bu-treated patients (p=0,02) and this finding was confirmed by multivariable analysis (Relative Risk: 0,51 95%CI: 0,34-0,76 p=0.0009). For all the other long-term toxicities our study did not show a statistically significant association between their occurrence and the use of either Busulfan or Treosulfan. Conclusions: This study provides evidence that the use of Treosulfan is correlated with a reduced incidence of gonadal toxicity in children undergoing HSCT for hematological malignancies.