Treosulfan‐based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease

Abstract

SummaryAlthough allogeneic haematopoietic stem cell transplantation (HSCT) still represents the only consolidated possibility of cure for sickle cell disease (SCD) patients, its use has been limited by the risk of morbidity and mortality associated with conventional myeloablative therapy. The introduction of treosulfan to replace busulfan in conditioning regimens has recently been explored by virtue of its lower toxicity profile. We report our experience with a treosulfan/thiotepa/fludarabine conditioning for human leucocyte antigen (HLA)-matched sibling or unrelated donor-HSCT in 15 children with SCD, and compare patient outcomes with those of a historical cohort (15 patients) given a busulfan-based regimen. Engraftment was achieved in 28 out of 30 patients (93%), with one case of graft failure in either group. The conditioning regimen was well tolerated in both groups, with no cases of grade III-IV regimen-related toxicity. The 7-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 100% and 93%, respectively, with a 93% DFS in both busulfan and treosulfan groups. No SCD-related adverse events occurred after engraftment in patients with complete or mixed donor chimerism. This retrospective analysis suggests that a treosulfan-based conditioning regimen is able to ensure engraftment with excellent OS/DFS and low regimen-related toxicity in patients with SCD.

A trial of unrelated donor marrow transplantation for children with severe sickle cell disease

“…[48][49][50] Novel preparative agents such as treosulfan and GVHD prophylaxis methods such as posttransplant cyclophosphamide have shown recent promise in transplantation for SCD. 51,52 HRQL improved significantly by 1 year posttransplant in the areas of Change in Health for these patients compared with pretransplant scores. Other HRQL domains did not show significant changes from baseline.…”

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

“…25 Efforts to decrease the early and late complications of transplantation attributed to conditioning regimens have led to RIC regimens. Flu, treosulfan, melphalan, and low-dose TBI 24,[34][35][36] have all been shown to decrease toxicity from the regimen per se, but the risk for rejection is higher. 16 Others have used regimens with minimal toxicity, but that has required prolonged immune suppression to sustain engraftment.…”

Penetration of Treosulfan and its Active Monoepoxide Transformation Product into Central Nervous System of Juvenile and Young Adult Rats

“…In the last decade the anticancer drug treosulfan (TREO) has emerged as a promising myeloablative agent used before hematopoietic stem cell transplantation (HSCT) in pediatric and adult patients (Główka et al, 2010;Nemecek et al, 2011;Slatter et al, 2011;Wachowiak et al, 2011;Casper et al, 2012;Shimoni et al, 2012;Beier et al, 2013;Dinur-Schejter et al, 2015;Boztug et al, 2015;Lawitschka et al, 2015;Strocchio et al, 2015). Currently, various clinical phase II and one phase III trials are conducted aimed at the registration of the myeloablative conditioning agent.…”