Treosulfan-based conditioning for hematopoietic stem cell transplantation in mucopolysaccharidosis: a pilot study

Treosulfan (Treo), a prodrug of a bifunctional alkylating agent, has been used in conditioning regimens to reduce the risk of hepatic sinusoidal obstruction syndrome. We aimed to establish a Treo-based conditioning regimen for mucopolysaccharidosis (MPS) as a phase 1 study. The regimen included thoracoabdominal irradiation, Treo, fludarabine, and antithymocyte globulin. Antithymocyte globulin was omitted in cord blood transplantation. Five patients with MPS II, aged 8 months to 21 years, were enrolled. Stem cell sources were HLA-C-mismatched unrelated bone marrow in one patient and HLA 1 to 3 allele-mismatched cord blood in four. No patients experienced grade 4 toxicities. Absolute neutrophil count > 500/µL was achieved at a median of 16 days. A pharmacokinetic study showed that AUC_0-12h was 50% higher in children than in adults. Bone marrow donor chimerism at 4 weeks post-transplant was 100% in two patients and 96.7% to 98.1% in three; at 8 weeks, it was 100% in four patients and 77.1% in one who received a reduced dose of Treo. Three patients are alive, but two died at 415 and 767 days post-transplant due to factors unrelated to the conditioning regimen. Treo remains a valuable agent for conditioning regimens in MPS.