Peer-reviewed article
Treosulfan-based conditioning for hematopoietic stem cell transplantation in mucopolysaccharidosis: a pilot study.
Koike T, Kato S, Morimoto T, Yabe H ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a medical study about a conditioning regimen used before stem cell transplantation in children with mucopolysaccharidosis, a rare genetic disorder. The study tested treosulfan combined with other drugs and radiation in five young patients. The treatment was tolerated well with no severe toxicities, and patients achieved good stem cell engraftment, though two died later from unrelated causes.
Key points
- Five children with MPS II received treosulfan-based conditioning for hematopoietic stem cell transplantation
- No grade 4 toxicities were observed
- Neutrophil recovery occurred at median 16 days post-transplant
- Bone marrow chimerism was 96.7% to 100% at 4-8 weeks post-transplant
- Three patients survived; two deaths occurred at 415 and 767 days post-transplant from unrelated causes
Limitations
This is a very small pilot study of only five patients with a rare disease, so results may not be generalizable. The short follow-up period and small sample size limit conclusions about long-term safety and efficacy of this conditioning regimen.
Abstract
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 AUC0-12h 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.