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Will a reduced-toxicity conditioning regimen improve the results of stem cell transplantation in metabolic disease?

Bone Marrow Transplantation volume 37, page 615 (2006)Cite this article

Escolar et al.1 have reported that early transplantation of asymptomatic newborns affected by Krabbe's disease favorably alters the course of the disease. Twenty-five newborns and infants underwent an unrelated cord blood transplantation after a standard myeloablative conditioning regimen with busulphan and cyclophoshamide and the survival was significantly better among asymptomatic newborns than symptomatic infants or untreated controls.

The use of myeloablative doses of busulphan has been routinely adopted in stem cell transplantation for many years but its significant extra-hematological toxicity on liver, central nervous system, lung and bladder2, 3 raises some concerns on its use when these organs are already damaged or defective before transplantation. In Escolar's study, seven of 11 asymptomatic newborns with Krabbe's disease had signs of dysmyelination on the baseline pretransplantation magnetic resonance imaging; moreover, an abnormal concentration of protein in the cerebrospinal fluid was detected in seven of nine newborns evaluated. In patients transplanted for a congenital neurodegenerative disease, it is preferable to avoid the brain being exposed to neurotoxic drugs, because the resulting effect on cerebral function is difficult to predict. There are alternative drugs to busulphan that can achieve complete myeloablation with limited extra-hematological toxicity. Treosulphan is a water-soluble alkylating agent with a potent hematopoietic stem cell toxicity, comparable to that of busulphan or total body irradiation, but with few dose-limiting nonhematologic toxicities (mucositis, metabolic acidosis), and a very favorable pharmacokinetic profile (intravenous administration, single day-dose). In combination with potent immunosuppressive drugs, such as cyclophosphamide or fludarabine, or other alkylating drugs (melphalan), treosulphan has been shown to be an effective and well-tolerated myeloablative agent, both in adult and pediatric patients at high risk of regimen-related complications.3, 4, 5, 6

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  1. Department of Pediatrics, Clinic of Pediatric Hematology Oncology, University of Padova, Padova, Italy

    S Cesaro

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Cesaro, S. Will a reduced-toxicity conditioning regimen improve the results of stem cell transplantation in metabolic disease?. Bone Marrow Transplant 37, 615 (2006). https://doi.org/10.1038/sj.bmt.1705275

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