Treosulfan: reduced toxicity conditioning for allogeneic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndrome

Allogeneic hematopoetic stem-cell transplantation (SCT) is a curative treatment for a variety of hematological malignancies. There is a continuous search for novel conditioning regimens that will reduce SCT-related toxicity while retaining maximal anti-malignancy effect. Treosulfan (Treo) was initially used in the treatment of certain solid tumors. Preclinical studies showed that in contrast to Busulfan it has an effect on both committed and non- committed hematopoietic stem cells. It also has stronger immunosuppressive characteristics that make it suitable for conditioning regimens for allogeneic SCT including from cord blood and Haploidentical donors. Treo is also associated with a favorable toxicity profile with little extra-medullary toxicity. The combination of Fludarabine (Flu) and Treo was explored in several studies in patients not eligible for standard myeloablative conditioning, and data are rapidly emerging. The Flu/Treo regimen is associated with consistent engraftment, limited non-relapse mortality, low rates of organ toxicity as well as acute and chronic graft versus host disease (GVHD). The regimen was also associated with low relapse rates of 5-30% depending on disease status at SCT. All together resulted in favorable survival of 40-80%. Promising results were seen mainly in myelodysplastic syndrome (survival of 36-70%) and myeloid leukemia in remission (60-70%). Randomized prospective studies will be needed to better define the role of Treosulfanbased regimens in SCT.