Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using Novel Conditioning Regimen

Abstract Patients with severe thalassemia (Thal) commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haplo-identical related donors, we introduced a program consisting of a pharmacological pretransplant immune suppression phase (PTIS), two courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-IV Busulfan and post-transplant graft-vs-host disease prophylaxis with cyclophosphamide, Tacrolimus and mycophenolate mofetil. We transplanted 83 consecutive transfusion dependent thalassemia patients (median age 12 years, range 1-28 years) with a minimum follow-up of six months (median 15 months, range 7-53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients we had two graft failures, both of them occurring in patients with extremely high titers of anti-donor specific HLA antibodies (anti-DSA), but after adjusting the PTIS to include bortezomib and Rituximab for patients with high titers of anti-DSA, and using pharmacological dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude, that this is a safe and efficacious approach to allogeneic SCT in Thalassemia, yielding results comparable to those available for patients with fully matched donors.