Allogeneic Hematopoietic Stem Cell Transplantation For Pesaro Class 3 Thalassemia Major Using Fludarabine-based Conditioning Regimen

Objective To explore the role of Fludarabine (FDR) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for class 3 thalassemia major with regard to regimen toxicity, graft regection,disease recurrence and disease-free survivals (DFS). Methods From June 2001 to October 2004, 8 patients underwent allo-HSCT in our BMT unit, including 5 male and 3 female, with median age 5 (rang 3-19) years. Four patients received allograft from sibling donor, including cord blood and peripheral blood stem cells and the remaining 4 patients received allograft from unrelated donors, including bone marrow and peripheral blood stem cells. Fludarabine was added into the standard BU/CY regimen, consisting of Fludarrabine, busulfan, cyclophosphamide and rabbit anti thymocyte globulin (FDR/BU/CY/ATG). Six patients received myeloablative stem cell transplantation and the remaining 2 patients received nonmyeloablative stem cell transplantation. All patients received Cyclosporine A and short-term Methotrexate for GVHD prophylaxis.Results Eight patients were successfully engrafted with the median time of absolute neutrophil count (ANC) more than 0.5 × 10~9 /L was day +13 (+9~+14) , and the median time of platelet count (PC) more than 20 × 10~9 /L was day +25 (+8~+39). Two patients died of grade IV aGVHD. The regimen-related toxicity occurred in 3 patients. The most frequent manifestation were grade Ⅰ-Ⅱ mucositis , hemorrhagic cystitis , and hepatic toxicity. Of the 8 patients, 6 were disease-free survivals (75%) at a median follow up of 24 (6—36) months. The incidences of grade IV intestine and grade Ⅰ~ Ⅱ skin acute graft-versus-host disease (aGVHD) were 25% and 50% respectively.Conclusion Addition of Fludarabine to the BU/CY conditioning regimen for allogeneic stem cell transplantation in Pesaro III thalassemia major was well tolerated, without increasing toxicity , and associated with durable engraftment and higher rate of disease-free survival (75%). The fludarabine-based conditioning, which is powerfully immunossupressive , has been successfully used for one patient who relapsed following previous allo-BMT and two patients who received nonmyeloablative allogeneic stem cell transplantation from unrelated donors.