Allogeneic Hematopoietic Stem Cell Transplantation for Pesaro IIIβ-Thalassemia Major Using Fludarabine-Based Myeloablative or Non-Myeloablative Conditioning Regimen.

Objective : To explore the efficacy of Fludarabine-based myeloablative or non-myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for classIII thalassemia major with regard to regimen toxicity, graft rejection, and disease-free survival (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 (3 ~ 19) years. Four patients received graft from sibling donor, including cord blood and peripheral blood stem cells, and the remaining 4 patients received graft from unrelated donors, including bone marrow and peripheral blood stem cells. Fludarabine (FDR) was added into the standard BU/CY regimen, consisting of FDR, BU, CY and ATG. Six patients received myeloablative stem cell transplantation and the remaining 2 patients with evidence of organ damage from iron-overload received nonmyeloablative unrelated donor stem cell transplantation. All patients received Cyclosporine A and Methotrexate for GVHD prophylaxis.

Results: Eight patients were successfully engrafted with the median time of absolute neutrophil count (ANC) more than 0.5 ×10⁹ /L was day +13 (+9 ~ +14), and the median time of platelet count more than 20 ×10⁹ /L was day +25 (+8 ~ +39). Two patients died of grade IV aGVHD. The regimen-related toxicity (gradeImucositis, gradeII hemorrhagic cystitis, and gradeIhepatic toxicity) occurred in 3 patients. At a median follow up of 24 (8~48) months, the probability of DFS was 75%, including the two patients given nonmyeloablative stem cell transplantation from unrelated donor.

Conclusion: Fludarabine-based conditioning regimen for allo-HSCT in Pesaro III thalassemia major was well tolerated, without increasing toxicity, and associated with durable engraftment and higher rate of DFS (75%). The successful transplantation from unrelated donors using nonmyeloablative conditioning showed that thalassemia clone can be eradicated by the reduced intensity HSCT, which relies upon immunosuppressive rather than myeloablative conditioning to facilitate engraftment of donor cells, and is a novel approach for the treatment of the patients with evidence of organ damage from iron-overload.