High Engraftment Rate after Second Stem Cell Transplantation for Thalassemia: A Prospective Study.

Unlike hematological malignancies patients with thalassemia have an increased risk of graft failure or rejection occurring in up to 15% of patients after myeloablative stem cell transplantation from HLA identical related donors. Patients who reject their grafts and have a return of thalassemic hematopoiesis could benefit from second transplantation with the prospect of cure. Our previous experiences of second SCT using BUCY conditioning regimen alone or in combination with antilymphocyte globulin or total lymphoid irradiation showed a higher graft failure rates (43% to 69%). In 2003 we devised a new preparative regimen in an attempt to improve engraftment rate after second transplantation for thalassemia. The treatment protocol (Protocol 26.1) consisted of pre-conditioning immunosuppression-cytoreduction with hydroxiurea 30 mg/kg/day, azathioprine 3 mg/kg/day (day -45 to -12) and fludarabine 30 mg/m2/day (day -17 to -13) and conditioning regimen with BU 14/16 TT10 CY200 ATG (Thymoglobulin)12,5/10. Thirteen patients with median age of 9 years (range, 4–20 years) were given a second SCT according to this protocol. The median time between the first and second transplant was 29 months (range, 8–204 months). As a stem cell source 4 patients received bone marrow and 9 patients unmanipulated peripheral blood stem cells (PBSC). All but two patients received stem cells from the same donor. Twelve out of 13 patients (92%) had sustained full donor engraftment. One patient had early graft failure and died from cerebral bleeding due to refractory thrombocytopenia despite an autologous back-up. Other two patients died from acute or chronic GvHD -related complications. The probability of survival, thalassemia-free survival, transplant related mortality and rejection were 76%, 76%, 18% and 8% respectively with a median follow-up of 26 months (range, 8–47 months). Four patients developed grade II–III and 1 patient grade IV acute GvHD responsive to steroids and 3 patients had extensive chronic GvHD. Both acute and chronic GvHD occurred in patients who received PBSC. The incidence of CMV and EBV reactivation was 62% and 38% respectively. None of these patients developed EBV related lymphoproliferative disorders. Six patients had BK virus- related hemorragic cystitis (2 moderate, 2 severe and 2 mild cystitis). In conclusion, the high engraftment rate observed in this study suggests that this new preparative regimen is effective curative treatment for second transplant in patients with thalassemia. Disclosure: No relevant conflicts of interest to declare.