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  • Title: Conditioning with purine analogs leads to good engraftment rates of immunodepleted grafts for aplastic anemia.
    Author: Novitzky N, Thomas V, du Toit C.
    Journal: Biol Blood Marrow Transplant; 2013 Apr; 19(4):584-8. PubMed ID: 23270985.
    Abstract:
    Immunodepletion with alemtuzumab is an effective strategy for preventing graft-versus-host disease after allogeneic stem cell transplantation (SCT), but it may be associated with graft failure. We tested the effectiveness of a purine analog-based reduced-intensity conditioning combination in patients undergoing allogeneic SCT for bone marrow aplasia. Patients with severe marrow aplasia who had a tissue-compatible sibling donor were conditioned with fludarabine 30 mg/m(2) for 5 days and cyclophosphamide 120 mg/kg. Stem cells from HLA-identical sibling donors were mobilized with filgrastim, and the harvested blood concentrates were incubated ex vivo with alemtuzumab. After graft infusion, patients received therapeutic doses of cyclosporine up to day 90. The primary objective of this study was to examine the proportion of patients who achieved engraftment and overall survival. Secondary objectives were the rates of graft-versus-host disease, posttransplantation infections, and graft failure. The study group comprised 30 patients who received a total of 31 cytokine-mobilized blood stem cell transplantations. The median CD34(+) cell dose infused was 4.99 × 10(6)/kg. All patients engrafted at a median of 12 days post-SCT. Two patients exhibited delayed graft failure, at 3 months and 7 months post-SCT, and required retransplantation or donor lymphocyte infusion to reestablish full-donor chimerism. At a median of 1,560 days post-SCT, all patients survived and were transfusion-free. We confirm that the combination of purine analog and cyclophosphamide is adequate for engraftment of grafts immunodepleted with alemtuzumab. This strategy is associated with excellent outcomes.
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