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Conditioning Regimens

Reduced-intensity conditioning for severe aplasia using fludarabine and CY followed by infusion of ex vivo T-cell-depleted grafts leads to excellent engraftment and absence of GVHD

Abstract

We studied the outcome of individuals with aplastic anaemia (AA) who received reduced-intensity conditioning followed by the infusion of stem cell grafts that had been T-cell depleted ex vivo with alemtuzumab. Consecutive patients with AA who had an HLA-identical sibling received conditioning with fludarabine 30 mg/m2 daily for 5 days followed by CY 60 mg/kg on 2 consecutive days. Cytokine-mobilized blood grafts were incubated ex vivo with alemtuzumab ‘in the bag’ and infused without washing. CYA was prescribed until day +90. Engraftment rate, GVHD, EFS and overall survival were studied. Fifteen patients received PBPC grafts. It was the second graft in one of the patients. Ten patients were male and their median age was 23.5 years. The toxicity of the conditioning was minimal. One patient received 1 × 107/kg donor lymphocytes for rising chimerism. At a median of 1107 (294–1778) days, all of them survived with normal blood parameters. None of them developed acute or chronic GVHD. In patients with AA the combination of purine analogue and alkylator leads to rapid engraftment despite T-cell depletion of grafts. This strategy of reduced-intensity conditioning has low toxicity, does not compromise engraftment and seems effective for prevention of GVHD.

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Novitzky, N., Thomas, V., du Toit, C. et al. Reduced-intensity conditioning for severe aplasia using fludarabine and CY followed by infusion of ex vivo T-cell-depleted grafts leads to excellent engraftment and absence of GVHD. Bone Marrow Transplant 43, 779–785 (2009). https://doi.org/10.1038/bmt.2008.390

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