Early alternative donor HSCT is a potentially curative therapeutic option for patients with AAA not responding to IST. Seven patients (median age at diagnosis, 11 yr) with refractory AAA without a MSD underwent HSCT from matched unrelated (n = 6) or haploidentical (n = 1) donors. Conditioning regimens included CY (n = 7), muromonab-CD3/ATG (n = 7), TT (n = 6), FLU (n = 5), and TLI (n = 2). Grafts were either CD34 purified and/or CD3/19 depleted and contained a median of 10.17 × 10(6) /kg CD34 and 5.5 × 10(4) /kg CD3 cells. All patients engrafted rapidly. Median time to leukocyte engraftment was 10 days. With a median follow-up of 26 (range, 11-153) months, six patients are alive and well with complete donor hematopoiesis. One heavily pretreated patient developed GVHD grade III and died from progressive renal failure (resulting from microangiopathic hemolytic anemia) and disseminated aspergillosis. Early alternative donor HSCT can help to avoid complications from prolonged IST and presumably improve survival of patients with refractory AAA. Administration of high doses of CD34 purified and/or CD3/19 depleted stem cells following novel immunoablative conditioning may prevent graft rejection and GVHD. However, a long interval from diagnosis to HSCT seems to be associated with poor outcome.

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