Transplantation of highly purified CD34⁺ progenitor cells from alternative donors in children with refractory severe aplastic anaemia

Abstract

Summary Without transplantation from a human leucocyte antigen‐identical family donor, refractory severe aplastic anaemia (SAA) has an unfavourable prognosis. Conventional transplantation from a matched unrelated donor carries a high rate of mortality. We transplanted large numbers of highly purified CD34+ cells from matched unrelated (n = 4), mismatched unrelated (n = 4) and mismatched related (n = 1) donors into nine children with refractory SAA. The grafts consisted of granulocyte colony‐stimulating factor‐mobilized peripheral positively selected CD34+ cells. A median of 15·1 × 106/kg CD34+ stem cells and 11 × 103/kg CD3+ T‐lymphocytes were infused. No additional pharmacological graft versus host disease (GVHD) prophylaxis was given. At a median follow‐up of 47 (range 37–72) months, eight patients (89%) were in complete remission with >90% donor chimaerism and no evidence of GVHD. One patient died on day +238 as a consequence of GVHD. The use of highly purified mobilized CD34+ stem cells warrants further clinical exploration in children with refractory SAA.

Recent improvement in outcome of unrelated donor transplantation for aplastic anemia

“…25 Other studies have reported outcome in patients with SAA transplanted from donors other than HLA-identical siblings using registry data, with survival probabilities of approximately 35%. 11 Some series have reported better results, 19,[26][27][28][29][30][31][32] for example, in a recent Japanese study of 154 patients showing overall survival of 56%. 26 Donorrecipient HLA disparity was determined using highresolution techniques, but donor-recipient compatibility was not a significant factor in this study.…”

Risk-adapted procedures for HSCT from alternative donor in children with severe aplastic anaemia

“…16,17 Conditioning regimen There are only a few publications on childhood alternative donor transplants in SAA, and most cohorts are very small. Kojima et al 18 reported on 15 children grafted with unmanipulated marrow from serologically matched unrelated donor after conditioning with CY, anti-thymocyte globulin and TBI 5 Gy.…”

Making Therapeutic Decisions in Adults with Aplastic Anemia

“…19 Other approaches have been to use alemtuzumab instead of ATG in an otherwise similar regimen to EBMT, 25 or G-CSF-mobilized CD34 + -selected PBSC. 26 However, both these latter approaches require further evaluation in larger studies.…”