Frequent HLA-DR loss on hematopoietic stem progenitor cells in patients with cyclosporine-dependent aplastic anemia carrying HLA-DR15

The Benign Clone Causing Aplastic Anaemia

“…Laboratory data have shown increased interferon-producing T cells, in the marrow of AA patients. More recently, the "escape mechanisms of stem cells from an autoimmune T cells attack" has been strongly suggested by the following results in AA patients: loss of heterozygosity of chromosome arm 6p [26], loss of HLA DR 15 [27], and structural homology of HLA evolutionary divergence, defining patterns of autoreactivity [26]. This in vitro evidence further supports the autoimmune pathogenesis already suggested to explain the expansion of GPI negative cells.…”

“…In a retrospective analysis, published in 1994 [32], second HCT for graft rejection had a poor outcome of 33%, but appeared to improve in another retrospective report in 2015 [33]. In general, SAA response to treatment is dependent on the age of the patient and the severity of the disease [26]. Haematopietic stem cell transplants (HSCT) from a matched sibling donor is currently the gold standard for SAA patients < 50 years of age.…”

“…In older patients (>30 years), a combination of fludarabine, cyclophosphamide with ATG or alemtuzumab (CAMPATH) is recommended, with a reduction in the cyclophosphamide dose to alleviate toxicity. There is no doubt that bone marrow, rather than mobilised-peripheral blood, is the stem cell source of choice [26]. In the absence of an HLA matched sibling donor, the use of a fully matched-unrelated donor transplant has been shown to be successful [26].…”

“…There is no doubt that bone marrow, rather than mobilised-peripheral blood, is the stem cell source of choice [26]. In the absence of an HLA matched sibling donor, the use of a fully matched-unrelated donor transplant has been shown to be successful [26]. Haploidentical transplantation is now associated with excellent results; however, the use of irradiation in some conditioning regimens is somewhat disconcerting in view of the earlier finding of secondary malignancies in patients with aplastic anaemia, who received irradiation as part of their conditioning [35].…”