Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may de monstrate hemolysis or venous thrombosis, and may develop MDS or aplastic a nemia. Successful results may be obtained after conditioning and transplant ation from syngeneic or genotypically matched sibling donors. Experience wi th transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent su ccessful MUD BMT for PNH, All three patients had severe aplastic anemia (SA A) and PNH at the time of BMT, Unrelated donors were six-antigen HLA-matche d (n = 2) or HLA-A mismatched (n = 1), Conditioning consisted of cytarabine , cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/C D8 antibodies + complement. Further GVHD prophylaxis consisted of cyclospor ine, Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10( 6) CD34(+) cells/kg, Neutrophil engraftment occurred at 16-21 days, One pat ient developed grade 1 acute GVHD, Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.