Abstract
We describe the clinical, immunological and molecular characteristics of a 39 yrs-old male with 8 yrs story of paroxysmal nocturnal hemoglobinuria (PNH) who underwent a reduced intensity conditioning bone marrow transplantation (RIC-BMT) from identical sibling donor. The patient was pancytopenic, transfusion-dependent and had suffered from Budd-Chiari syndrome. We already reported that that RIC-BMT restored clonogenic erythroid activity and cytokine production (IL-2, IFN-gamma and TNF-alpha) in BM. Likewise, IL-2, TNF-alpha and TGF-beta formerly increased in both BM and peripheral blood (PB), became normal after BMT. Finally, the PNH clone was no more detectable in both BM and PB cells by molecular analysis 1 year after RIC-BMT. At 2 years after the transplant the patient is well, with Hb levels of 15.2 g/dL, but with low WBC (2.7x109/L) and platelets (71x109/L). The number of CFU-GM and BFU-E in BM further increased and none of the CFU-GM and BFU-E showed the original PIG-A gene mutation. Likewise, none of the PB granulocytes showed the original PIG-A gene mutation also 2 years after BMT. These immunological, molecular and cytokine changes observed 2 years after RIC-BMT support the curative action of a donor immune-mediated “graft versus PNH” effect.
Patient before BMT 1mo after BMT 6mo after BMT 12mo after BMT 24mo after BMT Controls (mean±SE) CFU-GM 7 10 7 10 13 21±9 BFU-E 12 23 46 108 115 62±18
Bone marrow transplantation for paroxysmal nocturnal haemoglobinuria