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Lentiviral-mediated Knockdown During Ex Vivo Erythropoiesis of Human Hematopoietic Stem Cells
Published on: July 16, 2011
Effects on erythropoiesis of alemtuzumab-containing reduced intensity and standard conditioning regimens
Aleksandar Mijovic1, Atiyeh Abdallah, Laurence Pearce
1Department of Haematological Medicine, King's College Hospital, London, UK. aleksandar.mijovic@kch.nhs.uk
Haemopoietic cell transplantation (HCT) with reduced-intensity conditioning (RIC) has been associated with delayed disappearance of host anti-A and anti-B isohaemaglutinins and hindrance of donor erythropoiesis in major ABO mismatched transplants. Erythroid recovery, disappearance of recipient type and appearance of donor-type isohaemaglutinins was compared in 84 patients undergoing RIC and 50 patients with standard-conditioning (SCo) HCT. All patients received alemtuzumab as part of their conditioning. The incidence of immune-mediated anaemia and red cell transfusion usage were also compared. Immune factors affecting post-transplant erythroid kinetics showed little variance between different conditioning regimens. Disappearance of recipient isohaemaglutinins and emergence of donor red cells proceeded at similar rates in RIC and SCo transplants; the effects of ABO mismatch were marginal. Pure red cell aplasia, alloimmune haemolysis and autoimmune haemolytic anaemia were not more common in RIC transplants. We believe that alemtuzumab played a critical role in dampening immune reactions of both the host and the donor. Patients in both conditioning groups had similar post-transplant erythroid burst-forming unit (BFU-E) counts; BFU-E chimaerism analysis showed that 90-100% progenitors were of donor origin. However, transfusion requirements were significantly higher in the SCo group, due at least partly to earlier onset of bone marrow hypoplasia.
Haemopoietic cell transplantation (HCT) with reduced-intensity conditioning (RIC) has been associated with delayed disappearance of host anti-A and anti-B isohaemaglutinins and hindrance of donor erythropoiesis in major ABO mismatched transplants. Erythroid recovery, disappearance of recipient type and appearance of donor-type isohaemaglutinins was compared in 84 patients undergoing RIC and 50 patients with standard-conditioning (SCo) HCT. All patients received alemtuzumab as part of their conditioning. The incidence of immune-mediated anaemia and red cell transfusion usage were also compared. Immune factors affecting post-transplant erythroid kinetics showed little variance between different conditioning regimens. Disappearance of recipient isohaemaglutinins and emergence of donor red cells proceeded at similar rates in RIC and SCo transplants; the effects of ABO mismatch were marginal. Pure red cell aplasia, alloimmune haemolysis and autoimmune haemolytic anaemia were not more common in RIC transplants. We believe that alemtuzumab played a critical role in dampening immune reactions of both the host and the donor. Patients in both conditioning groups had similar post-transplant erythroid burst-forming unit (BFU-E) counts; BFU-E chimaerism analysis showed that 90-100% progenitors were of donor origin. However, transfusion requirements were significantly higher in the SCo group, due at least partly to earlier onset of bone marrow hypoplasia.
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