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- W2114804501 abstract "Allogeneic stem-cell transplant (SCT) is a potentially curative therapy for a variety of hematological malignancies. However, only about 70% of SCT candidates have a human leukocyte antigen (HLA)-matched sibling or a fully matched unrelated donor available, depending on ethnic background. Th e rest rely on an alternative stem-cell source such as a mismatched unrelated donor, umbilical cord blood or a haploidentical related donor [1]. Early trials of haploidentical transplants have failed due to unacceptably high rates of graft failure, graft-versus-host disease (GVHD) and non-relapse mortality (NRM) [2]. An intense bi-directional allogeneic response is exerted by a relatively high frequency of T-cells that recognize major HLA disparities between donors and recipients. Th e breakthrough came from a series of clinical trials in Perugia, Italy [3]. GVHD was almost completely prevented by extensive T-cell depletion of the donor graft, using CD34 � positive selection, and reducing the infused T-cell dose to less than 2 � 10 4 /kg, with no need for additional post-transplant pharmacological immune suppression. Th e HLA barrier to engraftment was crossed by using an intensive conditioning regimen and infusion of a mega-dose ( � 10 � 10 6 /kg) CD34 � cell-containing graft. Th e high numbers of CD34 � cells possessed a veto eff ect against host anti-donor cytotoxic T-cells surviving the conditioning regimen, and constant engraftment was achieved. T-cell depletion is often associated with increased relapse rates after transplant due to loss of the graft-versusleukemia (GVL) eff ect. However, in the HLA-mismatched setting, natural-killer (NK) cells can provide a strong antileukemia eff ect in the absence of GVHD. Selecting a donor with predicted NK alloreactivity in the donor-versus-host direction is feasible in a large proportion of transplants, allowing control of relapse. Th e major remaining obstacle to this extensively T-cell depleted mega-dose CD34 � approach is a very slow immune reconstitution after transplant, resulting in high rates of opportunistic infections such as viral (e.g. cytomegalovirus [CMV]) and fungal infections, resulting in high NRM. Clearly, enhancing immune reconstitution is the major challenge for improving outcomes after haploidentical SCT. Several approaches have been made attempting to accelerate immune reconstitution [4]. One approach is" @default.
- W2114804501 created "2016-06-24" @default.
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- W2114804501 date "2013-07-10" @default.
- W2114804501 modified "2023-09-25" @default.
- W2114804501 title "Haploidentical stem-cell transplant: the challenge of immune reconstitution" @default.
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- W2114804501 doi "https://doi.org/10.3109/10428194.2013.814129" @default.
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