In this issue of , Derderian et al demonstrate that in utero administration of an anti-c-Kit receptor antibody to mice augments engraftment of congenic donor hematopoietic stem cells (HSCs) infused in the neonatal period.
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| http://dx.doi.org/10.1182/blood-2014-06-579680 | DOI Listing |
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Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.
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Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) is proving successful to treat several genetic diseases. HSPCs are mobilized, harvested, genetically corrected ex vivo, and infused, after the administration of toxic myeloablative conditioning to deplete the bone marrow (BM) for the modified cells. We show that mobilizers create an opportunity for seamless engraftment of exogenous cells, which effectively outcompete those mobilized, to repopulate the depleted BM.
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Graft-versus-host disease (GVHD) has remained the main cause of post-transplantation mortality and morbidity after allogeneic hematopoietic cell transplantation (alloHCT), adding significant economic burden and affecting quality of life. It would be desirable to reduce the rate of GVHD among patients in complete remission (CR) without increasing the risk of relapse. In this study, we have tested a novel conditioning regimen of total marrow and lymphoid irradiation (TMLI) at 2000 cGy, together with post-transplantation cyclophosphamide (PTCy) for patients with acute myeloid leukemia in first or second CR, to attenuate the risk of chronic GVHD by using PTCy, while using escalated targeted radiation conditioning before allografting to offset the possible increased risk of relapse.
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In the tyrosine kinase inhibitor (TKI) era, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the most potential approach for cure of adult patients with Philadelphia chromosome-positive acute lymphocytic leukemia (Ph ALL). TKI plus chemotherapy has strikingly increased response rates and depth of response, and facilitated allo-HSCT, which decreases relapse and improves survival eventually. Meanwhile, for those with older age or comorbidities at diagnosis, TKI in combination with reduced-intensity chemotherapy or chemotherapy-free strategy reduces treatment-related mortality, deferred intensive chemotherapy increases molecular responses and reduced-intensity conditioning (RIC) allo-HSCT improves survival finally.
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