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    Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia
    (2021) Nagler, Arnon; Kanate, Abraham S.; Labopin, Myriam; Ciceri, Fabio; Angelucci, Emanuele; Koc, Yener; Gulbas, Zafer; Arcese, William; Tischer, Johanna; Pioltelli, Pietro; Ozdogu, Hakan; Afanasyev, Boris; Wu, Depei; Arat, Mutlu; Peric, Zinaida; Giebel, Sebastian; Savani, Bipin; Mohty, Mohamad; 32354866
    Graft-versus-host disease (GvHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation includes posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing data in the European Society for Blood and Marrow Transplantation registry, we compared ATG- versus PTCy-based GvHD prophylaxis in 434 adults with acute lymphoblastic leukemia undergoing haploidentical hematopoietic cell transplantation. Of the 434 patients included in this study, ATG was used in 98 and PTCy in 336.. The median follow-up was approximately 2 years. The baseline characteristics of the patients were similar between the groups except that the ATG group was more likely to have had relapsed/refractory acute lymphoblastic leukemia (P=0.008), had conditioning not including total body irradiation (P<0.001), have had peripheral blood as the source of their grafts (P=0.001) and to have been transplanted in an earlier timeperiod (median year of transplantation: 2011 vs. 2015). The 100-day rates of grade II-IV and III-IV acute GvHD were similar in the ATG and PTCy groups, as were 2-year chronic GvHD rates. On multivariate analysis, leukemia-free survival and overall survival were better with PTCy than with ATG prophylaxis. Relapse incidence was lower in the PTCy group (P=0.03), while non-relapse mortality was not different. Advanced disease and lower performance score were associated with poorer leukemia-free survival and overall survival and advanced disease was associated with inferior GvHD-free/relapse-free survival. Compared to bone marrow grafts, peripheral grafts were associated with higher rates of GvHD. In patients with acute lymphoblastic leukemia undergoing unmanipulated haploidentical hematopoietic cell transplantation, PTCy for GvHD prevention resulted in a lower incidence of relapse and improved leukemia-free survival and overall survival, compared to ATG.
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    A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
    (2019) Song, Yuanbin; Rongvaux, Anthony; Taylor, Ashley; Jiang, Tingting; Tabaldi, Toma; Balasubramanian, Kunthavai; Bagale, Arun; Terzi, Yunus Kasim; Gbyli, Rana; Wang, Xiaman; Fu, Xiaoying; Gao, Yimeng; Zhao, Jun; Podoltsev, Nikolai; Xu, Mina; Neparidze, Natalia; Wong, Elice; Torres, Richard; Bruscia, Emanuela M.; Kluger, Yuval; Manz, Markus G.; Flavell, Richard A.; Halene, Stephanie; 0000-0001-5612-9696; 30664659; B-4372-2018
    Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.