Association of Disparities in Known Minor Histocompatibility Antigens with Relapse-Free Survival and Graft-versus-Host Disease after Allogeneic Stem Cell.

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Association of Disparities in Known Minor Histocompatibility Antigens with Relapse-Free Survival and Graft-versus-Host Disease after Allogeneic Stem Cell.

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Association of Disparities in Known Minor Histocompatibility Antigens with Relapse-Free Survival and Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Willemijn Hobo, Kelly Broen, Walter J.F.M. van der Velden, Annelies Greupink-Draaisma, Niken Adisty, Yannick Wouters, Michel Kester, Hanny Fredrix, Joop H. Jansen, Bert van der Reijden, J.H. Frederik Falkenburg, Theo de Witte, Frank Preijers, Ton Schattenberg, Ton Feuth, Nicole M. Blijlevens, Nicolaas Schaap, Harry Dolstra Biology of Blood and Marrow Transplantation Volume 19, Issue 2, Pages 274-282 (February 2013) DOI: 10.1016/j.bbmt.2012.09.008 Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Clinical outcome parameters after partially T cell–depleted allo-SCT in the complete cohort of allo-SCT recipients. OS (A), RFS (B), and cumulative incidence of NRM (C) were determined by Kaplan-Meier analysis. Biology of Blood and Marrow Transplantation 2013 19, 274-282DOI: (10.1016/j.bbmt.2012.09.008) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Occurrence of GVHD after MiHA-mismatched allo-SCT. In the complete cohort, the incidence rates of aGVHD grade III-IV (A) and limited/extensive cGVHD (B) were determined using Fine-Gray competing-risk regression models. Groups were categorized based on MiHA disparities in mismatching and matching at the DNA level. Biology of Blood and Marrow Transplantation 2013 19, 274-282DOI: (10.1016/j.bbmt.2012.09.008) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Autosomal MiHA disparity is associated with increased RFS after allo-SCT with a sibling graft. RFS was analyzed in the complete cohort (A) versus recipients of a sibling graft (B) or an MUD graft (C) using the log-rank test. Groups were categorized based on autosomal MiHA disparity in mismatching (black line) and matching (gray line) at the DNA level. Significant P values of multivariate analyses are shown. Biology of Blood and Marrow Transplantation 2013 19, 274-282DOI: (10.1016/j.bbmt.2012.09.008) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Patients with MM undergoing allo-SCT with a related MiHA-mismatched graft show improved RFS. Recipients of sibling grafts were grouped based on autosomal MiHA disparity in mismatching and matching at the DNA level. (A and B) Differences in RFS (A) and relapse rate (B) between these subgroups were analyzed using the log-rank test and Fine-Gray competing-risk regression model, respectively. P values of univariate analyses are given. (C and D) The incidence of cGVHD (C) and disease status (D) were analyzed using the Fisher exact test. (E) Within the total of mismatched MiHA, the relative contribution of each MiHA is depicted. Lim indicates limited; Ext, extensive; Int, intermediate disease; Adv, advanced disease; ns, not significant. Biology of Blood and Marrow Transplantation 2013 19, 274-282DOI: (10.1016/j.bbmt.2012.09.008) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Detection of tetramer-positive MiHA-specific CD8+ T cell responses is associated with improved RFS after allo-SCT. Recipient PBMC samples obtained after allo-SCT were analyzed for the presence of MiHA-specific CD8+ T cells using a dual-color MiHA-multimer flow cytometry assay. Patients were considered to have a positive tetramer response when MiHA-specific CD8+ T cells were found directly after thawing or at 7 days after stimulation with peptide-loaded EBV-LCL. (A) The numbers in the dot plots indicate the percentage of MiHA-specific cells positive for both tetramers (PE and APC) in the CD8+, CD4−, CD14−, CD16−, and CD19− T cell populations. Three representative examples are shown. (B) For each MiHA disparity, the number of tetramer-positive responses (white bars) within the total number of screenings (gray bars) is depicted for the complete cohort of MiHA-mismatched recipients. Percentages indicate the relative number of productive responses. (C and D) RFS was analyzed for the complete cohort of recipients (C) versus recipients of a sibling graft (D) using the log-rank test. Groups were categorized based on detection of MiHA-specific T cell responses (black line) versus no MiHA-specific T cell responses or no mismatching for any of the studied MiHAs (gray line) after allo-SCT. Statistical differences in RFS incidence were analyzed using Kaplan-Meier point estimates and their associated errors; univariate P values are given. Biology of Blood and Marrow Transplantation 2013 19, 274-282DOI: (10.1016/j.bbmt.2012.09.008) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Supplemental Figure 1 Biology of Blood and Marrow Transplantation 2013 19, 274-282DOI: (10.1016/j.bbmt.2012.09.008) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions