Title: | Association of disparities in known minor histocompatibility antigens with relapse-free survival and graft-versus-host disease after allogeneic stem cell transplantation |
Author(s): | Hobo, W.A. ; Broen, K.C. ; Velden, W.J. van der ; Greupink-Draaisma, A.L.; Adisty, N.; Wouters, Y.; Kester, M.; Fredrix, H. ; Jansen, J.H. ; Reijden, B.A. van der ; Falkenburg, J.H.F.; Witte, T.J. de ; Preijers, F.W. ; Schattenberg, T. ; Feuth, T. ; Blijlevens, N.M.A. ; Schaap, N.P. ; Dolstra, H. |
Publication year: | 2013 |
Source: | Biology of Blood and Marrow Transplantation, vol. 19, iss. 2, (2013), pp. 274-282 |
ISSN: | 1083-8791 |
DOI: | https://doi.org/10.1016/j.bbmt.2012.09.008 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/118016 ![]() |
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Subject: | N4i 2: Invasive mycoses and compromised host ONCOL 3: Translational research NCEBP 2: Evaluation of complex medical interventions NCMLS 2: Immune Regulation ONCOL 3: Translational research ONCOL 3: Translational research NCMLS 2: Immune Regulation Tijdelijke code tbv inlezen publicaties Radboudumc - Alleen voor gebruik door Radboudumc |
Organization: | Laboratory of Hematology Haematology Tumorimmunology Health Evidence |
Former Organization: | Epidemiology, Biostatistics & HTA |
Journal title: |
Biology of Blood and Marrow Transplantation
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Volume: | vol. 19 |
Issue: | iss. 2 |
Page start: | p. 274 |
Page end: | p. 282 |
Abstract: |
Allogeneic stem cell transplantation (allo-SCT) can induce remission in patients with hematologic malignancies due to graft-versus-tumor (GVT) responses. This immune-mediated antitumor effect is often accompanied by detrimental graft-versus-host disease (GVHD), however. Both GVT and GVHD are mediated by minor histocompatibility antigen (MiHA)-specific T cells recognizing peptide products from polymorphic genes that differ between recipient and donor. In this study, we evaluated whether mismatches in a panel of 17 MiHAs are associated with clinical outcome after partially T cell-depleted allo-SCT. Comprehensive statistical analysis revealed that DNA mismatches for one or more autosomal-encoded MiHAs was associated with increased relapse-free survival in recipients of sibling transplants (P = .04), particularly in those with multiple myeloma (P = .02). Moreover, mismatches for the ubiquitous Y chromosome-derived MiHAs resulted in a higher incidence of acute GVHD grade III-IV (P = .004), whereas autosomal MiHA mismatches, ubiquitous or restricted to hematopoietic cells, were not associated with severe GVHD. Finally, we found considerable differences among MiHAs in their capability of inducing in vivo T cell responses using dual-color tetramer analysis of peripheral blood samples collected after allo-SCT. Importantly, detection of MiHA-specific T cell responses was associated with improved relapse-free survival in recipients of sibling transplants (P = .01). Our findings provide a rationale for further boosting GVT immunity toward autosomal MiHAs with a hematopoietic restriction to improve outcomes after HLA-matched allo-SCT.
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