Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial

Jürgen Finke, Claudia Schmoor, Wolfgang A. Bethge, Hellmut D. Ottinger, Matthias Stelljes, Axel R. Zander, Liisa Volin, Dominik A. Heim, Rainer Schwerdtfeger, Karin Kolbe, Jiri Mayer, Johan A. Maertens, Werner Linkesch, Ernst Holler, Vladimir Koza, Martin Bornhäuser, Hermann Einsele, Hartmut Bertz, Olga Grishina, Gérard SociéH. Schneeberger, G. Börner, H. J. Gamperl, J. Jauch, J. Petan, A. Kainz, C. Schmoor, O. Grishina, Ch Müller, J. Scheele, B. Schilling, M. Kaufmann, R. Tostmann, A. Kollmer, S. Nuss, C. Wenig, H. Bertz, M. Egger, W. A. Bethge, H. Einsele, R. K.F. Müller, M. Ḧntschel, H. D. Ottinger, R. Trenschel, M. Stelljes, A. R. Zander, N. M. Kröger, F. A. Ayuketang, C. Wolschke, R. Schwerdtfeger, J. Kaltenḧuser, T. Stübig, R. H. Taube, K. Kolbe, S. Thomas, A. Ullmann, A. Schulze-Bergkamen, E. Holler, J. Hahn, M. Bornḧuser, H. J. Kolb, R. Reibke, H. Wandt, K. Schaefer-Eckart, E. Gluckman, H. Esperou, M. Robin, M. Michallet, F. Nicolini, A. Buzyn, M. T. Rubio, I. Yakoub-Agha, J. P. Jouet, M. O. Petillon, P. Bordigoni, L. Clement, A. Salmon, P. Feugier, T. Ruutu, L. Volin, E. Juvonen, A. Nihtinen, K. Remes, M. Putkonen, M. Iẗl̈, M. Kauppila, J. Mayer, M. Krejci, Y. Brychtova, V. Koza, M. Karas, J. Voglova, J. Lebavy, P. Zak, D. Heim, A. Gratwohl, J. Passweg, C. Arber, A. Tsakiris, W. Linkesch, S. Reitter, P. B. Staber, D. Lutz, O. Krieger, K. Theunissen, M. Boogaerts, G. Verhoef, J. Rowe, T. Rosenvald-Zuckermann, M. Shapira, R. Or, I. Resnik, A. Nagler, A. Shimoni, R. Yerushalmi, J. Sierra, D. Valcarcel, J. A. Perez Simon, M. Astorga, A. Bosi, S. Guidi

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53 Scopus citations

Abstract

Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD.

Original languageEnglish
Pages (from-to)1716-1726
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number11
DOIs
StatePublished - 1 Nov 2012
Externally publishedYes

Keywords

  • Allogeneic hematopoietic stem-cell transplantation
  • Graft-versus-host-disease prophylaxis
  • HLA-matching

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