Steroid-Refractory Acute GVHD: Predictors and Outcomes
Jason R. Westin,Rima M. Saliba,Marcos de Lima,Amin M. Alousi,Chitra Hosing,Muzaffar H. Qazilbash,Issa F. Khouri,Elizabeth J. Shpall,Paolo Anderlini,Gabriela Rondon,Borje S. Andersson,Richard E. Champlin,Daniel R. Couriel +12 more
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TLDR
S Severity of aGVHD, hyperacute GVHD, and sex mismatch could be integrated into prognostic scoring systems which may allow for pretreatment identification of patients unlikely to benefit from standard therapy with corticosteroids.Abstract:
Patients with steroid-resistant acute graft versus host disease (aGVHD) have a dismal prognosis, with mortality rates in excess of 90%. We sought to identify a subgroup of patients less likely to benefit from initial therapy with corticosteroids as well as the impact of response on day 14 on outcome. Retrospective evaluation was performed of patients with biopsy-proven aGVHD treated with corticosteroids after allogeneic HSCT at M.D. Anderson Cancer Center from 1998 through 2002 (N = 287). Overall response to first-line therapy on day 14 was 56%. Grade III-IV aGVHD and hyperacute GVHD were the most significant factors predicting failure. Patients who fail to respond to steroids by day 14 should be considered for clinical trials. Severity of aGVHD, hyperacute GVHD, and sex mismatch could be integrated into prognostic scoring systems which may allow for pretreatment identification of patients unlikely to benefit from standard therapy with corticosteroids.read more
Citations
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Journal ArticleDOI
Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey
Robert Zeiser,Andreas Burchert,Claudia Lengerke,Mareike Verbeek,Kristina Maas-Bauer,S K Metzelder,Silvia Spoerl,Markus Ditschkowski,Matyas Ecsedi,Katja Sockel,Francis Ayuk,Salem Ajib,F.S. de Fontbrune,Il-Kang Na,Livius Penter,Udo Holtick,Dominik Wolf,Esther Schuler,Everett Meyer,Petya Apostolova,Hartmut Bertz,Reinhard Marks,Michael Lübbert,Ralph Wäsch,Christoph Scheid,Friedrich Stölzel,Rainer Ordemann,Gesine Bug,Guido Kobbe,Robert S. Negrin,Mats Brune,Alexandros Spyridonidis,Annette Schmitt-Gräff,W.J.F.M. van der Velden,Gerwin Huls,Stephan Mielke,G. U. Grigoleit,Jürgen Kuball,Ryan Flynn,Gabriele Ihorst,Jing Du,Bruce R. Blazar,Renate Arnold,Kröger N,Jakob Passweg,Jörg Halter,Gérard Socié,Dietrich W. Beelen,Christian Peschel,Andreas Neubauer,Jürgen Finke,Justus Duyster,N von Bubnoff +52 more
TL;DR: Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
Journal ArticleDOI
Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease
Robert Zeiser,Nikolas von Bubnoff,Jason Butler,Mohamad Mohty,Dietger Niederwieser,Reuven Or,Jeff Szer,Eva Maria Wagner,Tsila Zuckerman,Bruyère Mahuzier,Judith Xu,Celine Wilke,Kunal K. Gandhi,Gérard Socié +13 more
TL;DR: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy.
Journal ArticleDOI
ST2 as a Marker for Risk of Therapy-Resistant Graft-versus-Host Disease and Death
Mark Vander Lugt,Thomas Braun,Samir M. Hanash,Jerome Ritz,Vincent T. Ho,Joseph H. Antin,Qing Zhang,Chee Hong Wong,Hong Wang,Alice Chin,Aurelie Gomez,Andrew C. Harris,John E. Levine,Sung Won Choi,Daniel R. Couriel,Pavan Reddy,James L.M. Ferrara,Sophie Paczesny,Sophie Paczesny +18 more
TL;DR: ST2 levels measured at the initiation of therapy for GV HD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplanting.
Journal ArticleDOI
Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease.
Silvia Spoerl,Nimitha R. Mathew,Michael Bscheider,Annette Schmitt-Graeff,Sophia Chen,Tony A. Mueller,Mareike Verbeek,Julius C. Fischer,Vera Otten,Martina Schmickl,Kristina Maas-Bauer,Jürgen Finke,Christian Peschel,Justus Duyster,Hendrik Poeck,Robert Zeiser,Nikolas von Bubnoff +16 more
TL;DR: Ruxolitinib represents a novel targeted approach in GVHD by suppression of proinflammatory signaling that mediates tissue damage and by promotion of tolerogenic Treg cells.
Journal ArticleDOI
A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study
John E. Levine,Thomas Braun,Andrew C. Harris,Ernst Holler,Austin Taylor,Austin Taylor,Holly K. Miller,John M. Magenau,Daniel J. Weisdorf,Vincent T. Ho,Javier Bolaños-Meade,Amin M. Alousi,James L.M. Ferrara,James L.M. Ferrara +13 more
TL;DR: This work used the concentrations of three recently validated biomarkers (TNFR1, ST2, and Reg3α) to create an algorithm that computed the probability of non-relapse mortality 6 months after GVHD onset for individual patients in the training set alone and evaluated the algorithm in the test set, and again in an independent validation set.
References
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Book ChapterDOI
Regression Models and Life-Tables
TL;DR: The analysis of censored failure times is considered in this paper, where the hazard function is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time.
Journal Article
1994 Consensus Conference on Acute GVHD Grading.
Donna Przepiorka,Daniel J. Weisdorf,Paul J. Martin,Hans G. Klingemann,Beatty P,Hows J,Thomas Ed +6 more
TL;DR: Reports of GVHD prevention trials should include an accurate description of the grading system used and should report actuarial rates of grades II-IV and III-IV GV HD corrected for graft failure and potential interventions for early relapse.
Journal ArticleDOI
The analysis of failure times in the presence of competing risks.
Ross L. Prentice,John D. Kalbfleisch,A. V. Peterson,Nancy Flournoy,Vernon T. Farewell,Norman E. Breslow +5 more
TL;DR: It is argued that the problem of estimation of failure rates under the removal of certain causes is not well posed until a mechanism for cause removal is specified, and a method involving the estimation of parameters that relate time-dependent risk indicators for some causes to cause-specific hazard functions for other causes is proposed for the study of interrelations among failure types.
Journal ArticleDOI
Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research.
Sergio Giralt,Karen K. Ballen,Douglas Rizzo,Andreas Bacigalupo,Mary M. Horowitz,Marcelo C. Pasquini,Brenda M. Sandmaier +6 more
TL;DR: Although HCT professionals have not reached a consensus on what constitutes a RIC regimen, most accept currently used criteria and operational definitions, and these results support the continued use of current criteria for RIC regimens until a consensus statement can be developed.
Journal ArticleDOI
A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment
Paul J. Martin,Gary Schoch,LD Fisher,Vera Byers,Frederick R. Appelbaum,George B. McDonald,Rainer Storb,John A. Hansen +7 more
TL;DR: The times to treatment failure and the proportions of patients in various response categories were similar for primary and secondary treatment, suggesting that the potential efficacy of new immunosuppressive agents for treatment of acute GVHD can be assessed meaningfully in patients who have not responded adequately to initial therapy.
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