Prophylaxis and treatment of GVHD: EBMT–ELN working group recommendations for a standardized practice

GVHD remains the major impediment to broader application of allogeneic haematopoietic SCT. It can be prevented completely, but at the expense of other complications, rejection, relapse or delayed immune reconstitution. No optimal prevention or treatment method has been defined. This is reflected by enormous heterogeneity in approaches in Europe. Retrospective comparisons between different policies, although warranted, do not give definite answers. In order to improve the present situation, an European Group for Blood and Marrow Transplantation and the European LeukemiaNet working group has developed in a Delphi-like approach recommendations for prophylaxis and treatment of GVHD in the most common allogeneic transplant setting, transplantation from an HLA-identical sibling or unrelated donor for standard risk malignant disease. The working group proposes these guidelines to be adopted as routine standard in transplantation centres and to be used as comparator in systematic studies evaluating the advantages and disadvantages of practices differing from these recommendations.

[1]  M. Mohty,et al.  Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. , 2011, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[2]  E. Holler,et al.  Consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): first-line and topical treatment of chronic GVHD. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[3]  R. Hoffmann,et al.  Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion. , 1988 .

[4]  L. Norton,et al.  Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs. , 1978, Acta haematologica.

[5]  A. Bacigalupo,et al.  Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. , 2006, Blood.

[6]  L Davies,et al.  Bone marrow transplant. , 1985, Nursing times.

[7]  E. H. Atta,et al.  Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study , 2010, Annals of Hematology.

[8]  H. Einsele,et al.  Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. , 2009, The Lancet. Oncology.

[9]  H. Einsele,et al.  Vaccination of stem cell transplant recipients: recommendations of the Infectious Diseases Working Party of the EBMT , 2005, Bone Marrow Transplantation.

[10]  R. Brand,et al.  Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  M. Turner,et al.  National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[12]  R. Storb,et al.  Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissio , 2003, Blood.

[13]  H. Einsele,et al.  Viral disease prevention after hematopoietic cell transplantation , 2009, Bone Marrow Transplantation.

[14]  F. Frassoni,et al.  Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. , 1991, Blood.

[15]  E. Thiel,et al.  The type of ATG matters -- natural killer cells are influenced differentially by Thymoglobulin, Lymphoglobulin and ATG-Fresenius. , 2007, Transplant immunology.

[16]  M. Flowers,et al.  Secondary treatment of acute graft-versus-host disease: a critical review. , 2012, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[17]  H. Einsele,et al.  Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009 , 2010, Bone Marrow Transplantation.

[18]  N. Sacchi,et al.  Haematopoietic stem cell donor registries: World Marrow Donor Association recommendations for evaluation of donor health , 2008, Bone Marrow Transplantation.

[19]  H. Greinix,et al.  National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease , 2015 .

[20]  A. Gratwohl,et al.  A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow Transplantation (EBMT) , 1997, Bone Marrow Transplantation.

[21]  R. Suzuki,et al.  Low incidences of acute and chronic graft-versus-host disease after unrelated bone marrow transplantation with low-dose anti-T lymphocyte globulin , 2012, International Journal of Hematology.

[22]  J. Gribben,et al.  Graft rejection following HLA matched T‐lymphocyte depleted bone marrow transplantation , 1986, British journal of haematology.

[23]  J. Thomas,et al.  Differential effects of horse ATG and rabbit ATG on T cell and T cell subset levels measured by monoclonal antibodies. , 1984, Transplantation proceedings.

[24]  G. Dini,et al.  Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. , 1998, Blood.

[25]  B. Sandmaier,et al.  Defining the intensity of conditioning regimens: working definitions. , 2009, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[26]  J. Wingard,et al.  First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. , 2012, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[27]  H. Deeg,et al.  Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. , 1986, The New England journal of medicine.

[28]  Daniel Wolff,et al.  National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[29]  A. Gratwohl,et al.  Prophylaxis and treatment of GVHD after allogeneic haematopoietic SCT: a survey of centre strategies by the European Group for Blood and Marrow Transplantation , 2012, Bone Marrow Transplantation.

[30]  A. Gratwohl,et al.  Allogeneic hematopoietic stem cell donation—standardized assessment of donor outcome data: A consensus statement from the Worldwide Network for Blood and Marrow Transplantation (WBMT) , 2013, Bone Marrow Transplantation.

[31]  T. Ruutu.  Bone marrow transplantation. , 1997, Annales chirurgiae et gynaecologiae.

[32]  M. Mohty,et al.  Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond , 2007, Leukemia.

[33]  S. Fischer,et al.  Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. , 2006, Blood.

[34]  R. Storb.  Nonmyeloablative preparative regimens: how relevant for acute myelogenous leukemia? , 2001, Leukemia.

[35]  P. Bruzzi,et al.  Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[36]  A. Thiébaut,et al.  European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 Update , 2011, Bone Marrow Transplantation.