[Role of monoclonal antibodies in the treatment of acute graft versus host disease].
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice of hematologic malignancies. Acute graft versus host disease (GvHD) is common but important after HSCT, being directly related to graft versus leukemia effect. Recent experimental data indicate that acute GvHD develops in three phases: epithelial-cell injury caused by the conditioning regimen (Pre transplant phase); activation of donor T lymphocytes (T-cell activation phase); and the effector phase. Unfortunately, little progress has been done in the treatment of acute GvHD. The first line treatment is usually high-dose steroids for patients presenting more than grade II. However, 40% of those patients are resistant to this treatment. Other immunosuppressive treatments are then required, generally associated with limited efficacy and high morbidity. Several approaches using monoclonal antibodies against cytokines or other molecules involve in the physiopathology of acute GvHD have been used, especially for the treatment of steroid resistant acute GvHD. The aim of this review is first to remind the main characteristics of acute GvHD pathophysiology. In a second part, we present an updated overview of the mainly used monoclonal antibodies in the treatment of acute GvHD (anti-TNFalpha, anti-interleukin-2 receptor and anti-CD147).
Bay
Jacques-Olivier
JO
Unité de transplantation médullaire, Centre Jean-Perrin, 58, rue Montalembert, 63011 Clermont-Ferrand. Olivier.bay@cjp.fr
Cabrespine
Aurélie
A
Peffault de Latour
Régis
R
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D051926:Basigin / Q000276:immunology; D000068800:Etanercept; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D051926:Basigin; D000069285:Infliximab; C079843:inolimomab; D000068800:Etanercept