Rituximab Reduces the Incidence of Acute Graft Versus Host Disease in an Unselected Series of Twenty-One Patients Undergoing Allogeneic Stem Cell Transplantation at a Single Center.

Recent evidence highlights an implication of B lymphocytes in the development and sustainment of chronic graft versus host disease (cGvH). The monoclonal anti-CD20-antibody rituximab has proven effective against steroid refractory cGvH. Data on the role of B lymphocytes in acute GvH (aGvH) is sparse. We report on a reduction of the incidence of aGvH in patients receiving rituximab as an element of conditioning as compared to patients conditioned without rituximab. All 6 patients receiving rituximab suffered from CD20 positive Non-Hodgkin-Lymphoma (NHL) and received cyclosporine and mycophenolate immunosuppression. Immunosuppression in the other 15 patients was achieved either with cyclosporine and mycophenolate (N=11) or cyclosporine and methotrexate (N=4). All patients except for one received dose reduced conditioning. Only patients beyond day 25 are included in the analysis; as of july 20th, 2006 median follow up is 151 days (range 27 to 322 days). Out of six patients receiving rituximab as an element of conditioning, one (16.7 %) developed moderate aGvH. Out of 15 patients who did not receive rituximab during conditioning, 10 (66.7 %) developed moderate to severe aGvH. Two patients developed severe acute GvH after early cessation of immunosuppression and/or donor lymphocyte infusion for progressive disease. If removed from this analysis, 8 out of 13 patients (61.5 %) developed aGvH after conditioning without rituximab. Taken together, these data present a trend that in patients conditioned with rituximab acute GvH occurs less frequently. These are amongst the first data indicating that rituximab might suppress the development of acute GvH. They are in accordance with work published before yet this is the first study systematically comparing two groups of patients. At present, no data exploring the influence of CD20 positive B lymphocytes or the effect of rituximab on graft-versus-tumor effects exist. It therefore remains to be investigated whether the suggested suppression of GvH by rituximab benefits overall survival by reducing transplantation related mortality or whether it is associated with a higher relapse rate due to an abrogated graft versus tumor effect. Furthermore, it remains to be elucidated whether the administration of rituximab before transplantation or during the restoration of the allogeneic immune system exerts prophylactic effects against cGvH and whether this influences both graft versus tumor effects and survival. Finally, we conclude that the addition of rituximab to the treatment of severe steroid refractory acute graft versus host reactions has to be tested in randomized trials.