Favorable Impact of Short Term Methotrexate on Early Immune Reaction and Non-Relapse Mortality in Umbilical Cord Blood Transplantation for Adult Patients.

Abstract

Cord blood transplantation (CBT) represents an attractive alternative for patients with advanced hematological malignancy who lack matched related or unrelated donors. Adult patients receiving myeloablative or reduced-intensity CBT display a 90% chance of engraftment, but also experience a 50% rate of transplant-related mortality. Post-transplant immune disorders including early immune reactions and acute GVHD are problematic in CBT for adult patients. These reactions and/or additional immunosuppressive therapy might increase the risk of infection and organ dysfunction, leading to high rates of transplantation-related mortality. However, optimal prophylaxis and management for immune reactions have not been established in CBT. We investigated retrospectively whether intensive graft-versus-host disease (GVHD) prophylaxis has a prognostic impact on CBT. Post-CBT immune reactions were classified according to time course as pre-engraftment immune reaction (PIR), engraftment syndrome (ES) or acute GVHD. Between March 2001 and September 2003, a total of 77 patients underwent CBT at 8 centers of the Nagoya Blood and Marrow Transplantation Group (NBMTG). Median age of patients was 48 years (range, 18–69 years). Preparative regimens were myeloablative (n=31) or reduced-intensity (n=46). Acute GVHD prophylaxis included cyclosporine alone (n=23), tacrolimus alone (n=12), cyclosporine plus short-term methotrexate (n=17), tacrolimus plus short-term MTX (n=23) or cyclosporine plus methylprednisolone (n=2). Cumulative incidences of PIR, ES and grade I-IV GVHD were 38%, 12% and 29%, respectively. Short-term MTX exerted significant favorable effects on PIR in univariate analysis (hazard ratio, 0.41; 95% confidence interval, 0.19–0.89) and on non-relapse mortality (NRM) in multivariate analysis (hazard ratio, 0.36; 95% confidence interval, 0.16–0.81). On the other hand, PIR occurred in 35% of patients with cyclosporine and 37% with tacrolimus. Short-term MTX appears to offer optimal GVHD prophylaxis to reduce PIR and improve NRM. [Display omitted]