Allogeneic hematopoietic cell transplantation following minimal intensity conditioning: predicting acute graft-versus-host disease and graft-versus-tumor effects

Abstract

Most patients with hematologic malignancies have received extensive chemotherapy before hematopoietic cell transplantation (HCT), resulting in neutropenia, lymphocytopenia, and use of antibiotics. Accordingly, patients have a wide range of neutrophil counts, lymphocyte counts, and previous antibiotic use. The minimal toxicity of the current conditioning regimen allowed us to ask whether peritransplantation neutrophil or lymphocyte levels influences the risks of acute graft-versus-host disease (GVHD) or relapse. We analyzed outcomes in 459 patients age 7-75 years (median, 57 years) who received conditioning with fludarabine and low-dose total body irradiation for HLA-matched HCT. We report 2 key findings. First, low neutrophil nadirs within the first 3 weeks post-HCT had significant associations with increased risks of acute GVHD and 5-year nonrelapse mortality, but showed no association with the risk of relapse. Second, high lymphocyte counts immediately before HCT had significant associations with reduced risks of relapse and overall mortality, but no association with the risks of GVHD or nonrelapse mortality. These findings suggest that the immunologic mechanisms involved in acute GVHD might differ from those that initiate graft-versus-tumor effects.