Histological evaluation of acute mucocutaneous graft-versus-host disease in nonmyeloablative hematologic stem cell transplants with an observation predicting an increased risk of progression to chronic graft-versus-host disease

Abstract

The incorporation of nonmyeloablative conditioning prior to the transplantation of allogeneic hematopoietic cells has emerged as an alternative to myeloablative chemo- and/or radiotherapy for the treatment of hematologic malignancies. Graft-versus-host disease (GVHD) remains a significant complication of both types of hematopoietic cell transplantation (HCT). The clinical phenomenon of late-onset (>100 days after HCT) acute GVHD recently has been described following nonmyeloablative allogeneic transplantation (NMAT); however, there has been no detailed histologic description of acute GVHD in this setting. We sought to characterize the histopathologic features of acute GVHD following NMAT. The clinical and pathologic features of 20 patients with acute GVHD following NMAT over a three-year period were reviewed. Late-onset acute GVHD was diagnosed in 10 of 20 patients with a mean onset of 109.8 days (range 8-410 days); eight (40%) of these subjects with acute GVHD also had concomitant histologic features of chronic lichenoid chronic GVHD. Cases with "composite" histologic features were more likely to progress to fully developed chronic GVHD compared to those without this finding (87.5% vs 25%, P < 0.01). These findings support the existence of late-occurring mucocutaneous GVHD after NMAT and define a strong clinical/laboratory predictor for the subsequent development of chronic GVHD. Patients with composite skin GVHD may benefit from an earlier, more aggressive immunosuppressive interventional strategy.