Successful Treatment of Severe Acute Intestinal Graft-versus-Host Resistant to Systemic and Topical Steroids with Alemtuzumab

Abstract

Development of severe steroid-resistant acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with poor outcome. The humanized monoclonal antibody alemtuzumab was shown to be effective in GVHD prophylaxis in conditioning regimens before allogeneic HCT. We evaluated the efficacy and safety of alemtuzumab in 20 patients with histologically confirmed steroid refractory grade III and IV intestinal GVHD after related and unrelated HCT. Overall response rate was 70%, with complete response in 35%. Despite the severe grade of GVHD in our patients, the median survival of 280 days and 1-year overall survival (OS) of 50% were superior or comparable to those associated with other treatment options. Cytomegalovirus (CMV) reactivation, bacterial infection, and invasive aspergillosis were frequent complications; however, infection was not a significant predictor for survival. These data suggest that treatment with alemtuzumab has favorable activity in severe intestinal GVHD after allogeneic HCT, but emphasize the importance of careful monitoring and anti-infectious supportive care.