The Impact of Alemtuzumab as a Component of Conditioning Regimens on Transplantation Outcomes in a Setting of CMV-Seropositive Recipient and Donor.

Background: Graft-versus-host disease (GVHD) is one of the main issues for allogenic stem cell transplantation (SCT). Previous studies demostrated that in vivo administration of alemtuzumab (an anti-CD52 antibody) was effective to decrease the incidence of GVHD after allogenic SCT. However, due to delayed immune reconstruction, graft failure or infection is concerned. We investigated the impact of in vivo administration of alemtuzumab on the post-transplantation outcomes.

Patients and methods: Thirty-five patients entered a pilot study employing allogenic SCT with alemtuzumab-containing conditioning regimen in two centers (KNUH, CNUH). We evaluated the clinical outcomes, complications and their relationship with dose of alemtuzumab.

Results: The median dose of alemtuzumab was 50mg (range, 20–75) which was not adjusted on body weight and surface. All recipients (9 BM, 26 PB) and donors were CMV-seropositive before transplantion. The median survival was 14.03 months and 2 year survival rate was 47.0%. The probability of nonrelapse mortality at 90 days and 1 year was 11.4% and 22.8%, respectively. The cumulative incidence of grade II-IV acute GVHD at day 90 was 37.1%. The overall incidence of chronic GVHD was 20.8% and the incidence of extensive chronic GVHD was only 8.3%. The cumulative incidence of CMV antigenemia was 70.2%, which has been well controlled with preemptive ganciclovir treatment, and two patients with CMV antigenemia developed into CMV disease. The febrile episode was 37.1% but the duration was relatively short (median, 3 days). There were no differenecies in engraft (P = 0.573), acute and chronic GVHD (P = 0.359, P = 0.335, respectively), relapse (P = 0.849), mortality (P = 0.229), CMV antigenemia (P = 0.227) or overall survival (P = 0.51) between two groups (treated with ≥50mg of alemtuzumab vs. <50mg).

Conclusion: Our study has shown that alemtuzumab is effective for GVHD prevention but correlated with high incidence of CMV antigenemia regardless of its dose. As CMV antigenemia was easily controllable with preemptive ganciclovir, the conditioning regimen containing alemtuzumab seems hopeful especially in a setting of CMV-seropositive recipient and donor with a high risk of GVHD.