Late-Onset Neutropenia and Acute Rejection in ABO-Incompatible Kidney Transplant Recipients Receiving Rituximab.

Abstract

Recently, a new avenue in the management of ABO-incompatible kidney transplantation has been presented with the introduction of an anti-CD20 monoclonal antibody, rituximab. In May 2006, we started our program using this antibody for ABO-incompatible kidney transplantations. Using rituximab, we have experienced successful ABO-incompatible renal transplantations without splenectomy as well as in recipients with high pre-transplant anti-A/B antibody titers. At our institution, rituximab (150 mg/m2) was administered twice at 2 weeks priorto and on the day of transplantation except for elderly recipients. The recipients aged 65 years and older received only a single dose of 150 mg/m2 rituximab at 2 weeks prior to transplantation. An increasingly recognized toxicity of rituximab is late-onset neutropenia (LON), defined as unexplained grade III-IV neutropenia occurring at least 4 weeks after the last dose of rituximab in the absence of an alternative explanation. Patients and Methods Between May 2006 and December 2011, 25 patients who received rituximab underwent successful ABO-incompatible kidney transplantations. These 25 cases were enrolled as the subjects in this study. LON was defined as grade III to IV neutropenia after the last administration of rituximab, in the absence of any alternative reason to explain its occurrence. Results Twelve recipients (48%) experienced LON 1-11 months after transplantation. Five of the 12 patients (41.6%) who developed LON had an episode of biopsy-confirmed acute cellular rejection, as compared with one of the remaining 13 patients (7.7%) who did not develop LON. Moreover, 3 patients who experienced LON developed steroid and deoxyspergualin-resistant acute cellular rejection, and they required OKT-3 administration. Conclusion The frequency of acute cellular rejection tended to be higher in ABO-incompatible kidney transplant recipients with LON than in those without LON. Our findings suggest that recipients who develop LON after rituximab administration may be at an increased risk for acute cellular rejection.