Efficacy of 2 Doses of Rituximab on B-Cell and Antidonor Antibody and Outcomes of ABO-Incompatible Living-Donor Pediatric Kidney Transplant

Exp Clin Transplant. 2019 Jan;17(Suppl 1):105-109. doi: 10.6002/ect.MESOT2018.O43.

Abstract

Objectives: Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients.

Materials and methods: Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups.

Results: In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function.

Conclusions: Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.

MeSH terms

  • ABO Blood-Group System / immunology*
  • Age Factors
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Blood Group Incompatibility / immunology*
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Histocompatibility*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Isoantibodies / immunology*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Living Donors*
  • Male
  • Plasmapheresis
  • Risk Factors
  • Rituximab / administration & dosage*
  • Rituximab / adverse effects
  • Splenectomy
  • Time Factors
  • Treatment Outcome

Substances

  • ABO Blood-Group System
  • Immunosuppressive Agents
  • Isoantibodies
  • Rituximab