A randomized, prospective trial of rituximab for acute rejection in pediatric renal transplantation.
We report 1-year outcomes of a randomized study of Rituximab versus standard-of-care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of biopsy confirmed, acute transplant rejection with B-cell infiltrates, in 20 consecutive recipients (2-23 years). Graft biopsies, with Banff and CADI scores, CD20 and C4d stains, were performed at rejection and 1 and 6 months later. Peripheral blood CMV, EBV and BK viral loads, graft function, DSA, immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions were given with a high index of safety without HACA development and increased infections complications. Rituximab therapy resulted in complete tissue B-cell depletion and rapid peripheral B-cell depletion. Peripheral CD19 cells recovered at a mean time of approximately 12 months. There were some benefits for the recovery of graft function (p = 0.026) and improvement of biopsy rejection scores at both the 1- (p = 0.0003) and 6-month (p < 0.0001) follow-up biopsies. Reappearance of C4d deposition was not seen on follow-up biopsies after Rituximab therapy, but was seen in 30% of control patients. There was no change in DSA in either group, independent of rejection resolution. This study reports safety and suggests further investigation of Rituximab as an adjunctive treatment for B-cell-mediated graft rejection.
Zarkhin
V
V
Department of Pediatrics, Stanford University Medical Center, Stanford, CA, USA.
Li
L
L
Kambham
N
N
Sigdel
T
T
Salvatierra
O
O
Sarwal
M M
MM
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D000069283:Rituximab; D014184:Transplantation, Homologous; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab