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35-OR: Rituximab prophylaxis reduces acute rejection risk in pre-sensitized renal allograft recipients
S118
35-OR
Abstracts
RITUXIMAB PROPHYLAXIS REDUCES ACUTE REJECTION RISK IN PRE-SENSITIZED RENAL ALLOGRAFT RECIPIENTS. D. Dadhania,1,2 V. Sharma,1,2 R. Friedlander,1 K. Wang,1 M. Aull,1 A. Menon,1 S. Seshan,1 M. Fotino,2 M. Suthanthiran.1,2 1Immunogenetics & Transplantation Center, Rogosin Institute, NY, NY, USA; 2Transplantation Medicine, NYPH-Cornell, NY, NY, USA. Several interventions including plasmapheresis, intravenous immune gamma globulin (IVIG) and Rituximab, a humanized mAbs directed at B cell CD20 antigen are being investigated to manage organ graft recipients with pre-transplant donor specific antibodies (DSA). In a single center study, we investigated the efficacy of Rituximab in reducing the risk of acute rejection (AR) in renal allograft recipients with pre-transplant DSA and positive donor T &/or B cell flow cytometry crossmatch. DSA were detected by a solid phase assay using Luminex platform. The study cohort was comprised of 47 renal allograft recipients with a positive donor T &/or B cell flow cytometry cross match and a positive DSA using the Luminex platform. All but one recipient was negative in the donor T cell complement dependent cytotoxicity assay. Thirty of the 47 subjects were treated with Rituximab in the pre or peri-transplant period; 17 subjects were transplanted prior to the development of our Rituximab protocol and thus did not receive Rituximab. The risk of AR was significantly decreased with preemptive Rituximab therapy; the odds ratio for AR was 0.18 (95% Confidence Intervals of .05, 0.67) when Rituximab therapy was given preemptively to the recipients with pre-transplant DSA. Our single center study demonstrates that Rituximab prophylaxis reduces the risk of acute rejection in renal allograft graft recipients with DSA. A randomized controlled trial of Rituximab for AR prophylaxis appears worthy. TABLE 1 AR group No AR group
Rituximab Rx 5 (17%) 25 (83%)
No Rituximab Rx 9 (53%) 8 (47%) P⫽0.009
P value by 2x2 contingency table
36-OR
PROSPECTIVE IMMUNE MONITORING OF PERFORIN AND GRANZYME B GENE EXPRESSION IN THE PERIPHERAL BLOOD DETECTS RENAL ALLOGRAFT REJECTION. Q. Zhang,1 J.L. Veale,2 D.W. Gjertson,1 B. Suphamai,3 P.T. T. Pham,3 G.M. Danovitch,2 A.H. Wilkinson,3 A.H. Gritsch,2 E.F. Reed.1 1UCLA Immunogenetics Center, Depart. of Pathology, UCLA, Los Angeles, USA; 2 Urology, UCLA, Los Angeles, USA; 3Nephrology, UCLA, Los Angeles, USA. Acute rejection remains one of the causes of early graft loss after renal transplantation and increases the risk for development of chronic allograft nephropathy. Development of a non-invasive test that would monitor for rejection would represent a major advancement in transplantation. In a previous retrospective study, we showed that monitoring perforin and granzyme-B gene expression levels in the peripheral blood was accurate in detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR). The goal of this study was to validate the accuracy of the perforin and granzyme-B gene expression test for the diagnosis of renal allograft rejection in a prospective study. Renal transplant recipients (n⫽34) undergoing biopsy were tested for peripheral blood mRNA expression on of perforin and granzyme B by real-time PCR. ACR and AMR were diagnosed by Banff criteria. Recipients diagnosed with ACR (n⫽7) or AMR(n⫽3) had higher perforin and granzyme B levels compared to non-rejectors (n⫽24) (p⬍0.008 for perforin, and p⬍0.015 for granzyme B). Patients with high levels of perforin and granzyme-B had a probability of rejecting that was 7 times greater than patients with low levels of granzyme B (cutoff value⫽120 for perforin, 125 for granzyme-B). Perforin and granzyme B had sensitivities of 80% and specificities of 70% in predicting rejection. Prospective monitoring of perforin and granzyme B gene expression in the peripheral blood is a reliable method for detecting both ACR and AMR.
35-OR
Abstracts
RITUXIMAB PROPHYLAXIS REDUCES ACUTE REJECTION RISK IN PRE-SENSITIZED RENAL ALLOGRAFT RECIPIENTS. D. Dadhania,1,2 V. Sharma,1,2 R. Friedlander,1 K. Wang,1 M. Aull,1 A. Menon,1 S. Seshan,1 M. Fotino,2 M. Suthanthiran.1,2 1Immunogenetics & Transplantation Center, Rogosin Institute, NY, NY, USA; 2Transplantation Medicine, NYPH-Cornell, NY, NY, USA. Several interventions including plasmapheresis, intravenous immune gamma globulin (IVIG) and Rituximab, a humanized mAbs directed at B cell CD20 antigen are being investigated to manage organ graft recipients with pre-transplant donor specific antibodies (DSA). In a single center study, we investigated the efficacy of Rituximab in reducing the risk of acute rejection (AR) in renal allograft recipients with pre-transplant DSA and positive donor T &/or B cell flow cytometry crossmatch. DSA were detected by a solid phase assay using Luminex platform. The study cohort was comprised of 47 renal allograft recipients with a positive donor T &/or B cell flow cytometry cross match and a positive DSA using the Luminex platform. All but one recipient was negative in the donor T cell complement dependent cytotoxicity assay. Thirty of the 47 subjects were treated with Rituximab in the pre or peri-transplant period; 17 subjects were transplanted prior to the development of our Rituximab protocol and thus did not receive Rituximab. The risk of AR was significantly decreased with preemptive Rituximab therapy; the odds ratio for AR was 0.18 (95% Confidence Intervals of .05, 0.67) when Rituximab therapy was given preemptively to the recipients with pre-transplant DSA. Our single center study demonstrates that Rituximab prophylaxis reduces the risk of acute rejection in renal allograft graft recipients with DSA. A randomized controlled trial of Rituximab for AR prophylaxis appears worthy. TABLE 1 AR group No AR group
Rituximab Rx 5 (17%) 25 (83%)
No Rituximab Rx 9 (53%) 8 (47%) P⫽0.009
P value by 2x2 contingency table
36-OR
PROSPECTIVE IMMUNE MONITORING OF PERFORIN AND GRANZYME B GENE EXPRESSION IN THE PERIPHERAL BLOOD DETECTS RENAL ALLOGRAFT REJECTION. Q. Zhang,1 J.L. Veale,2 D.W. Gjertson,1 B. Suphamai,3 P.T. T. Pham,3 G.M. Danovitch,2 A.H. Wilkinson,3 A.H. Gritsch,2 E.F. Reed.1 1UCLA Immunogenetics Center, Depart. of Pathology, UCLA, Los Angeles, USA; 2 Urology, UCLA, Los Angeles, USA; 3Nephrology, UCLA, Los Angeles, USA. Acute rejection remains one of the causes of early graft loss after renal transplantation and increases the risk for development of chronic allograft nephropathy. Development of a non-invasive test that would monitor for rejection would represent a major advancement in transplantation. In a previous retrospective study, we showed that monitoring perforin and granzyme-B gene expression levels in the peripheral blood was accurate in detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR). The goal of this study was to validate the accuracy of the perforin and granzyme-B gene expression test for the diagnosis of renal allograft rejection in a prospective study. Renal transplant recipients (n⫽34) undergoing biopsy were tested for peripheral blood mRNA expression on of perforin and granzyme B by real-time PCR. ACR and AMR were diagnosed by Banff criteria. Recipients diagnosed with ACR (n⫽7) or AMR(n⫽3) had higher perforin and granzyme B levels compared to non-rejectors (n⫽24) (p⬍0.008 for perforin, and p⬍0.015 for granzyme B). Patients with high levels of perforin and granzyme-B had a probability of rejecting that was 7 times greater than patients with low levels of granzyme B (cutoff value⫽120 for perforin, 125 for granzyme-B). Perforin and granzyme B had sensitivities of 80% and specificities of 70% in predicting rejection. Prospective monitoring of perforin and granzyme B gene expression in the peripheral blood is a reliable method for detecting both ACR and AMR.