Pharmacodynamics of Rituximab in Kidney Allotransplantation

Genberg, Helena; Hansson, A.; Wernerson, Annika; Wennberg, Lars; Tydén, G

doi:10.1111/j.1600-6143.2006.01497.x

Cited by 156 publications

(141 citation statements)

References 26 publications

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“…A more sensitive analytical method may have shown closer correlations with disease activity. In addition, rituximab results in the reduction of CD20-positive B cells in tissues as well as in blood (36,37), which may not be complete in tissues (38,39). Certainly, tissue B cell repopulation can occur prior to detectable return to the peripheral blood (20).…”

Section: Discussionmentioning

confidence: 99%

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

323

214

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Objective. B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as retreatment biomarkers.Methods. Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used.Results. All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P ‫؍‬ 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m 2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received >2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of lateonset neutropenia, which were attributed to rituximab.Conclusion. Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment.

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Section: Discussionmentioning

confidence: 99%

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

323

214

View full text Add to dashboard Cite

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“…Darabi et al (30) suggested that regularly scheduled TPE did not diminish the immunosuppressive effects of RIT due to the rapid effects of RIT on circulating CD20þ in a study with two thrombocytopenic purpura patients who were given RIT 24-36 hours before TPE. In renal or liver transplant recipients, peripheral CD20þ also rapidly disappeared within 48-72 hours after RIT infusion (25,31).…”

Section: Discussionmentioning

confidence: 99%

“…Several previous studies revealed that the effect of RIT on B cells in peripheral blood was very rapid, eliminating cells within 48-72 hours, and persisted for several months in transplant recipients (25). Furthermore, most data indicate that a single dose of RIT, as opposed to repeated doses, is sufficient for sustained suppression of B cells in peripheral blood (5,9,25,26). Consequently, repeated dosing of RIT may be unnecessary and may increase the risk of serious infection due to prolonged hypogammaglobulinemia.…”

Section: Discussionmentioning

confidence: 99%

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

Song

Lee

Hwang

et al. 2016

American Journal of Transplantation

111

124

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ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest singlecenter experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n ¼ 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.

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“…(4,5) and also organ transplantation (6)(7)(8)(9)(10)(11)(12)(13)16). Rituximab is used in sensitized organ-transplant patients to decrease preformed anti-HLA alloantibodies (9), in patients with a donor-specific-positive crossmatch on the day of transplantation (10), or to treat antibody-mediated allograft rejection in either its acute or chronic form (6,8,13,14).…”

Section: Introductionmentioning

confidence: 99%

Incidence and Predictive Factors for Infectious Disease after Rituximab Therapy in Kidney‐Transplant Patients

Kamar

Milioto²,

Puissant‐Lubrano

et al. 2010

American Journal of Transplantation

169

102

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(1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. The incidence of bacterial infection was similar between the two groups, whereas the viralinfection rate was significantly lower, and the rate of fungal infection was significantly higher in the rituximab group. Nine out of 77 patients (11.68%) died after rituximab therapy, of which seven deaths (9.09%) were related to an infectious disease, compared to 1.55% in the controls (p = 0.0007). In the whole population, the independent predictive factors for infectioninduced death were the combined use of rituximab and antithymocyte-globulin given for induction or antirejection therapy, recipient age, and bacterial and fungal infections. After kidney transplantation, the use of rituximab is associated with a high risk of infectious disease and death related to infectious disease.

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Pharmacodynamics of Rituximab in Kidney Allotransplantation

Cited by 156 publications

References 26 publications

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

Incidence and Predictive Factors for Infectious Disease after Rituximab Therapy in Kidney‐Transplant Patients

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