Başkent Üniversitesi Yayınları

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    Treatment of Antibody-Mediated Rejection in Kidney Transplant Recipients: A Single-Center Experience With a Bortezomib-Based Regimen
    (Başkent Üniversitesi, 2012-12) Nigos, Janice G.; Sureshkumar, Kalathil K.; Ko, Tina Y.; Marcus, Richard J.; Hussain, Sabiha M.; Nath, Parineesha; Arora, Swati
    Objectives: Antibody-mediated rejection after kidney transplant is less responsive to conventional antirejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomib-based regimen in patients with severe antibody-mediated rejection. Materials and Methods: A retrospective chart review was performed on patients with biopsy-proven antibody-mediated rejection after kidney transplant at our institution over 12 months. Diagnosis of antibody-mediated rejection was made on the basis of positive peritubular capillary C4d staining along with either histologic evidence of acute rejection or positive donor-specific antibody titers. Treatment for antibody-mediated rejection included plasmapheresis, intravenous immunoglobulin, steroids, single-dose rituximab (375 mg/m2) along with bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. Antibody-mediated rejection was diagnosed in 6 patients. Patients received induction with either alemtuzumab (n=4) or rabbit-antithymocyte globulin (n=2) and were maintained on a tacrolimus/mycophenolate mofetil/early steroid withdrawal protocol. Results: Four of 6 patients responded to treatment. Patients had stable kidney function during follow-up (median 14 months) after bortezomib therapy. Conclusions: In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific antibody titers and stable renal function in patients experiencing severe antibody-mediated rejection.
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    Effective Therapy for Acute Antibody-Mediated Rejection With Mild Chronic Changes: Case Report and Review of the Literature
    (Başkent Üniversitesi, 2012-08) Osama Gheith,; Ibraheim, Mona; Saied, Tarek; Muzeirei, Ibraheem; Al-Waheeb, Salah; Nair, Prasad; Halim, Medhat; Nampoory, Narayanan; Al-Otaibi, Torki
    To reduce the long-term toxicities of immuno­suppressant drugs, corticosteroid-sparing and calcineurin-inhibitor–sparing immunosuppression protocols have become increasingly popular in managing kidney transplant recipients. The most vexing clinical condition caused by antibodies in organ transplants is antibody-mediated rejection. Limitations of the current antibody-mediated rejection therapies include (1) antibody-mediated rejection reversal tends to be gradual rather than prompt, (2) expense, (3) rejection reversal rates below 80%, (4) common appearance of chronic rejection after antibody-mediated rejection treatment, and (5) long-term persistence of donor specific antibodies after therapy. Because these limitations may be due to a lack of effects on mature plasma cells, the effects of bortezomib on mature plasma cells may represent a quantum advance in antihumoral therapy. Our experiences represent the first clinical use of bortezomib as an antihumoral agent in renal allograft recipients in Kuwait. We present 2 cases with resistant-acute antibody-mediated rejection to the standard therapies that were managed successfully with bortezomib.