Background: In pediatric renal transplantation late onset de novo DSA leading to antibody-mediated rejection (AMR) has a poor prognosis. Our disappointing results with IVIG, rituximab and plasmapheresis led us to include bortezomib in our regimen to try to eliminate plasma cells that produce DSA.
Methods: Seven pediatric renal transplant recipients with late onset de novo DSA development and biopsy-proven AMR received 3-4 weekly doses of bortezomib 1.3 mg/M2, in addition to rituximab at 375 mg/M2, IVIG at 2 grams/kg, and, in 4 of 6 cases, intermittent plasmapheresis. All patients had concomitant ACR. All patients received 3 days of pulse methylprednisolone (10 mg/kg/dose up to 1 gram). If ACR was graded Banff IIa or higher they received either rabbit anti-thymocyte globulin if they had not received that previously, or alemtuzumab. Serum creatinine and DSA titers, expressed as mean fluorescence intensity (MFI), were assessed before and after treatment. DSA titers were considered positive when MFI was > 1500. The DSA titer peaks were compared to the most recent DSA titer obtained from 1-10 months after completion of treatment.
Results: The average and standard deviation for MFI of class I DSA before treatment was 4594±3271 and for class II, 10524±8445. Treatment resulted in an average percent decrease of 91%±15% for class I DSA (range 56-100%) and 69%±33% for class II (range 10-100%). 6 of 7 patients had class I DSA with complete resolution of class I DSA in 3. All 7 patients had class II DSA; 1 had complete clearance of class II DSA and titers decreased for the remainder. The average creatinine before treatment was 3.6 ± 3.4 (range 1.43 to 11.73) and after treatment,1.3 ± 0.3 (range 0.96 to 1.73). None of the patients developed neuropathy or other serious adverse drug reactions.
Conclusion: Bortezomib can be safely utilized in late onset de novo DSA mediated AMR in pediatric renal transplant patients. Historically, late onset de novo DSA-mediated AMR has had a very poor outcome. Although this is not a controlled study, the excellent outcome of our patients suggests that inclusion of bortezomib for the treatment of AMR should be considered for pediatric patients and justifies placebo controlled trials testing the efficacy of bortezomib for AMR.
To cite this abstract in AMA style:Ghata J, Sindhwani P, Lewis T, Turman M. Treatment of Late Onset De Novo Donor Specific Antibody (DSA)-Mediated Pediatric Kidney Transplant Rejection with Bortezomib [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/treatment-of-late-onset-de-novo-donor-specific-antibody-dsa-mediated-pediatric-kidney-transplant-rejection-with-bortezomib/. Accessed November 19, 2017.
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