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• W2327774670 abstract "We appreciate the letter by Jordan et al. in correspondence to our study (1) and study by Alachkar et al. (2) investigating the effects of high-dose intravenous immunoglobulin (IVIg) and a single dose of rituximab or IVIg alone in highly sensitized patients on the deceased-donor waiting list. Although the letter by Jordan et al. claimed that their published studies were not referenced in our study, it was very clear that our study was solely based on the published experience of Dr. Jordan using high-dose IVIg alone (3) or IVIg with rituximab (4, 5) referenced in our article (1). As previously outlined in our article, we have attributed the sharp differences in our findings compared with that of the Cedar Sinai group to patient selection. Our patient’s degree of sensitization was significantly higher with a median class I calculated panel reactive antibody (CPRA) of 99% (98%–100%) and class II CPRA of 98% (90%–100%) compared with a mean class I complement-dependent cytotoxicity PRA of 77%±19% in their initial study (4) and flow cytometry class I PRA of 80%±26% and class II PRA of 60%±29% in their follow-up study (5). Consistent with our results, a small study from the University of North Carolina using a similar desensitization protocol of IVIg and rituximab in five patients with a mean CPRA level of 94%±18% did not demonstrate an increased transplantation rate nor a significant decrease in anti–human leukocyte antigen (HLA) antibody levels (6). Furthermore, desensitization studies using high-dose IVIg alone by Alachkar et al. (2), by Machimoto et al. (7), and, most recently, by Nair et al. (8) have not demonstrated benefit in the reduction of anti-HLA antibodies. However, in all these three studies, patients’ PRA levels were more than 80% to 90%. The studies reported a lack of benefit in reducing PRA levels or increasing transplantation rates with a desensitization protocol with either high-dose IVIg alone or IVIg plus rituximab. The number of patients studied was small compared with the experience by the Cedar Sinai group. However, there seems to be a repeating pattern that patient selection is the key and such protocols may not be beneficial in highly sensitized patients on the deceased-donor waiting list with CPRA levels greater than 90%. Furthermore, in addressing some of the other issues raised by Jordan et al., we do agree that the goal of desensitization is to accomplish antibody reduction of unacceptable antigens to acceptable levels to allow for successful transplantation rates. As described previously in our review article (9), we report to UNet anti-HLA antibodies to HLA-A, HLA-B, HLA-DR, and HLA-DQ with mean fluorescence intensity (MFI) values of more than 5000 as unacceptable antigens. We removed the unacceptable antigens if MFI values decreased to less than 5000 after desensitization therapy. However, currently we do not perform desensitization treatment for highly sensitized patients on top of deceased-donor waiting list due to our unsuccessful experience, but patients with donor-specific anti-HLA antibody MFI values between 1000 and 5000 and flow cytometry T- and B-cell crossmatch channel shift values of 50 to 150 and 100 to 250, respectively, are accepted for transplantation using antithymocyte globulin and IVIg (1.5–2.0 g/kg) induction (9). We have previously reported excellent short-term graft survival without increase in antibody-mediated rejection in such patients with low titer donor-specific antibodies (10). We have to be very critical when evaluating the overall benefits of desensitization therapy with using high-dose IVIg alone or IVIg combined with rituximab in highly sensitized patients on the deceased-donor waiting list outside of randomized controlled trials. Where these therapies may not increase complication rates as a consequence of side effects from the treatments administered (11), they are associated with significant cost to the healthcare system. Unfortunately, there is not any randomized control study that has investigated the effects of different desensitization protocols in highly sensitized patients on the deceased-donor waiting list comparing with the control group without desensitization treatment but allowing kidney transplantation in donor-specific antibody–positive patients with lower MFI and flow cytometric crossmatch channel shift values with induction treatment including IVIg, which would be the ideal study design to answer this question instead of comparing retrospective outcomes of different transplant centers. Kwaku Marfo Enver Akalin Montefiore-Einstein Center for Transplantation Montefiore Medical Center Albert Einstein College of Medicine Bronx, NY" @default.
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• W2327774670 date "2013-03-27" @default.
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• W2327774670 title "Reply to “Defining the Benefits of Desensitization Therapy”" @default.
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• W2327774670 doi "https://doi.org/10.1097/tp.0b013e3182846013" @default.
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