A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation.

BACKGROUND: Plasmapheresis is a desensitization method used prior to ABO-incompatible (ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking. METHODS: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January 2012 and October 2015. A single dose of rituximab (300 mg/m2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014 (RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015 (RO group, n = 30). RESULTS: The 6-, 12- and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively (P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications. CONCLUSIONS: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.

Immune Desensitization Allows Pediatric Blood Group Incompatible Kidney Transplantation.

BACKGROUND: Blood group incompatible transplantation (ABOi) in children is rare as pretransplant conditioning remains challenging and concerns persist about the potential increased risk of rejection. METHODS: We describe the results of 11 ABOi pediatric renal transplant recipients in the 2 largest centers in the United Kingdom, sharing the same tailored desensitization protocol. Patients with pretransplant titers of 1 or more in 8 received rituximab 1 month before transplant; tacrolimus and mycophenolate mofetil were started 1 week before surgery. Antibody removal was performed to reduce titers to 1 or less in 8 on the day of the operation. No routine postoperative antibody removal was performed. RESULTS: Death-censored graft survival at last follow-up was 100% in the ABOi and 98% in 50 compatible pediatric transplants. One patient developed grade 2A rejection successfully treated with antithymocyte globulin. Another patient had a titer rise of 2 dilutions treated with 1 immunoadsorption session. There was no histological evidence of rejection in the other 9 patients. One patient developed cytomegalovirus and BK and 2 others EBV and BK viremia. CONCLUSIONS: Tailored desensitization in pediatric blood group incompatible kidney transplantation results in excellent outcomes with graft survival and rejection rates comparable with compatible transplants.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption.

BACKGROUND: For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. METHODS: We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. RESULTS: Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. CONCLUSIONS: Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

Potent immunosuppression for ABO-incompatible renal transplantation may not be a risk factor for malignancy.

ABO-incompatible (ABOi) renal transplantation has been increasing, but malignant tumor is a troubling complication of kidney transplantation due to potent immunosuppression. Few previous studies, however, have demonstrated that potent immunosuppression for ABOi living-donor renal transplantation (LDRT) is a risk factor for malignancy. In the present research, data on 252 LDRT patients ftom 2003 to 2008 were retrospectively analyzed to clarify whether ABOi LDRT was associated with malignancy. A potent immunosuppressive regimen for ABOiLDRT consisted of splenectomy, cyclophosphamide, and double-filtration plasmapheresis to minimize the risk of antibody-mediated rejection, in addition to conventional immunosuppresssants including calcineurin inhibitor, prednisolone, and anti-CD25 monoclonal antibody. A total of 11 incidences of malignancy were observed during a median follow-up of 48 months. The incidence rates in ABO-compatible (ABOc; n = 189) and ABOi (n = 63) LDRT groups were 4.2 % (8/189) and 4.8 % (3/63), respectively. Kaplan-Meier survival analysis showed no statistical difference in event-free survival for malignancy between ABOc and ABOiLDRT groups (log-rank P = .73). Multivariable Cox regression analyses identified no associations of malignancy with ABOi LDRT or any immunosuppressant use. In conclusion, our investigation suggested that potent immunosuppression with splenectomy and cyclophosphamide for ABOi LDRT may not be a risk factor for malignancy.

Bridge to transplant experience: factors influencing survival to and after cardiac transplant.

OBJECTIVE: Balancing longer duration of mechanical circulatory support while awaiting functional recovery against the increased risk of adverse events with each day on support is difficult. Therefore, we investigated the complex interplay of duration of mechanical circulatory support and patient and device factors affecting survival on support, as well as survival after transplantation. METHODS: From December 21, 1991, to July 1, 2006, mechanical circulatory support was used in 375 patients as a bridge to transplantation, with 262 surviving to transplant. Implantable pulsatile devices were used in 321 patients, continuous flow was used in 11 patients, a total artificial heart was used in 5 patients, external pulsatile devices were used in 34 patients, and extracorporeal membrane oxygenation was used in 68 patients. Two time-related models were developed: (1) a competing-risks multivariable model of death on mechanical circulatory support, with modulated renewal for each sequential support mode; and (2) a model of death after transplant in which patient factors and duration of mechanical circulatory support were investigated as risk factors. RESULTS: Survival after initiating mechanical circulatory support, irrespective of transplantation, was 86% at 30 days, 55% at 5 years, and 41% at 10 years; survival was 94%, 74%, and 58% at the same time intervals, respectively, after transplantation in those surviving the procedure. Risk factors for death included longer, but not shorter, duration of mechanical circulatory support, use of multiple devices, global sensitization, and poor renal function. CONCLUSION: Initiating mechanical circulatory support early with a single definitive device may improve survival to and after cardiac transplantation. Early transplant, which avoids infection, sensitization, and neurologic complications, may improve bridge and transplant survival.