Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes.
There is limited evidence for a negative impact of preformed, donor-specific HLA antibodies (DSA) identified by cross-matching on outcomes after liver transplantation. Three recent studies have suggested an association between preformed DSA detected by Luminex and reduced graft or recipient survival in liver transplant cohorts with a high prevalence of hepatitis C. This study investigated the impact of preformed DSA identified by Luminex in the Scottish liver transplant population. All recipients of liver transplants in Scotland between 2007 and 2015 with samples available for day of transplant antibody testing and donor HLA typing were included (n=459); 96% of the cohort were white and 19% had a primary diagnosis of hepatitis C. The median follow-up time was 36 months. Preformed DSA were detected in 88 recipients. In multivariate analysis, preformed DSA with a median fluorescent intensity ≥10 000 were associated with recipient mortality at 1 year. There was no association between DSA and overall graft or recipient survival. This study adds to the growing body of evidence supporting a detrimental impact of preformed, high-level DSA in a subset of liver transplant recipients by identifying an association in an ethnically and demographically distinct liver transplant population.
To investigate an increased frequency of positive direct (DAT) and indirect (IAT) antiglobulin tests in bone marrow transplant (BMT) patients who received intravenous immunoglobulin (IVIG), serologic testing was performed weekly on blood samples from 94 consecutive BMT patients. Group 1 (47 patients) did not receive IVIG. Group II (47 patients) received high-dose IVIG as prophylaxis for cytomegalovirus infections. Before transplantation no alloantibodies were found in the serums of 92 patients and anti-E was found in the serums of two patients. DATs were negative in all patients before BMT. Four percent of Group I had a positive IAT and 13 percent had a positive DAT. In contrast, 25.5 percent of Group II patients had a positive IAT and 49 percent had a positive DAT, usually within 1 week after initiation of IVIG therapy (p less than 0.001). Antibodies identified in serums and eluates of patients in Group I were anti-A and anti-B. Antibodies identified in serums and eluates of patients in Group II were anti-A, -B, -D, and -K. Twenty-one lots of IVIG were tested and antibodies identified were anti-A, -B, -D, and -K. The data suggest that the higher frequency of positive serologic tests in Group II was due to passively acquired antibodies from high-dose IVIG.
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