Kreuter, Justin D.

A new allele, now named HLA‐C*02:138, was discovered during testing of a registry donor for possible stem cell transplantation.

BACKGROUND: Plasma transfusion is commonly performed for the correction of abnormal coagulation screening tests. The goal of this investigation was to assess the relationship between the dose of plasma administered and changes in coagulation test results in a large and diverse cohort of patients with varying levels of coagulation abnormalities and comorbid disease and in a variety of clinical settings. METHODS: In this single-center historical cohort study, all plasma transfusion episodes in adult patients with abnormal coagulation screening tests were extracted between 2011 and 2015. The primary outcome was the proportion of patients attaining normal posttransfusion international normalized ratio (INR ≤ 1.1) with secondary outcomes including the proportion of patients attaining partial normalization of INR (INR ≤ 1.5) or at least 50% normalization in pretransfusion values with respect to an INR of 1.1. RESULTS: In total, 6779 unique patients received plasma with a median (quartiles) pretransfusion INR of 1.9 (1.6–2.5) and a median transfusion volume of 2 (2–3) units. The majority (85%) of transfusions occurred perioperatively, with 20% of transfusions administered prophylactically before a procedure. The median decrease in INR was 0.4 (0.2–0.8). Complete INR normalization was obtained in 12%. Reductions in INR were modest with pretransfusion INR values <3. Patients receiving ≥3 units of plasma were more likely to achieve at least 50% normalization in INR than those receiving ≤2 units (68% vs 60%; P < .001). CONCLUSIONS: Changes in INR after plasma transfusion were modest at typically used clinical doses, particularly in those with less severely deranged baseline coagulation screening tests. Further studies are necessary to assess the relationships between plasma-mediated changes in INR and clinical outcomes.

BACKGROUND Platelet transfusion–refractoriness is a challenging and expensive clinical scenario seen most often in patients with hematologic malignancies. Although the majority of platelet transfusion–refractory cases are due to nonimmune causes, a significant minority are caused by alloimmunization against Class I human leukocyte antigens (HLAs) or human platelet antigens (HPAs). Such platelet transfusion–refractory patients can be effectively managed with appropriate antigen‐negative products. STUDY DESIGN AND METHODS Our institution has developed a diagnostic and management algorithm for the platelet transfusion–refractory patient with an early focus on identifying those cases caused by immune‐mediated factors. Using physical platelet cross‐matches to initially classify platelet transfusion–refractory patients as immune‐mediated or not, cross‐match–compatible inventory is then provided to immune‐mediated patients, whereas subsequent HLA (with or without HPA) testing is performed. RESULTS Our blood donor program performs Class I HLA typing of all repeat platelet donors to facilitate the identification of antigen‐negative platelet units (virtual cross‐matching) as well as the recruitment of HLA‐matched donors. The platelet transfusion–refractoriness algorithm realizes an initial net cost savings once two apheresis platelets are saved from use for each newly identified, immune‐mediated platelet transfusion–refractory patient. CONCLUSION An algorithm utilizing physical platelet cross‐matches, Class I HLA and HPA antibody testing, and upfront Class I HLA typing of platelet donors leads to overall resource savings and improved clinical management for platelet transfusion–refractory patients.

AbstractObjectiveHLA‐DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA‐DPB1 mismatches based on T‐cell epitope, avoiding non‐permissive mismatches may impact survival. We tested this hypothesis at a single academic institution.MethodsRetrospective HLA‐DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA‐A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T‐cell epitope matching algorithm, mismatch status was classified as permissive or non‐permissive.ResultsOf 153 donor‐recipient pairs, 22 (14.4%) were HLA‐DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non‐permissive mismatches. DPB1 mismatch increased risk of chronic graft‐versus‐host disease (cGVHD; RR 2.89 [1.19‐9.53], P=.016) compared with DPB1‐matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non‐permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non‐permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13‐2.44], P=.010 and RR 1.97 [1.10‐3.59], P=.024, respectively).ConclusionIn this single‐center study, HLA‐DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.

Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA‐TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA‐TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA‐TMA since transplant. Thirty‐three patients diagnosed with TA‐TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All‐cause day‐30 and day‐100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P‐value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30‐day and 100‐day all‐cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P‐value = 0.25 and 0.08, for 30‐ and 100‐day all‐cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA‐TMA. The overall efficacy of PE is poor; however, patients who present with TA‐TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis 30:147–153, 2015. © 2014 Wiley Periodicals, Inc.