• Fifty percent of TA-GVHD cases occur in patients who would not be predicted to be at risk for TA-GVHD by current guidelines for blood irradiation.• Donor lymphocytes whose HLA antigens are all shared by the recipient dominate in TA-GVHD cases, particularly in immune-competent recipients.Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The clinicolaboratory features of TA-GVHD and the relative contributions of recipient and component factors remain poorly understood. We conducted a systematic review of TA-GVHD reports. The HLA relationship between donor and recipient was classified as D 5 0 when no donor antigens were foreign to the recipient vs D ‡ 1 when ‡1 donor antigen disparity occurred. We identified 348 unique cases. Criteria for component irradiation were met in 48.9% of cases (34.5% immune-compromised, 14.4% related-donor), although nonirradiated components were transfused in the vast majority of these (97.6%). Components were typically whole blood and red cells. When reported, component storage duration was £10 days in 94%, and 23 (6.6%) were leukoreduced (10 bedside, 2 prestorage, and 11 unknown). Among 84 cases with HLA data available, the category of D 5 0 was present in 60 patients (71%) at either HLA class I or II loci and was more common among recipients without traditional indications for component irradiation. These data challenge the historic emphasis on host immune defects in the pathogenesis of TA-GVHD. The dominant mechanism of TA-GVHD in both immunocompetent and compromised hosts is exposure to viable donor lymphocytes not recognized as foreign by, but able to respond against, the recipient. (Blood. 2015;126(3):406-414)

Background Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. Materials and Methods We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT). The objectives were to determine safety, feasibility and evidence of activity. Patients were treated at one of three dose levels (1 × 10 9 cells/m 2 , 3 × 10 9 cells/m 2 and 5 × 10 9 cells/m 2 ), given on day 1, 3 and 5 for a planned total of six monthly cycles. Results Twelve patients with lymphoma or multiple myeloma who relapsed after AHCT for relapsed/refractory disease were enrolled in this trial. The treatment was well tolerated, with minor toxicities restricted to acute infusional events, including fever, chills, nausea and fatigue. Two patients achieved a complete response (Hodgkin lymphoma and multiple myeloma), two patients had minor responses and one had clinical improvement on the trial. Conclusions Irradiated NK-92 cells can be administered at very high doses with minimal toxicity in patients with refractory blood cancers, who had relapsed after AHCT. We conclude that high dose NK-92 therapy is safe, shows some evidence of efficacy in patients with refractory blood cancers and warrants further clinical investigation.

This study was conducted to assess the prevalence and zoonotic potential of giardiasis in domestic ruminants. Prevalence of infection was 17.7% in sheep and 10.4% in cattle and was significantly higher in lambs and calves (35.6% and 27.7%, respectively). Naturally infected lambs released cysts intermittently for months. Giardia trophozoites from sheep had typical claw hammer-shaped median bodies and were successfully cultured in TYI-S-33 medium, and cytosolic, cytoskeletal, and membrane fractions exhibited protein profiles similar to human isolates (WB). Immunoblotting showed that sera from infected sheep recognized human Giardia, sera from patients with giardiasis recognized Giardia from sheep, and in both cases recognition involved antigenic proteins of similar molecular weight. Cyst output and clinical signs in ovine infection resemble human disease and the organisms infecting humans and ruminants are morphologically and antigenically similar. It is postulated that domestic ruminants may be a reservoir for human infection and vice versa, thus classifying giardiasis as a zooanthroponotic disease.

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