Infusion of select leukemia-reactive TCR Vbeta+ T cells provides graft-versus-leukemia responses with minimization of graft-versus-host disease following murine hematopoietic stem cell transplantation

AbstractT-cell receptor (TCR) Vbeta-expression analysis by complementarity-determining region 3 (CDR3)-size spectratyping can identify the reactive populations in an immunologic response. This analysis was used in this study to characterize the Vbeta responses of C57BL/6 (B6) CD4+ and CD8+ T cells directed to either alloantigen (against [B6xDBA/2]F1; anti-H2d) or the syngeneic myeloid leukemia MMB3.19. Vbeta families exhibiting reactivity to the leukemia cells were then enriched for and administered in both syngeneic and allogeneic hematopoietic stem cell transplantation (HSCT) models to assess in vivo graft-versus-leukemia (GVL) potential. In syngeneic transplants, enrichment for pools of selected Vbeta families (Vbeta7, -11, and -13) of T cells or for a single Vbeta family (Vbeta7) of CD4+ T cells conveyed a beneficial GVL response to the recipients. Furthermore, in the haploidentical allogeneic model, both Vbeta6,7-enriched donor B6 T cells and Vbeta7-enriched CD4+ T cells exhibited significant GVL responses with concomitant minimization of graft-versus-host disease (GVHD) development compared with equal numbers of unfractionated T cells. These results suggest that CDR3-size spectratype analysis of and subsequent selection from donor T-cell repertoires can be an effective approach to separate GVL and GVHD potential following allogeneic HSCT.Biol Blood Marrow Transplant 2001;7(4):187-96

Bilateral radial artery pseudoaneurysms associated with bilateral ulnar artery atresia: a case report.

Pseudoaneurysms of the radial artery are uncommon and most often localized in an area of penetrating vascular trauma or iatrogenic injury. Hypoplasia of the ulnar artery is even more rare. We report a case of bilateral radial artery pseudoaneurysms associated with complete absence of any ulnar contribution to the vascularity of the hand. A patient presented with bilateral tender masses adjacent to the anatomic snuff boxes that interfered with hand function. After confirming that these masses were bilateral radial artery pseudoaneurysms, resection of the pseudoaneurysms and microscopic reconstruction of the arterial segments preserved vascular integrity of the hands and provided relief of the patient\u27s pain

TCT-804 Outcomes of Trans-Carotid TAVR in a high-Volume Center

Background Although the preferred route for transcatheter aortic valve replacement is through the femoral artery, alternatives remain necessary for patients with obstructive iliofemoral disease. Our valve team has developed a large experience using the carotid artery as a primary alternative vascular access approach for transcatheter aortic valve replacement (TAVR). We aim to compare short-term outcomes by access route in a single-center, high-volume, transcarotid (TC) TAVR program. Methods All patients undergoing TAVR between September 2012 and September 2018 were included in the study. Baseline demographics and outcomes were obtained from data our institution submitted in compliance with TVT (Transcatheter Valve Therapy) reporting and are supplemented by individual chart review. Results Overall, 1,153 commercial TAVR procedures were completed during the study period. Of these, 976 (85%) were transfemoral (TF), 105 (9%) were TC, and 72 (6%) were other (53 transapical, 14 transaxillary, 5 transaortic). TF patients had lower Society of Thoracic Surgeons (STS) scores (6.0% vs. 7.1% vs. 8.3%), peripheral vascular disease (24% vs. 88% vs. 72%), and cerebral vascular disease (11% vs. 17% vs. 32%) compared with TC and other patients, respectively (p \u3c 0.001). Combined in-hospital and 30-day mortality was 2.6% for the TF cohort versus 3.8% for TC (p = 0.36) and 13.9% for other (p \u3c 0.001). The stroke rate at 30 days was 3.7% for TF versus 3.8% for TC and 4.2% for other access routes (p = 0.98) (Table). Conclusion TAVR can be safely performed from the TC access route at a high-volume center with similar in-hospital and 30-day mortality and stroke rates compared with TF patients. Mortality was significantly increased, however, in patients treated with other alternative access routes

Antiviral Responses following L-Leucyl-L-Leucine Methyl Esther (LLME)-Treated Lymphocyte Infusions: Graft-versus-Infection without Graft-versus-Host Disease

Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative therapy for many disorders, it is associated with significant morbidity and mortality, which can be related to graft-versus-host disease (GVHD) and the immunosuppressive measures required for its prevention and/or treatment. Whether the immunosuppression is pharmacologic or secondary to graft manipulation, the graft recipient is left at increased risk of the threatening opportunistic infection. Refractory viral diseases in the immunocompromised host have been treated by infusion of virus-specific lymphotyces and by unmanipulated donor lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a compound that induces programmed cell death of natural killer (NK) cells, monocytes, granulocytes, most CD8+ T cells, and a small fraction of CD4+ T cells. We have undertaken a study of the use of LLME-treated DLI following T cell-depleted allogeneic HPCT, specifically to aid with immune reconstitution. In this ongoing clinical trial, we have demonstrated the rapid emergence of virus-specific responses following LLME DLI with minimal associated GVHD. This paper examines the pace of immune recovery and the rapid development of antiviral responses in 6 patients who developed viral infections during the time period immediately preceding or coincident with the administration of the LLME DLI