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In hematopoietic cell transplants, alloreactive T cells mediate the graft-versus-leukemia (GVL) effect. However, leukemia relapse accounts for nearly half of deaths. Understanding GVL failure requires a system in which GVL-inducing T cells can be tracked. We used such a model wherein GVL is exclusively mediated by T cells that recognize the minor histocompatibility antigen H60. Here we report that GVL fails due to insufficient H60 presentation and T cell exhaustion. Leukemia-derived H60 is inefficiently cross-presented whereas direct T cell recognition of leukemia cells intensifies exhaustion. The anti-H60 response is augmented by H60-vaccination, an agonist αCD40 antibody (FGK45), and leukemia apoptosis. T cell exhaustion is marked by inhibitory molecule upregulation and the development of TOX + and CD39 − TCF-1 + cells. PD-1 blockade diminishes exhaustion and improves GVL, while blockade of Tim-3, TIGIT or LAG3 is ineffective. Of all interventions, FGK45 administration at the time of transplant is the most effective at improving memory and naïve T cell anti-H60 responses and GVL. Our studies define important causes of GVL failure and suggest strategies to overcome them.

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Background: As the cost of care for patients with specific diagnoses becomes fixed, hospitals must develop systems to reduce length of stay and optimize the utilization of hospital resources while maintaining a high quality of care. The goal of this study is to evaluate the implementation and efficacy of a system designed to reduce average length of stay on a vascular surgery service. Study Design: To effectively reduce our average length of stay we restructured patient rounds, implemented multidisciplinary rounds, introduced clinical pathways to post-operative care, and expanded outpatient management of post-operative patients. 1697 adult vascular surgery patients discharged while under the medical direction of a vascular surgeon between 7/1/2013 and 6/30/2016 were included in the study. Results: Improving communication with critical staff and utilizing procedural space outside of the main operating rooms led to a 2.8-day reduction in length of stay (10.8 vs 8.0, P < 0.001). There was a trend toward a reduction in 30-day readmission rate (12% vs. 10%, respectively; P = 0.01) and no significant difference in case-mix index as a measure of illness severity (2.5 vs. 2.4, respectively; P = 0.15). Length of stay reductions were heterogeneous among the types of vascular disease studied, with greater improvements seen in patients undergoing lower extremity amputation, lower extremity angiogram, and endovascular aneurysm repair for non-ruptured abdominal aortic aneurysm. Less pronounced differences were observed in patients undergoing carotid artery endarterectomy/stenting and lower extremity bypasses. Conclusions: Restructuring team rounds and instituting a multidisciplinary approach to discharge planning produced significant reductions in length of stay without a deleterious effect on patient care that may impact hospital profitability.

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