Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells to specifically target B-lineage malignant cells in animal models and clinical trials, with efficient tumor cell lysis. However, in some cases, there has been insufficient persistence of effector cells, limiting clinical efficacy. We propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel approach to deliver the CD19-specific CAR, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells. Assessments were performed using in vitro myeloid or natural killer (NK) cell differentiation of human HSPCs transduced with lentiviral vectors carrying first and second generations of CD19-specific CAR. Gene transfer did not impair hematopoietic differentiation and cell proliferation when transduced at 1-2 copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive cells, with second-generation CAR including CD28 domains being more efficient in NK cells. Our results provide evidence for the feasibility and efficacy of the modification of HSPC with CAR as a strategy for generating multiple lineages of effector cells for immunotherapy against B-lineage malignancies to augment graft-versus-leukemia activity.

Radical cystectomy and urinary diversion with enhanced recovery protocol is a morbid surgery. The most common complication, cause of ER visit and readmission is yet infections. Further studies on methods to decrease these rates are underway.

UTI is a common complication and cause of readmission following radical cystectomy and urinary diversion. These infections are commonly caused by Gram-negative rods. High comorbidity index is an independent risk factor for postoperative UTI, but diversion type is not.

INTRODUCTION AND OBJECTIVES: Enhanced recovery after surgery (ERAS) protocol is designed to improve perioperative care and decrease hospital stay without increasing complications. We have previously shown ERAS facilitates bowel function recovery and shortens hospital stay after radical cystectomy (RC) without increasing hospital readmission rates within the first 30-days. We now evaluate our ERAS protocol for complications in the first 90 days following RC.METHODS: All patients who underwent open RC with the ERAS perioperative protocol from 5/12 to 08/14 were included in the study. The protocol focuses on avoiding bowel preparation and nasogastric tube, early feeding, nonnarcotic pain management and the use of cholinergic and u-opioid antagonists. Non-consenting and patients lost to follow-up were excluded. 90-day complications (Clavien-Dindo grading system), readmissions and emergency room (ER) visits were prospectively recorded and compared to a group of matched controls (non-ERAS) who underwent RC from 10/08 to 5/12 by the same surgeons. Controls were matched by: age, sex, smoking status, BMI, Charlson comorbidity index and pathology stage.RESULTS: A total of 169 consecutive patients (ERAS) and 108 controls (non-ERAS) were included in the study. The median ages of groups were 71.0 (ERAS) and 69.9 (controls). The 90-day major complication rate was 24.3%, and 22.2%; while the minor complication rate was 53.9% vs 57.4% for ERAS and controls respectively (p¼0.34). Furthermore, the median number of complications per patient was 1.0 and 2.0 for ERAS and controls (p¼0.29). The rate of Gastrointestinal (GI) complications (21.3 vs. 33.3%; p¼0.03) and wound complications (11.8% vs. 20.4%; p¼0.05) were both lower in ERAS. Finally, the 90-day readmission rate (29.6% vs 26.9%; p¼0.24) and ER visit rate (37.9% vs 35.2%; p¼0.20) were not different between ERAS and controls respectively. CONCLUSIONS: Our ERAS protocol does not increase overall complication rates, hospital readmissions or ER visits compared to matched non-ERAS patients 90-days following RC. Furthermore, ERAS significantly reduces the frequency of GI complications during the

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