ALBERT

Description: Background: There is compelling evidence that physical activity positively influences quality of life (QoL), and health-related outcomes including improved muscle mass and physical functioning in cancer pts. SCT pts however have unique barriers to exercise including isolation, restriction of activities, and treatment toxicity. In the early post SCT period, pts describe worsening fatigue, physical capacity and QoL. We sought to determine whether a partially supervised exercise intervention early post SCT would address these issues. Our primary objective was to determine the feasibility of delivering such an intervention at our institution. Secondary objectives were to assess changes as a result of the intervention in QoL, muscle mass and physical functioning. Methods: From Aug 2015-Jun 2016, we conducted a prospective single-arm study to evaluate feasibility of a 12 week partially supervised exercise program (1 supervised, 2 unsupervised sessions/week) for alloSCT pts with hematologic malignancies. The program consisted of 3 progressive endurance (stationary bike, walking) and 2 resistance training sessions/week, from hospital discharge (D/C) to Day (D) 100. Feasibility was defined as ability to recruit 〉65% of eligible pts, ≥70% retention and ≥70% adherence. Secondary outcomes were measured pre SCT (T0), at D/C (T1) and D100 (T2) and included QoL, muscle strength, mobility, aerobic fitness and body composition. Changes from T0 to T1 and T1 to T2 were compared using a paired sample t-test. Results: Of 43 consecutive alloSCT pts assessed for eligibility, 30 (70%) entered the study: 17 male (57%), median age 48 yrs (range 19-66 yrs). Transplants characteristics were: related 6; unrelated 24; myeloablative 23; reduced intensity 7. At baseline, SCT comorbidity index was 0 in 43%, 1-2 37%, ≥ 3 20%. Pts self-reported exercising enough to break a sweat (Godin et al) never 60%, sometimes 33%, often 7%. Median hospitalization was 29d (range 15-141); 9 pts developed grade II-IV acute graft-versus-host disease (skin 7, gut 5, liver 1). Overall retention to D100 was 80% (Figure 1). Two pts had complications during hospitalization and did not enter the program. Of the 24 pts who entered the program, adherence was 72% for supervised and 89% for unsupervised sessions. Logistics with scheduling around multiple medical appointments in the early post SCT period were the most common reasons for non-adherence. Other reasons included nausea, fatigue and weakness. One pt developed exercise-induced atrial fibrillation in week 3 requiring cessation of exercise. When comparing secondary outcomes from T0 to T1 (Table 1), pts had significantly decreased muscle strength (grip strength, 30-second chair stand), mobility (timed up-and-go [TUG]) and aerobic capacity (6-min walk test [6MWT]). At T2 after completion of the program, these measures all increased significantly when compared to T1. Global QoL scores on the EORTC measure decreased from T0 to T1 (P=.011) and were significantly improved by T2 (P

Description: Introduction: Heparin-induced thrombocytopenia (HIT) is a syndrome in which anti-platelet factor 4/heparin antibodies (HITab) and thrombocytopenia develop after heparin exposure. While HIT is an established risk factor for arterial and venous thromboses, HITab, in the absence of thrombocytopenia, may also be a prothrombotic risk factor. As patients with chronic kidney disease on hemodialysis are chronically exposed to heparin, we hypothesized that the presence of HITab may contribute to the high rates of thrombotic disease and mortality in these patients. Patients and methods: We analyzed data from the CHOICE study, a prospective cohort study of incident dialysis patients. Clinical data were available from medical record review. Arterial cardiovascular events and events of vascular access occlusion were validated by chart review and adjudication. Venous thromboembolic events were defined by ICD-9 codes. Thrombocytopenia was defined as a platelet count 50% decline from a previous platelet count. Median duration of follow-up is 2.7 years. We measured HITab using a commercial ELISA assay in stored serum obtained 6 months after cohort enrollment of 740 participants (596 on hemodialysis, 144 on peritoneal dialysis). ELISA results were corrected for inter-plate variability. A positive HITab test associated with thrombocytopenia in the subsequent three months was considered compatible with HIT. We used techniques of logistic regression and of survival analysis with adjustment for potential confounders in our analyses. Results: 10.3% of all patients were positive for HITab at six months. HITab positivity was not associated with thrombocytopenia. HITab did not predict subsequent outcomes including cardiovascular (hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.65–1.41), vascular access occlusive (HR 0.82, CI 0.40–1.71), or venous thromboembolic events (HR 1.39, CI 0.17–11.5) and did not predict mortality (HR 1.00, CI 0.66–1.53). 9 patients (1.2%) had results compatible with HIT (thrombocytopenia + HITab). 1 patient with HIT (0.13%) had venous thrombosis yielding a hazard ratio of 13.7 (CI 1.63–115.5) for HIT and thrombosis. Conclusions: HITab seropositivity after six months of dialysis is frequent, but is not associated with thrombocytopenia. In end-stage renal disease patients treated by dialysis HITab seropositivity in the absence of thrombocytopenia is not an independent risk factor for cardiovascular morbidity or mortality. However, HIT may occur in this patient population and is associated with thrombosis.

Description: Abstract 4498 Dectin-1 is a C-type lectin receptor that recognizes b-1,3-glucan, and plays an important role in antifungal immunity. The recently discovered dectin-1 Y238X polymorphism, which results in “loss-of-function” has been shown associated with increased Candida colonization of stem cell transplantation (SCT) recipients. Besides its role in antifungal immunity Dectin-1 exhibits a broader function in immunity. Stimulation of Dectin-1 with β-glucan affects antigen presentation, modulates T-lymphocytic (CD4+, both Th1 and Th17, and CD8+) and B-lymphocytic responses, and induces cytokine production including interleukin (IL) 10, IL-12 and IL-23. These specific T-cell responses and cytokines are of particular interest in SCT because they are involved in graft-versus-leukemia (GvL) effects as well as in the pathogenesis of graft-versus-host disease (GvHD). Therefore we now performed a retrospective study in 140 patients on the impact of the Y238X polymorphism on the outcome of myeloablative T cell-depleted matched related SCT. The allele frequency of the Y238X polymorphism was 6.6%, with 10.7% of patients and 15.7% of donors bearing the polymorphism. All were heterozygous and at least one polymorphism was present in 28 of 140 (20%) patient-donor pairs. We found no impact of the polymorphism on the occurrence of acute and chronic GvHD, non-relapse and relapse related mortality, nor disease-free and overall survival. Interestingly, patients from patient-donor pairs bearing the wild-type allele who were colonized with Candida had an increased incidence of acute GvHD compared to non-colonized patients (41.9% vs. 20.4%, OR=2.6 95%CI:1.02-6.58, P=0.04). However, this seemed to be the other way round for patients from pairs with the Y238X polymorphism (23.5% colonized vs. 30% not colonized, OR=0.7, ns). Therefore we hypothesize that the loss-of-function of dectin-1 increases colonization through deficient mucosal immunity, but prevents inflammatory complications resulting from colonization (Figure 1). This might explain the lack of an effect of the Dectin-1 Y238X polymorphism on outcome measures of SCT. Figure 1: Simplified hypothesis on the role of dectin-1, polymorphism Y238X, and Candida colonization on acute GvHD and possibly GvL. Figure 1:. Simplified hypothesis on the role of dectin-1, polymorphism Y238X, and Candida colonization on acute GvHD and possibly GvL. In case of Candida colonization (left) activation of the dectin-1 receptor influences immune responses and allo-reactivity increasing the incidence of acute GvHD. In the presence of the loss-of-function polymorphism Y238X (right), although Candida colonization is increased, due to the loss-of-function of dectin-1, no changes in the allo-reactive T-cell responses occur. Disclosures: No relevant conflicts of interest to declare.