Evaluating Adequacy of VTE Prophylaxis Dosing with Enoxaparin for Overweight and Obese Patients on an Orthopedic-Medical Trauma Comanagement Service.

OBJECTIVES: Venous thromboembolism (VTE) is a common nosocomial condition, developing frequently in overweight and obese patients. VTE prophylaxis with weight-based enoxaparin dosing may be more effective than the standard dosing regimen for overweight and obese patients; however, weight-based dosing is not practiced routinely. In this pilot study we sought to evaluate prophylactic anticoagulation regimens used for VTE prevention in overweight and obese patients on the Orthopedic-Medical Trauma (OMT) service to inform the need for modification of dosing practices. METHODS: This prospective, observational study evaluated the adequacy of current VTE prophylaxis practice at an academic tertiary center, including overweight and obese patients admitted during 2017-2018 to an OMT comanagement service. It included patients hospitalized for at least 3 days with a body mass index (BMI) of ≥25 and prescribed enoxaparin. Steady-state antifactor Xa trough and peak levels were monitored after three doses. Frequency of in prophylactic range (0.2-0.44) antifactor Xa levels and VTE events were compared by BMI groups and enoxaparin dosing using the χ2 test. RESULTS: There were 404 inpatients included: 41.1% were overweight (BMI 25-29), 43.4% were obese (BMI 30-39), and 15.6% were morbidly obese (BMI ≥40). A total of 351 patients (86.9%) received standard dose enoxaparin 30 mg 2 times per day (BID), and 53 patients received enoxaparin 40 mg BID or more. A number of patients (213; 52.7%) did not achieve prophylactic range antifactor Xa levels. A significantly higher number of patients in the overweight group achieved prophylactic range antifactor Xa compared with obese and morbidly obese groups (58.4% vs 41.7% and 33%, P = 0.002 and 0.0007, respectively). Morbidly obese patients treated with enoxaparin 40 mg BID or higher versus enoxaparin 30 mg BID had fewer VTE events (4% vs 10.8%, P = 0.18). CONCLUSIONS: The current practice of VTE enoxaparin prophylaxis may not be adequate for overweight and obese OMT patients. Further guidelines are needed to implement weight-based VTE prophylaxis in overweight and obese hospitalized patients.

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

BACKGROUND: Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. METHODS: We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. RESULTS: At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. CONCLUSION: Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. TRIAL REGISTRATION: Clinicaltrials.gov NCT00442130. FUNDING: NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.