We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P < .01). The ABA patients demonstrated a low rate of aGVHD, despite robust immune reconstitution, with 2 of 10 patients diagnosed with grade II-IV aGVHD before day +100, no deaths from infection, no day +100 TRM, and with 7 of 10 evaluable patients surviving (median follow-up, 16 months). These results suggest that costimulation blockade with abatacept can significantly affect CD4(+) T cell proliferation and activation post-transplantation, and may be an important adjunct to standard immunoprophylaxis for aGVHD in patients undergoing unrelated-donor HCT.
Metabolic syndrome is an increasingly common condition that can contribute to the development of type 2 diabetes and cardiovascular disease. 35 % of adults living in the United States meet the criteria for having metabolic syndrome, with that number being even higher in populations with health disparities. We describe a 'healthy lifestyles' program implemented at a free clinic serving a predominantly Hispanic cohort of low-income, uninsured individuals living in Providence, Rhode Island. The "Vida Sana/Healthy Life" (Vida Sana) program uses low literacy, language-appropriate materials and trained peers to educate participants about healthy lifestyles in a setting that also provided opportunities for social engagement. 192 of 126 (65.6 %) participants in Vida Sana completed 6 out of 8 sessions of the Vida Sana program over a 12-month period. At the completion of the program, nearly 90 % of Vida Sana participants showed an increase in their health literacy, and at least 60 % of participants decreased each of the risk factors (blood sugar, cholesterol, body mass index or waist circumference) associated with metabolic syndrome.
Plerixafor with granulocyte colony-stimulating factor (G-CSF) is effective for hematopoietic stem cell (HSC) mobilization in patients with non-Hodgkin Lymphoma and myeloma; however, labeling requires dosing 11 hours before apheresis. Pharmacodynamic studies show peak blood CD34(+) cell counts at 10 to 14 hours; limited data are available for later time points. To address the effect of afternoon plerixafor dosing on CD34(+) cell yields, we conducted a prospective clinical trial in myeloma patients undergoing stem cell collection. Thirty-one patients received plerixafor 17 hours before apheresis; blood CD34(+) cells were measured before the first plerixafor dose and 1, 3, and 17 ± 1 hours after treatment. The target HSC number (≥10 × 106 CD34(+) cells/kg) was collected from 22 subjects (73%) in 1 day and from all subjects within 3 days. Hematopoietic engraftment after transplantation and adverse events were similar to previous studies. Plerixafor given 17 hours before apheresis yields desired HSC collection efficiencies after induction treatment in myeloma patients.
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