High Response Rate and Corticosteroid Sparing with Arsenic Trioxide-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Chronic graft-versus-host disease (cGVHD) occurs in 20% to 50% of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS) remain the first-line therapy but have suboptimal efficacy and carry a risk of long-term side effects. New agents with a better safety profile and higher efficacy are urgently needed. This study aimed to evaluate the efficacy and safety of a first-line combination of arsenic trioxide (ATO) and CS in adult patients with cGVHD requiring systemic therapy after first allo-HSCT for a hematologic disease. In this prospective national multicenter single-arm open-label Phase II study conducted in 5 university hospital centers in France, ATO was started within 10 days of CS at 1 mg/kg/day. Patients received 11 infusions per cycle of 28 days at a dose of .15 mg/kg per infusion. According to the clinical response and depending on the clinician's opinion, patients received 1 or 2 cycles of treatment. Cycles were separated by an 8- to 11-week interval from the first infusion of ATO. Patients were evaluated at 6 weeks, 14 weeks, 6 months, 9 months, and 12 months after the first ATO infusion, using the Chronic GVHD Activity Assessment Form A. The primary endpoint was preliminary efficacy based on the overall response rate (ORR; complete response [CR] or partial response [PR]) at 6 months. Response rates were estimated with 2-sided 95% exact confidence intervals (CIs). Twenty-one patients entered the study and received at least 1 ATO infusion (1 incomplete cycle for 1 patient, 1 complete cycle for 11 patients, and 2 complete cycles for 9). Six patients continued ongoing cyclosporine A (CsA) treatment after inclusion, and 4 other patients resumed CsA treatment during the study. The ORR at 6 months was 75.0% (95% CI, 50.9% to 91.3%), with CR in 35% and PR in 40%. Failure-free survival was 90.0% (95% CI, 65.6% to 97.4%) at 6 months and 65.0% (95% CI, 40.3% to 81.5%) at 12 months. The progression-free survival rate was 95.0% (95% CI, 69.5% to 99.3%) at 6 months and 83.8% (95% CI, 57.7% to 94.5%) at 12 months. The mean CS dose was decreased by 74.6 ± 32.7% from baseline to the 6-month visit and by 91.0 ± 14.6% from baseline to the 12-month visit. CS was definitively stopped in 30.0% of patients at the 6-month visit and in 47.4% at the 12-month visit. Two patients died, at 7 months and 12 months after the first ATO infusion from causes unrelated to ATO. One patient withdrew because of transient hepatotoxicity. The first-line combination of ATO and CS was associated with a high clinical response rate and rapid CS sparing in cGVHD after previous allo-HSCT.

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.