The PedAL/EuPAL Project: A Global Initiative to Address the Unmet Medical Needs of Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia.

The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40-50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed for these children. The Pediatric Acute Leukemia (PedAL) program is a strategic global initiative that aims to overcome the obstacles in treating children with relapsed/refractory acute leukemia and is supported by the Leukemia and Lymphoma Society in collaboration with the Children's Oncology Group, the Innovative Therapies for Children with Cancer consortium, and the European Pediatric Acute Leukemia (EuPAL) foundation, amongst others. In Europe, the study is set up as a complex clinical trial with a stratification approach to allocate patients to sub-trials of targeted inhibitors at relapse and employing harmonized response and safety definitions across sub-trials. The PedAL/EuPAL international collaboration aims to determine new standards of care for AML in a first and second relapse, using biology-based selection markers for treatment stratification, and deliver essential data to move drugs to front-line pediatric AML studies. An overview of potential treatment targets in pediatric AML, focused on drugs that are planned to be included in the PedAL/EuPAL project, is provided in this manuscript.

Power Up for Health: Pilot Study Outcomes of a Diabetes Prevention Program for Men from Disadvantaged Neighborhoods.

There is a significant evidence base for the Diabetes Prevention Program, a lifestyle intervention to prevent onset of type 2 diabetes among high-risk individuals; however, translation of this intervention for men has been challenging. This report presents outcomes of the pilot study of an adapted 16-week diabetes prevention program entitled " Power Up for Health." The study goal was to better engage men of color with prediabetes from disadvantaged neighborhoods of New York City. It was implemented at five different recreation centers located in predominantly low-income neighborhoods across New York City. The curriculum was facilitated by male lifestyle coaches only; one group was conducted in Spanish. Primary outcome was weight loss from baseline to 16 weeks. Other measures included lifestyle activities, depressive symptoms, and self-reported health status. Men ( N = 47) were screened by telephone. Of the 29 eligible men who began the program, 25 attended at least 4 sessions (52% non-Latino Black, 32% Latino, mean age 51.7 ± SD 9.9 years, mean body mass index 35 ± SD 6.9 kg/m2). End of program outcomes ( n = 23) varied by site and included a mean weight loss of 3.8% (9.7 lbs); 3 of the 5 sites had a mean weight loss of 5.6%, meeting the national goal of 5%-7%. Men ( n = 23) attended a mean of 11.6 of 16 sessions. Improvement in depressive symptoms, healthy eating and exercise, and health status were also seen. While recruitment was challenging with many lessons learned, the adapted men's diabetes prevention program shows promise of success for participants and their coaches.

Translation of the National Diabetes Prevention Program to Engage Men in Disadvantaged Neighborhoods in New York City: A Description of Power Up for Health.

The Diabetes Prevention Program (DPP) landmark randomized trial demonstrated that participants with prediabetes could reduce their risk for type 2 diabetes by 58% if they achieved 5%-7% weight loss through healthy eating and increasing physical activity. The National DPP (NDPP) is a group intervention based on the DPP and has been widely disseminated by the Centers for Disease Control and Prevention (CDC) and many healthcare institutions. While data show that the program is effective in diverse populations, enrollment among men from low-income and minority communities is low. Thus, the study piloted a novel adaptation focused on men living in disadvantaged neighborhoods. The study approach to adaptation and implementation used characteristics of participatory research, including input from an expert panel of African American and Latino leaders, ongoing consultation with an Advisory Panel, and focus groups with members of the target population. Discussions with these groups focused on male perspectives regarding health promotion and barriers and facilitators to participation in health programming for men. There was general agreement when reviewing ongoing pilot program implementation that the adapted program should have male-only groups with male coaches, as the Advisory Panel had originally suggested. The pilot programs were implemented at five New York City Department of Parks and Recreation sites in Harlem, the Bronx, and Brooklyn in 2015-2016.

Breast cancer incidence and the effect of cigarette smoking in heterozygous carriers of mutations in the ataxia-telangiectasia gene.

BACKGROUND: Mutations in the ataxia-telangiectasia (A-T) gene cause an autosomal recessive syndrome in homozygotes and compound heterozygotes and predispose female heterozygous carriers to breast cancer. No environmental agent has been previously shown to increase the risk of cancer for women who carry a mutated gene that predisposes to breast cancer. This study assesses the effect of cigarette smoking on the risk of breast cancer in A-T mutation carriers and determines age-specific and cumulative incidence rates for breast cancer among such carriers. METHODS: Clinical data were collected between 1971 and 1999 from blood relatives from 274 families of patients with A-T. The A-T mutation carrier status of 973 females was determined by molecular analysis of blood and tissue samples. The breast cancer rates in carrier smokers and nonsmokers were compared. Age-specific and cumulative breast cancer rates were also compared between carriers and noncarriers using Kaplan-Meier survival curves. RESULTS: The cumulative incidence through age 80 years was 80% for carriers who smoked and 21% for carriers who never smoked (P = 0.01). Six cases of breast cancer were diagnosed between ages 70 and 79 years among carriers who smoked. The cumulative breast cancer incidence among A-T mutation carriers was 43% by age 80 years, compared with 17% for noncarriers (P = 0.002). Carriers had new incident breast cancers at an annual rate of 1.4% from ages 65 through 79 years; for noncarriers the rate was 0.20%. CONCLUSIONS: A-T carrier females had an elevated risk of breast cancer, most pronounced at older ages, compared with noncarriers, and smoking increased this risk substantially.