High-dose AraC is essential for the treatment of ML-DS independent of postinduction MRD: results of the COG AAML1531 trial.

Myeloid leukemia in children with Down syndrome (ML-DS) is associated with young age and somatic GATA1 mutations. Because of high event-free survival (EFS) and hypersensitivity of the leukemic blasts to chemotherapy, the prior Children's Oncology Group protocol ML-DS protocol (AAML0431) reduced overall treatment intensity but lacking risk stratification, retained the high-dose cytarabine course (HD-AraC), which was highly associated with infectious morbidity. Despite high EFS of ML-DS, survival for those who relapse is rare. AAML1531 introduced therapeutic risk stratification based on the previously identified prognostic factor, measurable residual disease (MRD) at the end of the first induction course. Standard risk (SR) patients were identified by negative MRD using flow cytometry (<0.05%) and did not receive the historically administered HD-AraC course. Interim analysis of 114 SR patients revealed a 2-year EFS of 85.6% (95% confidence interval [CI], 75.7-95.5), which was significantly lower than for MRD- patients treated with HD-AraC on AAML0431 (P = .0002). Overall survival at 2 years was 91.0% (95% CI, 83.8-95.0). Twelve SR patients relapsed, mostly within 1 year from study entry and had a 1-year OS of 16.7% (95% CI, 2.7-41.3). Complex karyotypes were more frequent in SR patients who relapsed compared with those who did not (36% vs 9%; P = .0248). MRD by error-corrected sequencing of GATA1 mutations was piloted in 18 SR patients and detectable in 60% who relapsed vs 23% who did not (P = .2682). Patients with SR ML-DS had worse outcomes without HD-AraC after risk classification based on flow cytometric MRD.

Humanized zebrafish enhance human hematopoietic stem cell survival and promote acute myeloid leukemia clonal diversity.

Xenograft models are invaluable tools in establishing the current paradigms of hematopoiesis and leukemogenesis. The zebrafish has emerged as a robust alternative xenograft model but, like mice, lack specific cytokines that mimic the microenvironment found in human patients. To address this critical gap, we generated the first humanized zebrafish that express human hematopoietic-specific cytokines (GM-CSF, SCF, and SDF1α). Termed GSS fish, these zebrafish promote survival, self-renewal and multilineage differentiation of human hematopoietic stem and progenitor cells and result in enhanced proliferation and hematopoietic niche-specific homing of primary human leukemia cells. Using error-corrected RNA sequencing, we determined that patient-derived leukemias transplanted into GSS zebrafish exhibit broader clonal representation compared to transplants into control hosts. GSS zebrafish incorporating error-corrected RNA sequencing establish a new standard for zebrafish xenotransplantation that more accurately recapitulates the human context, providing a more representative cost-effective preclinical model system for evaluating personalized response-based treatment in leukemia and therapies to expand human hematopoietic stem and progenitor cells in the transplant setting.

Associations between dietary habits and risk factors for cardiovascular diseases in a Hong Kong Chinese working population--the "Better Health for Better Hong Kong" (BHBHK) health promotion campaign.

Diet and nutritional status have been shown to play pivotal roles in the occurrence of many chronic diseases. In this study, we examined the patterns of dietary habits and their relationships with risk factors for cardiovascular and chronic diseases in Hong Kong working populations. In April 2000, a 5-year territory-wide health promotion campaign supported by the Li Ka Shing Foundation was launched in Hong Kong by the Health InfoWorld of Hospital Authority. Between July 2000 and March 2002, 4841 Chinese subjects [2375 (49.1%) men and 2466 (50.9%) women, mean age: 42.4 +/- 8.9 years (median: 43.0 years, range: 17-83 years)] from the general working class were recruited. Subjects were randomly selected using computer generated codes according to the distribution of occupational groups. A dietary questionnaire was used to assess 6 core dietary habits: daily fruit intake, vegetable intake, fluid intake, sugary drinks, regularity of daily meals and number of dining out each day. Overall, men had a worse cardiovascular risk profile and less desirable dietary habits than women. Those who had more unhealthy dietary habits were more likely to be obese and current smokers. Using logistic regression analysis with the dietary habits as independent variables, we found that obesity, smoking and constipation were independently associated with various unhealthy dietary patterns. In conclusion, there were close associations between dietary habits and risk factors for cardiovascular diseases in Hong Kong. More effective community education about healthy lifestyle is required in Hong Kong.