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This Week in NEJM: Mar 17, 2011

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In NEJM this week, researchers in the Netherlands, Switzerland, and Belgium present their findings from a trial of intermediate doses of cytarabine in the treatment of acute myeloid leukemia. High doses of the drug — 2,000 to 3,000 milligrams per square meter of body-surface area — is toxic, but result in higher rates of relapse-free survival than the conventional dose of 100 to 400 milligrams. The researchers split 860 patients into two groups; they gave one group an intermediate dose of 200 milligrams by continuous intravenous infusion for 24 hours during the first cycle of induction therapy and 1,000 milligrams by infusion for three hours twice daily during the second cycle; and they gave the high-dose group a dose-escalated regimen of 1,000 milligrams every 12 hours in the first cycle and 2,000 milligrams twice daily in cycle two. At a median follow-up of five years, the researchers saw no significant difference in survival or probability of relapse between the first and second groups, but the high-dose group did have more toxic side effects and prolonged hospitalization. "Induction therapy with cytarabine at the lower dose already produced maximal antileukemic effects for all response end points, suggesting a plateau in the dose–response relationship above this dose level," the authors write. "High-dose cytarabine results in excessive toxic effects without therapeutic benefit."

Also in NEJM this week, the University of Turin's Antonio Palumbo and Dana-Farber Cancer Institute's Kenneth Anderson say that the frequency of multiple myeloma in Western countries is likely to increase as the population ages. However, survival has been enhanced by the recent addition of thalidomide, lenalidomide, and bortezomib to the treatment mix. "At diagnosis, regimens that are based on bortezomib or lenalidomide, followed by autologous transplantation, are recommended in transplantation-eligible patients," the authors write. "Combination therapy with melphalan and prednisone plus either thalidomide or bortezomib is suggested in patients who are not eligible for transplantation." Maintenance therapy with thalidomide or lenalidomide has been shown to improve progression-free survival, they add, but more follow-up is needed to determine overall survival.

The Scan

Single-Cell Sequencing Points to Embryo Mosaicism

Mosaicism may affect preimplantation genetic tests for aneuploidy, a single-cell sequencing-based analysis of almost three dozen embryos in PLOS Genetics finds.

Rett Syndrome Mouse Model Study Points to RNA Editing Possibilities

Investigators targeted MECP2 in mutant mouse models of Rett syndrome, showing in PNAS that they could restore its expression and dial down symptoms.

Investigators Find Shared, Distinct Genetic Contributors to Childhood Hodgkin Lymphoma

An association study in JAMA Network Open uncovers risk variants within and beyond the human leukocyte antigen locus.

Transcriptomic, Epigenetic Study Appears to Explain Anti-Viral Effects of TB Vaccine

Researchers report in Science Advances on an interferon signature and long-term shifts in monocyte cell DNA methylation in Bacille Calmette-Guérin-vaccinated infant samples.