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This Week in NEJM: Apr 12, 2012

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In NEJM this week, Schrappe et al. report on outcomes for children and adolescents with acute lymphoblastic leukemia, who suffer a failure of remission-induction therapy. The team identified induction failure by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after treatment in 1,041 patients up to 18 years old. "Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement," the authors write. "An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25 percent or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia." Pediatric ALL with induction failure is highly heterogeneous, the team concludes.

In a related editorial, Texas Children's Cancer Center's Karen Rabin says the 80 percent cure rate for children with ALL is deceptive as children with "unfavorable features" like induction failure have a much lower cure rate. But studies like the one done by Schrappe et al. are shedding light on the heterogeneity of the disease. "A key finding is that the prognostic value of various clinical and biologic features of ALL at diagnosis also holds true within the microcosm of ALL induction failure," Rabin writes. "These data also highlight the complex interrelationship between disease biology and early treatment response — that is, inferior initial responses to therapy portend different outcomes within unique biologic subgroups." As this study shows, Rabin adds, "sophisticated risk stratification" of patients with childhood ALL may lead to improved survival rates for patients with different subtypes of the disease.

Finally in NEJM this week, an international team of researchers report on the efficacy of olaparib maintenance therapy in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. The team randomly assigned 265 patients, who had received two or more platinum-based regimens and had had a partial or complete response to those regimens, to receive either olaparib or placebo. They found that progression-free survival was significantly higher in the olaparib group, though there was no significant difference in overall survival between the two groups.

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