Background This Phase 2 study tested the tolerability and efficacy of bortezomib combined with reinduction chemotherapy for pediatric patients with relapsed, refractory or secondary acute myeloid leukemia (AML). Correlative studies measured putative AML leukemia initiating cells (AML-LIC) before and after treatment. Procedure Patients with <400 mg/m2 prior anthracycline received bortezomib combined with idarubicin (12 mg/m2 days 1–3) and low-dose cytarabine (100 mg/m2 days 1–7) (Arm A). Patients with ≥400 mg/m2 prior anthracycline received bortezomib with etoposide (100 mg/m2 on days 1–5) and high-dose cytarabine (1 g/m2 every 12 hours for 10 doses) (Arm B). Results Forty-six patients were treated with 58 bortezomib-containing cycles. The dose finding phase of Arm B established the recommended Phase 2 dose of bortezomib at 1.3 mg/m2 on days 1, 4, and 8 with Arm B chemotherapy. Both arms were closed after failure to meet predetermined efficacy thresholds during the first stage of the two-stage design. The complete response (CR + CRp) rates were 29% for Arm A and 43% for Arm B. Counting additional CRi responses (CR with incomplete neutrophil recovery), the overall CR rates were 57% for Arm A and 48% for Arm B. The 2-year overall survival (OS) was 39 ± 15%. Correlative studies showed that LIC depletion after the first cycle was associated with clinical response. Conclusion Bortezomib is tolerable when added to chemotherapy regimens for relapsed pediatric AML, but the regimens did not exceed preset minimum response criteria to allow continued accrual. This study also suggests that AML-LIC depletion has prognostic value.

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Background and Purpose-Cigarette smoking is a risk factor for the formation and rupture of intracranial aneurysms. Few studies have examined predictors of resumption of cigarette smoking after a first episode of subarachnoid hemorrhage (SAH). Methods-Of 620 SAH patients treated between July 1996 and November 2002, we prospectively evaluated continued cigarette use in 152 smokers alive at 3 months. Univariate and multivariate logistic regression analyses were used to identify potential demographic, social, and clinical predictors of continued cigarette use, defined as smoking Ն1 cigarette per week in the month before follow-up. Results-Thirty-seven percent (56 of 152) resumed smoking after their SAH. Patients who continued smoking were younger, were more often black, had begun smoking at an earlier age, and had a higher frequency of prior alcohol or cocaine use and self-reported depression or anxiety than those who quit (all PϽ0.05 Key Words: alcohol drinking Ⅲ cerebral aneurysm Ⅲ cigarette smoking Ⅲ subarachnoid hemorrhage S ubarachnoid hemorrhage (SAH) affects Ϸ21 000 adults in North America each year. 1 Even with significant improvements in the medical and surgical management of SAH, case fatality rates remain between 30% and 50%, 2-5 and those who survive frequently report impaired quality of life (QOL) characterized by disruptive cognitive and emotional symptoms. 3 A recurrent episode of SAH occurs in Ϸ2% to 3% of patients each year after surgical or endovascular aneurysm repair, and this risk increases with time. 6,7 Cigarette smoking is an important modifiable risk factor for SAH. 2,8 -12 Tobacco use is also a risk factor for the formation of multiple 13 and larger 14 aneurysms and therefore may be a risk factor for recurrent SAH after aneurysm repair. 8 Although it is known that up to 60% to 70% of SAH patients smoke cigarettes, 12,13 few studies have examined how many of these patients resume smoking after their hemorrhage or why they return. One study found that the proportion of smokers decreased from 58% before SAH to 30% 4 to 7 years later. 15 To the best of our knowledge, no studies have specifically analyzed risk factors for smoking resumption after SAH.Identification of risk factors for continued cigarette use after SAH may allow more effective substance use interventions while patients are in the hospital and may ultimately decrease the risk of recurrent SAH and other cardiovascular events. For instance, multidisciplinary hospital-based intervention programs increase the frequency of smoking cessation after myocardial infarction, 16,17 which results in reduced long-term mortality. 18 In this study, we sought to determine the frequency of continued cigarette use 3 months after SAH and to identify risk factors for smoking resumption. Patients and Methods Patient Population and Baseline AssessmentSix hundred twenty-six SAH patients admitted consecutively to our Neurological Intensive Care Unit (NICU) between July 1996 and November 2002 were prospectively enrolled in the Columbia University SAH Outc...

The randomized controlled trial is the model against which research designs are judged. Concurrent with rising standards of evidence, however, is a trend toward greater inclusiveness in community-based research, exemplified by the Centers for Disease Control and Prevention-funded Prevention Research Centers, a nationwide network of academic-community partnerships engaged in community-based health promotion and disease prevention research. The Yale-Griffin Prevention Research Center developed a replicable process for devising randomized trials in the context of community collaboration. Several examples of trials developed this way and their interim results are provided.