The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of alltrans-retinoic acid (ATRA), anthracyclinebased chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification

Background and Purpose-Intracerebral hemorrhage (ICH) growth predicts mortality and functional outcome. We hypothesized that irregular hematoma shape and density heterogeneity, reflecting active, multifocal bleeding or a variable bleeding time course, would predict ICH growth. Methods-Three raters examined baseline sub-3-hour CT brain scans of 90 patients in the placebo arm of a Phase IIb trial of recombinant activated Factor VII in ICH. Each rater, blinded to growth data, independently applied novel 5-point categorical scales of density and shape to randomly presented baseline CT images of ICH. Density and shape were defined as either homogeneous/regular (Category 1 to 2) or heterogeneous/irregular (Category 3 to 5). Within-and between-rater reliability was determined for these scales. Growth was assessed as a continuous variable and using 3 binary definitions: (1) any ICH growth; (2) Ն33% or Ն12.5 mL ICH growth; and (3) radial growth Ͼ1 mm between baseline and 24-hour CT scan. Patients were divided into tertiles of baseline ICH volume: "small" (0 to 10 mL), "medium" (10 to 25 mL), and "large" (25 to 106 mL). Results-Inter-and intrarater agreements for the novel scales exceeded 85% (Ϯ1 category). Median growth was significantly higher in the large-volume group compared with the small group (PϽ0.001) and in heterogeneous compared with homogeneous ICH (Pϭ0.008). Median growth trended higher in irregular ICHs compared with regular ICHs (Pϭ0.084). Small ICHs were more regularly shaped (43%) than medium (17%) and large (3%) ICHs (PϽ0.001). Small ICHs were more homogeneous (73%) compared with medium (37%) and large (17%) ICHs (PϽ0.001). Adjusting for baseline ICH volume and time to scan, density heterogeneity, but not shape irregularity, independently predicted ICH growth (Pϭ0.046) on a continuous growth scale. Conclusions-LargeICHs were significantly more irregular in shape, heterogeneous in density, and had greater growth.Density heterogeneity independently predicted ICH growth using some definitions. Key Words: density Ⅲ growth Ⅲ intracerebral hemorrhage Ⅲ recombinant activated factor VII Ⅲ predictors Ⅲ shape I ntracerebral hemorrhage (ICH) is the most sinister stroke subtype with a high early mortality. 1,2 Despite this, there is convincing evidence that aggressive care can bring about meaningful recovery, even in the worst initial prognostic groups. 3,4 CT scanning remains the standard diagnostic technique for ICH. Hematoma growth occurs in Ͼ70% of patients on CT performed within 3 hours of symptom onset and independently predicts mortality and functional outcome. 5 Hemostatic therapy has been demonstrated to attenuate ICH growth in 2 pivotal studies of recombinant activated Factor VII administered within 4 hours of symptom onset. 6,7 In contrast, the clinical outcomes in these trials were discordant and the positive results were not replicated in the second, larger trial. 6,7 Attenuated hematoma growth has also been suggested in an acute blood pressure reduction trial. 8 Hence, hematoma growth is a key therapeu...