To compare single-agent gemtuzumab ozogamicin (GO) with best supportive care (BSC) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy. Patients and MethodsIn this trial, patients at least 61 years old were centrally randomized (1:1) to receive either a single induction course of GO (6 mg/m 2 on day 1 and 3 mg/m 2 on day 8) or BSC. Patients who did not progress after GO induction could receive up to eight monthly infusions of the immunoconjugate at 2 mg/m 2 . Randomization was stratified by age, WHO performance score, CD33 expression status, and center. The primary end point was overall survival (OS) by intention-to-treat analysis. ResultsA total of 237 patients were randomly assigned (118 to GO and 119 to BSC). The median OS was 4.9 months (95% CI, 4.2 to 6.8 months) in the GO group and 3.6 months (95% CI, 2.6 to 4.2 months) in the BSC group (hazard ratio, 0.69; 95% CI, 0.53 to 0.90; P = .005); the 1-year OS rate was 24.3% with GO and 9.7% with BSC. The OS benefit with GO was consistent across most subgroups, and was especially apparent in patients with high CD33 expression status, in those with favorable/ intermediate cytogenetic risk profile, and in women. Overall, complete remission (CR [complete remission] + CRi [CR with incomplete recovery of peripheral blood counts]) occurred in 30 of 111 (27%) GO recipients. The rates of serious adverse events (AEs) were similar in the two groups, and no excess mortality from AEs was observed with GO. ConclusionFirst-line monotherapy with low-dose GO, as compared with BSC, significantly improved OS in older patients with acute myeloid leukemia who were ineligible for intensive chemotherapy. No unexpected AEs were identified and toxicity was manageable.J Clin Oncol 34.

Aberrant promoter methylation of tumor suppressor genes has not been fully investigated in pediatric tumors. Therefore, we examined the methylation status of nine genes (p16 INK4A , MGMT, GSTP1, RASSF1A, APC, DAPK, RARb, CDH1 and CDH13) in 175 primary pediatric tumors and 23 tumor cell lines using methylation-speci®c PCR. We studied the major forms of pediatric tumors ± Wilms' tumor, neuroblastoma, hepatoblastoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma, retinoblastoma and acute leukemia. The most frequently methylated gene in both primary tumors and cell lines was RASSF1A (40, 86%, respectively). However, the rates of RASSF1A methylation in individual tumor types varied from 0 to 88%. RASSF1A methylation was tumor speci®c and was absent in adjacent non-malignant tissues. Methylation of the other genes was relatively rare in tumors and nonmalignant tissues (less than 5%). Neuroblastoma patients with methylation of RASSF1A were signi®-cantly older than patients without methylation (P=0.008). There was no relationship between methylation status and other clinico-pathologic parameters. We treated six cell lines lacking RASSF1A mRNA with 5-aza-2'deoxycytidine to examine the relationship between methylation and transcriptional silencing. In ®ve of six cell lines, restoration of RASSF1A mRNA was con®rmed by RT ± PCR. Our ®ndings indicate that aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many di erent forms of pediatric tumors.

Purpose Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m2 for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. Patients and Methods The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m2 per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m2 every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m2 every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. Results At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine. Conclusion HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.

Rupture of the free wall of the left ventricle (LV) is a catastrophic complication occurring in 4% of patients after myocardial infarction (MI) and in 23% of those who die of MI. Rarely the rupture is contained by an adherent pericardium creating a pseudo-aneurysm. This clinical finding calls for emergency surgery. If no ruptures are detectable and myocardium wall integrity is confirmed, we are in the presence of a true aneurysm, which can be treated by means of elective surgery. Differentiation between these two pathologies remains difficult. We report the case of a patient with a true aneurysm, initially diagnosed as pseudo-aneurysm at our institution; we have reviewed the literature on this difficult diagnosis and outlined characteristic findings of each clinical entity.

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As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

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