All-trans-retinoic acid as induction or maintenance treatment improves disease-free and overall survival as compared with chemotherapy alone and should be included in the treatment of acute promyelocytic leukemia.

Arsenic trioxide (As 2 O 3 ) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age > 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As 2 O 3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As 2 O 3 consolidation, 80% compared with 63% at 3 years (stratified logrank test, P < .0001). Survival, a secondary end point, was better in the As 2 O 3 arm, 86% compared with 81% at 3 years (P ‫؍‬ .059). Disease-free survival, a secondary end point, was significantly better in the As 2 O 3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As 2 O 3 consolidation to standard induction and consolidation therapy significantly improves event-free and diseasefree survival in adults with newly diagnosed APL. This trial was registered at clinicaltrials.gov (NCT00003934).

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We previously reported a benefit for alltrans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American Intergroup APL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) or ATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was con-

Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.

CCG-2961 incorporated 3 new agents, idarubicin, fludarabine and interleukin-2, into a phase 3 AML trial using intensivetiming remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification. Among 901 patients under age 21 years, 5-year survival was 52%, and event-free survival was 42%. Survival improved from 44% between 1996 and 1998 to 58% between 2000 and 2002 (P ‫؍‬ .005), and treatment-related mortality declined from 19% to 12% (P ‫؍‬ .025). Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88%, similar to historical controls. Postremission survival was 56% in patients randomized to either 5-drug reinduction or fludarabine/ cytarabine/idarubicin. For patients with or without a related donor, respective 5-year disease-free survival was 61% and 50% (P ‫؍‬ .021); respective survival was 68% and 62% (P ‫؍‬ .425). Donor availability conferred no benefit on those with inv(16) or t(8;21) cytogenetics. After cytarabine intensification, patients randomized to interleukin-2 or none experienced similar outcomes. Factors predictive of inferior survival were age more than 16 years, non-white ethnicity, absence of related donor, obesity, white blood cell count more than 100 000 ؋ 10 9 /L, ؊7/7q؊, ؊5/5q؊, and/or complex karyo- IntroductionIn the past 2 decades, cooperative group trials in pediatric acute myeloid leukemia (AML) have increased overall 5-year survival (OS) from approximately 30% to more than 50%. [1][2][3][4][5][6] Intensification of dose, increased number of days of conventional induction chemotherapy, matched related donor bone marrow transplantation (MRD BMT) in first remission, and risk stratification of treatment have all contributed to this progress. Risk stratification typically classifies as favorable those patients with Down syndrome or with AML characterized by t(8;21), t(15;17), or inv(16) cytogenetic abnormalities and rapid early response to induction therapy. Unfavorable features include high white blood cell count, Ϫ7/7qϪ, Ϫ5/5qϪ, or complex cytogenetics, and slow or no early response. [7][8][9][10][11] The emerging consensus is that patients with favorable AML do not benefit from MRD BMT in first remission. 2,12 Since 1986, the Children's Cancer Group (CCG) explored a strategy to treat newly diagnosed AML using intensively timed 5-drug combination chemotherapy consisting of dexamethasone, cytarabine, thioguanine, etoposide, and rubidomycin (daunomycin) (DCTER) for remission induction followed by BMT for patients with matched related donors or intensively timed high-dose cytarabine/asparaginase (HidAC) after remission therapy for patients without related donors. [13][14][15] Intensive timing involves administration of the second cycle of 5 drugs on day 10 regardless of remission status or blood counts. In the previous phase 3 trial, CCG-2891, intensively timed DCTER achieved an event-free survival (EFS) of 41% and OS of 49% at 5 years.This manuscript describes the successor phase...

The primary objective was to describe the prevalence and characteristics of microbiologically defined infections and infection-related mortality (IRM)

BACKGROUND:The development of antigen-targeted therapies may provide additional options to improve outcomes in children with acute myeloid leukemia (AML). The Children's Oncology Group AAML03P1 trial sought to determine the safety of adding 2 doses of gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted agent, to intensive chemotherapy during remission induction and postremission intensification for children with de novo AML. METHODS: AAML03P1 enrolled 350 children with previously untreated AML. Patients with a matched family donor received 3 courses of chemotherapy followed by hematopoietic stem cell transplantation; those without a matched family donor received 5 courses of chemotherapy. Gemtuzumab ozogamicin 3 mg/m 2 /dose was administered on Day 6 of Course 1 and Day 7 of Course 4. RESULTS: Toxicities observed in all courses of therapy were typical of AML chemotherapy regimens, with infection being most common. Patients achieved a complete remission rate of 83% after 1 course and 87% after 2 courses. The mortality rate was 1.5% after the first gemtuzumab ozogamicin-containing induction course and 2.6% after 2 induction courses. The 3-year event-free survival and overall survival rates were 53 AE 6% and 66 AE 5%, respectively. CONCLUSIONS: This trial determined that it is safe and feasible to include gemtuzumab ozogamicin in combination with intensive chemotherapy. The survival rates compare favorably with the recently published results of clinical trials worldwide. Cancer 2012;118:761-