Institution
Children's Oncology Group
Nonprofit•Geneva, Switzerland•
About: Children's Oncology Group is a nonprofit organization based out in Geneva, Switzerland. It is known for research contribution in the topics: Leukemia & Myeloid leukemia. The organization has 418 authors who have published 763 publications receiving 29731 citations.
Topics: Leukemia, Myeloid leukemia, Cancer, Transplantation, Population
Papers published on a yearly basis
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TL;DR: This study documents ongoing survival improvements for children and adolescents with acute lymphoblastic leukemia, emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure.
Abstract: Purpose To examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children’s Oncology Group (COG) clinical trials between 1990 and 2005.
934 citations
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TL;DR: The addition of MTP to chemotherapy might improve EFS, but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP.
Abstract: Purpose To determine whether the addition of ifosfamide and/or muramyl tripeptide (MTP) encapsulated in liposomes to cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) could improve the probability for event-free survival (EFS) in newly diagnosed patients with osteosarcoma (OS). Patients and Methods Six hundred seventy-seven patients with OS without clinically detectable metastatic disease were treated with one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and HDMTX and underwent definitive surgical resection of the primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 × 2 factorial design. The primary end point for analysis was EFS. Results Patients treated with the standard arm of therapy had a 3-year EFS of 71%. We could not analyze the results by factorial design because we observed an interaction between the addition of ifosfamide and the addition of MTP. The addition ...
615 citations
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TL;DR: The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma, and the addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.
Abstract: Purpose To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma. Patients and Methods Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 × 2 factorial design. The primary end points for analysis were EFS and overall survival. Results In the current analysis, there was no evidence of interaction, and...
615 citations
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TL;DR: The findings suggest that a targeted inhibitor of ALK has antitumour activity in childhood malignancies harbouring ALK translocations, particularly anaplastic large-cell lymphoma and inflammatory myofibroblastic tumours, and that further investigation in the subset of neuroblastoma harbouring known ALK oncogenic mutations is warranted.
Abstract: Summary Background Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. Methods In this open-label, phase 1 dose-escalation trial, patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours, or anaplastic large-cell lymphoma, refractory to therapy and for whom there was no known curative treatment were eligible. Crizotinib was given twice daily without interruption. Six dose levels (100, 130, 165, 215, 280, 365 mg/m 2 per dose) were assessed in the dose-finding phase of the study (part A1), which is now completed. The primary endpoint was to estimate the maximum tolerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of crizotinib in children with refractory cancer. Additionally, patients with confirmed ALK translocations, mutations, or amplification (part A2 of the study) or neuroblastoma (part A3) could enrol at one dose level lower than was currently given in part A1. We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma. All patients who received at least one dose of crizotinib were evaluable for response; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity. This study is registered with ClinicalTrials.gov, NCT00939770. Findings 79 patients were enrolled in the study from Oct 2, 2009, to May 31, 2012. The median age was 10·1 years (range 1·1–21·4); 43 patients were included in the dose escalation phase (A1), 25 patients in part A2, and 11 patients in part A3. Crizotinib was well tolerated with a recommended phase 2 dose of 280 mg/m 2 twice daily. Grade 4 adverse events in cycle 1 were neutropenia (two) and liver enzyme elevation (one). Grade 3 adverse events that occurred in more than one patient in cycle 1 were lymphopenia (two), and neutropenia (eight). The mean steady state peak concentration of crizotinib was 630 ng/mL and the time to reach this peak was 4 h (range 1–6). Objective tumour responses were documented in 14 of 79 patients (nine complete responses, five partial responses); and the anti-tumour activity was enriched in patients with known activating ALK aberrations (eight of nine with anaplastic large-cell lymphoma, one of 11 with neuroblastoma, three of seven with inflammatory myofibroblastic tumour, and one of two with NSCLC). Interpretation The findings suggest that a targeted inhibitor of ALK has antitumour activity in childhood malignancies harbouring ALK translocations, particularly anaplastic large-cell lymphoma and inflammatory myofibroblastic tumours, and that further investigation in the subset of neuroblastoma harbouring known ALK oncogenic mutations is warranted. Funding Pfizer and National Cancer Institute grant to the Children's Oncology Group.
604 citations
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Children's Oncology Group1, University of New Mexico2, St. Jude Children's Research Hospital3, University of Alabama at Birmingham4, University of Georgia5, New York University6, University of Florida7, Medical College of Wisconsin8, Children's National Medical Center9, University of Colorado Denver10
TL;DR: Observations suggest that activation of CRLF2 expression, mutation of JAK kinases, and alterations of IKZF1 cooperate to promote B-cell leukemogenesis and identify these pathways as important therapeutic targets in this disease.
502 citations
Authors
Showing all 418 results
Name | H-index | Papers | Citations |
---|---|---|---|
Leslie L. Robison | 131 | 854 | 64373 |
Xiao-Ou Shu | 121 | 1045 | 63394 |
Susana C. Raimondi | 98 | 413 | 35297 |
Daniel O. Stram | 95 | 445 | 35983 |
Stephen P. Hunger | 91 | 522 | 31453 |
Tamas Revesz | 90 | 374 | 30861 |
Irwin D. Bernstein | 89 | 311 | 26624 |
Cheryl L. Willman | 88 | 301 | 34013 |
Jerald P. Radich | 88 | 412 | 37725 |
Sarah S. Donaldson | 87 | 413 | 26743 |
Mark Krailo | 85 | 394 | 22772 |
Bruce M. Camitta | 83 | 326 | 23700 |
Nyla A. Heerema | 83 | 375 | 27567 |
Robert C. Seeger | 82 | 220 | 23601 |
Mignon L. Loh | 82 | 407 | 35918 |