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INFOTitle
Acute Myeloid Leukemia (AML) Data Dictionary
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INFONameaml_dev
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INFORelease Notes
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INFOParent Data Modelpcdc_dev
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INFOLicense
Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/)
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INFOD4CG Data Modeling Wiki
https://docs.pedscommons.org/
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INFODisease Consortium Information
https://commons.cri.uchicago.edu/pcdc/
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INFODescription
The AML data dictionary is a consensus data schema built by an international group of pediatric acute myeloid leukemia experts and maintained by Data for the Common Good (D4CG) at the University of Chicago in collaboration with the International Acute Myeloid Leukemia Consortium (INTERACT). It is based on the collective requirements of its contributors.
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INFOTotal Variables
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RowTypeVariableNameDataTypeTierVariableDescriptionVariableCodePermissibleValueValueDescriptionValueCodeImplementationNotesMappings
Modeling notes (Will be ignored in processing)
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DDProtocol
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TDSubject Characteristics
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TGOne row per subject per study
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VDHONEST_BROKER_SUBJECT_IDString
To-do
The identifier assigned to the subject by the honest broker. An individual, organization or system acting for, or on behalf of, a covered entity to collect and provide health information to research investigators in such a manner whereby it would not be reasonably possible for the investigators or others to identify the corresponding patients-subjects directly or indirectly. The honest broker cannot be one of the investigators. The information provided to the investigators by the honest broker may incorporate linkage codes to permit information collation and/or subsequent inquiries (i.e., a "re-identification code"), however the information linking this re- identification code to the patient's identity must be retained by the honest broker and subsequent inquiries are conducted through the honest broker.
ncit:C168949_undefined__undefined_
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VDCONSORTIUMEnum
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The consortium under which this data is being contributed to the Pediatric Cancer Data Commons.
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New VD
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PDINTERACTInternational Pediatric Acute Myeloid Leukemia Consortium (INTERACT). A consortium launched in 2021 as a collaboration between acute myeloid leukemia researchers from Children's Oncology Group, European Pediatric Acute Leukemia, Japan Children's Cancer Group, and St. Jude Children's Research Hospital. To date, INTERACT has identified 18 studies from 10 clinical trials research groups that can be contributed to the data commons, and its statisticians are actively working to harmonize clinical data from more than 6,000 individuals who have had pediatric cancer.
ncit:C192762
New PD
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VDDATA_CONTRIBUTOR_IDEnumTo-do
An identifier assigned to a data contributor.
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PDAIEOPItalian Association of Pediatric Hematology and Oncology. A group from Bologna, Italy, comprised mainly of pediatricians, hematologists, oncologists, surgeons, biologists, nurses and psychologists who are devoted to addressing the problems of hematology, oncology and immunology in the child and adolescent.
ncit:C168887
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PDBFM-SGBerlin-Frankfurt-Munster Study Group. A study group formed in 1975 by three individuals, Hansjorg Riehm in Berlin (B), Bernhard Kornhuber in Frankfurt (F) and Gunther Schellong in Munster (M), who initiated the first multicenter BFM trial. The BFM treatment concept was based on an intensive chemotherapeutic approach employing eight different drugs which led to a revolutionary increase in the survival of children and adolescents with acute lymphoblastic leukemia.
ncit:C168888
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PDCOGChildren's Oncology Group. An NCI-supported clinical cooperative group formed by the merger of the four national pediatric cancer research organizations: the Children's Cancer Group, the Intergroup Rhabdomyosarcoma Study Group, the National Wilms Tumor Study Group, and the Pediatric Oncology Group. The primary objective of the organization is to conduct clinical trials of new therapies for childhood and adolescent cancer. COG develops and coordinates clinical trials conducted at the 238 member institutions that include cancer centers of all major universities and teaching hospitals throughout the U.S. and Canada, as well as sites in Europe and Australia. COG members include over 5000 cancer researchers.ncit:C39353
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PDDCOGDutch Childhood Oncology Group. A collaborating partner in Innovative Therapies for Children with Cancer Consortium (ITCC), a European based consortium to promote the clinical evaluation of new anti-cancer compounds in children with cancer.
ncit:C168889
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PDMRCMedical Research Council. A publicly funded organization that is part of United Kingdom Research and Innovation, and is dedicated to improving human health through world-class medical research.
ncit:C168892
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PDNOPHONordic Society of Pediatric Haematology and Oncology. A collaborative group formed in 1984 with members from Denmark, Finland, Iceland, Lithuania, Norway and Sweden and whose goal was to secure that all Nordic children suffering from leukemia would receive optimal therapy wherever they lived.
ncit:C168893
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PDPPLLSGPolish Pediatric Leukemia/Lymphoma Study Group. A collaborative group established in 1974 that had the original goal of implementing unified protocols with standardized diagnostic criteria and therapy regimens for Hodgkin's disease and acute lymphoblastic leukemia. The prospects were widened to include non-Hodgkin's lymphomas and acute myelogenous leukemia in 1983.
ncit:C168894
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PDSJCRHSaint Jude Children's Research Hospital. The Saint Jude Children's Research Hospital received its NCI designation in 1977 and was awarded status as a comprehensive cancer center by NCI in 2008. Research is focused specifically on childhood cancers, acquired and inherited immunodeficiencies and genetic disorders.ncit:C39510
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PDJACLSJapan Association of Childhood Leukemia Study. A study group in Japan investigating childhood leukemia.
ncit:C168890
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PDJPLSGJapanese Pediatric Leukemia/Lymphoma Study Group. A study group in Japan investigating pediatric leukemia and lymphoma.
ncit:C168891
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VDSTUDY_IDEnum
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A sequence of characters used to identify, name, or characterize the study.
ncit:C83082_undefined__undefined_
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PDAML-BFM83/87
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PDAML-BFM87/93
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PDAML-BFM93
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PDAML-BFM98
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PDML-DS-2006
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PDAML-BFM2004 Interim
skos:exactMatch [AML].[v1.3].[Subject Characteristics].[STUDY_ID].[AMLBFM2004 Interim]
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PDAML-BFM2019
skos:exactMatch [AML].[v1.3].[Subject Characteristics].[STUDY_ID].[AMLBFM2019]
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PDAML-BFM2020
skos:exactMatch [AML].[v1.3].[Subject Characteristics].[STUDY_ID].[AMLBFM2020]
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PDAML-BFM98 Interim 2003
skos:exactMatch [AML].[v1.3].[Subject Characteristics].[STUDY_ID].[AMLBFM98 Interim 2003]
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PDAPL
skos:exactMatch [AML].[v1.3].[Subject Characteristics].[STUDY_ID].[APL]
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PDNOPHOAML1993
skos:exactMatch [AML].[v1.3].[Subject Characteristics].[STUDY_ID].[NOPHOAML1993]
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PDAAML03P1A pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: a report from the Children's Oncology Group. 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. (Cooper TM, Franklin J, Gerbing RB, et al. AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: a report from the Children's Oncology Group. Cancer. 2012;118(3):761-769. doi:10.1002/cncr.26190)
ncit:C168936
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PDAAML0531Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia. This randomized phase III trial is studying combination chemotherapy and gemtuzumab to see how well they work compared with combination chemotherapy alone in treating young patients with newly diagnosed acute myeloid leukemia.. (ClinicalTrials.gov Identifier: NCT00372593)
ncit:C168937
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PDAAML1031A Phase III Randomized Trial for Patients With De Novo AML Using Bortezomib and Sorafenib for Patients With High Allelic Ratio FLT3/ITD. This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia. (ClinicalTrials.gov Identifier: NCT01371981)
ncit:C168938
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PDAML-BFM2004Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. AML induction with liposomal daunorubicin (80 mg/m2 per day for 3 days) shows antileukemic activity comparable to idarubicin (12 mg/m2 per day for 3 days). Liposomal daunorubicin promises to be more active in the t(8;21) subgroup and causes less treatment-related toxicity. (Creutzig U, Zimmermann M, Bourquin JP, et al. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122(1):37-43. doi:10.1182/blood-2013-02-484097)
ncit:C168939
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PDAML-BFM2012Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. The first-line treatment was intensified stepwise from 1987 to 2012 with increased cumulative doses of cytarabine (maximum 47 g/m2 in AML-BFM 98) and anthracycline (maximum 510 mg/m2 in AML-BFM 04; Fig. 1a). The 5-year pOS of 1940 patients registered in the AML-BFM studies showed a continuous, and significant improvement from 1987–1992 (49 ± 3%) to 2011–2012 (76 ± 4%; p < 0.0001) (Rasche M, Zimmermann M, Borschel L, et al. Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia. 2018;32(10):2167-2177. doi:10.1038/s41375-018-0071-7)
ncit:C173250
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PDAML-BFM-Registry2012Impact of a Risk-Adapted Treatment Approach in Pediatric AML: A Report of the AML-BFM Registry 2012. A risk-adapted approach incorporating genetic data, complemented by response evaluation may help to identify patients with high-risk disease (HR) who could benefit from hematopoietic stem cell transplantation (HSCT) at initial disease. From 2012 until 2017 a total of 324 children <18 years of the AML-BFM registry 2012 (hereafter named R12; Germany, Austria and Czech Republic) with de novo AML were included. Chemotherapy followed the best arm of study AML-BFM 2004, but patients were stratified according to new genetic and response-adapted (≥10% leukemic blasts after induction 1 or ≥5% after induction 2) risk criteria with the indication of HSCT in HR patients. (https://doi.org/10.1182/blood-2019-130969)
ncit:C173251
skos:exactMatch [AML].[v1.0].[Subject Characteristics].[STUDY_ID].[AMLBFMRegistry2012]
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PDAML-BFMRegistry2017Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group. This study evaluated response, survival and prognostic factors after a second relapse of AML. Among 1222 pediatric patients of the population-based AML-Berlin–Frankfurt–Munster (BFM) study group (2004 until 2017), 73 patients met the quality parameters for inclusion in this study. Central review of source documentation warranted the accuracy of reported data. (https://doi.org/10.3390/cancers13040789)
ncit:C182031
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PDAML-BFM1998Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. The trial retrospectively analyzed outcome and clinical data of 1940 pediatric AML patients (younger than 18 years of age), enrolled in the population-based AML-BFM trials between 1987 and 2012. (Rasche, M., Zimmermann, M., Borschel, L. et al. Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia 32, 2167–2177 (2018). https://doi.org/10.1038/s41375-018-0071-7)
ncit:C182032
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PDSJCRHAML02A Collaborative Trial for the Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia. The purpose of this randomized study is to compare the effectiveness of two multi-agent chemotherapy regimens using different dosages of cytarabine to eliminate all detectable leukemia. (ClinicalTrials.gov Identifier: NCT00136084)
ncit:C168940
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PDJPLSGAML05Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05: A Multi-Center Phase II Study in Children with Newly Diagnosed Acute Myeloid Leukemia. The purpose of this study is to evaluate an efficacy and safety of the treatment strategy according to the risk stratification based on leukemia cell biology and response to the initial induction therapy in children less than 18 years old with newly diagnosed acute myeloid leukemia (AML), excluding acute promyelocytic leukemia (APL), AML with Down syndrome, secondary AML, AML derived from MDS, AML with multilineage dysplasia, NK/myeloid leukemia, and granulocytic sarcoma. (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000619)
ncit:C168941
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PDAEIOPAML2002Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia. The study evaluated the outcome of 482 children with acute myeloid leukemia (AML) enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 trial. Treatment was stratified according to risk group; hematopoietic stem cell transplantation (HSCT) was used in high-risk (HR) children. (Pession A, Masetti R, Rizzari C, et al. Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia. Blood. 2013;122(2):170-178. doi:10.1182/blood-2013-03-491621)
ncit:C168942
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PDJACLSAML99Outcome in 146 patients with paediatric acute myeloid leukaemia treated according to the AML99 protocol in the period 2003–06 from the Japan Association of Childhood Leukaemia Study. The acute myeloid leukaemia (AML) 99 trial conducted previously in Japan for the treatment of de novo paediatric AML showed excellent results, with a 5-year overall survival (OS) and event-free survival (EFS) of 75·6% and 61·6%, respectively. To examine reproducibility of these results in another cohort, the outcome of 146 newly diagnosed AML paediatric patients prospectively registered in the Japan Association of Childhood Leukaemia Study (JACLS) from 2003 to 2006 was compared to that of 240 patients in the original AML 99 clinical trial. (https://doi.org/10.1111/bjh.12030)
ncit:C168943
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PDDBAML01Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01. Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01. In this multicenter Dutch–Belgian protocol (DB AML-01), 112 children with de novo AML were included. Treatment was stratified according to day 15 bone marrow response after the first induction course. Poor responders received a second course without delay while good responders awaited hematological recovery. Patients achieving CR after two induction courses continued with three consolidation courses without HSCT in CR1. (https://doi.org/10.1002/pbc.27605)
ncit:C168944
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PDMRCAML12Results of a randomized trial in children with Acute Myeloid Leukaemia: Medical Research Council AML12 trial. The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. The first objective of AML12 was to compare the efficacy and toxicity of mitoxantrone with daunorubicin, both given in combination with cytosine and etoposide (MAE versus ADE). The second objective addressed the number of courses. (Gibson BE, Webb DK, Howman AJ, et al. Results of a randomized trial in children with Acute Myeloid Leukaemia: medical research council AML12 trial. Br J Haematol. 2011;155(3):366-376. doi:10.1111/j.1365-2141.2011.08851.x)
ncit:C168945
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PDMRCAML15Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial. Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. This study established that it is feasible to combine GO with conventional chemotherapy. (Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011;29(4):369-377. doi:10.1200/JCO.2010.31.4310)
ncit:C173252
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PDNOPHOAML2004Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004. The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m(2) and repeated after 3 weeks. The study randomized 120 patients; 59 to receive GO. Survival was analyzed on an intention-to-treat basis. A phase 1 trial performed by the Children's Oncology Group (COG) started at a dose of 9 mg/m2 but was reduced to 6 mg/m2 because of liver toxicity. A phase 2 study with GO administered to relapsed AML as 2 doses of 7.5 mg/m2 with a 14-day interval was well tolerated with response rates of 30%-40%. (Hasle H, Abrahamsson J, Forestier E, et al. Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004. Blood. 2012;120(5):978-984. doi:10.1182/blood-2012-03-416701)
ncit:C168946
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PDNOPHOAML2012NOPHO-DBH AML 2012 Protocol. Research Study for Treatment of Children and Adolescents With Acute Myeloid Leukaemia 0-18 Years. This study evaluates the effect of different induction courses in children and adolescents with newly diagnosed acute myeloid leukemia. In the first course patients are randomized to receive either standard anthracycline therapy with mitoxantrone or experimental DaunoXome. (ClinicalTrials.gov Identifier: NCT01828489)
ncit:C173253
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PDPPLLSGAML98Advances in the First Line Treatment of Pediatric Acute Myeloid Leukemia in the Polish Pediatric Leukemia and Lymphoma Study Group from 1983 to 2019. This trial is part of the five consecutive treatment protocols for pediatric acute myeloid leukemia (AML) used in Poland from 1983 to 2019 (excluding promyelocytic, secondary, biphenotypic, and Down syndrome AML). The AML-PPGLBC 98 study included 151/899 children suffering from AML. The use of standardized therapeutic protocols with the successive consideration of genetic prognostic factors and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years. (Czogała M, Balwierz W, Pawińska-Wąsikowska K, et al. Advances in the First Line Treatment of Pediatric Acute Myeloid Leukemia in the Polish Pediatric Leukemia and Lymphoma Study Group from 1983 to 2019. Cancers (Basel). 2021;13(18):4536. Published 2021 Sep 9. doi:10.3390/cancers13184536)
ncit:C173254
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PDAIEOPLAM92Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols. Since 1982, four consecutive studies on childhood acut myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P ¼ 0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy (Pession, Andrea & Rondelli, Roberto & Basso, Giuseppe & Rizzari, C & Testi, Anna Maria & Fagioli, Franca & Stefano, Piero & Locatelli, Franco. (2005). Treatment and long term results in children with acute myeloid leukemia treated according to the AIEOP AML protocols. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 19. 2043-53. 10.1038/sj.leu.2403869)
ncit:C173255
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PDSCFEELAM02Maintenance Therapy With Interleukin-2 for Childhood AML: Results of ELAM02 Phase III Randomized Trial. This study looks into whether maintenance therapy with interleukin-2 (IL2), for 1 year, improves disease-free survival (DFS) since relapse remains the commonest cause of death (Petit A, Ducassou S, Leblanc T, et al. Maintenance Therapy With Interleukin-2 for Childhood AML: Results of ELAM02 Phase III Randomized Trial. Hemasphere. 2018;2(6):e159. Published 2018 Nov 29. doi:10.1097/HS9.0000000000000159)
ncit:C168947
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VDAGE_AT_ENROLLMENTInteger
To-do
The age (in days) when the subject enrolled in the study.
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ConditionalStatement: if 'ENROLLED_STATUS' == 'Enrolled' | ConditionalStatement: Mandatory if "AGE_AT_DIAG_ASSESSMENT" is null
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VDTREATMENT_ARMEnum
To-do
A specific treatment plan within a clinical trial that describes the activities a subject will be involved in as he or she progresses through the study.
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PDAAML1031:Arm A HRPatients randomized with the following course sequence for high risk (HR) group: 1) Induction I: Patients receive cytarabine intrathecally (IT) on day 1 and ADE chemotherapy comprising cytarabine intravenously (IV) over 1-30 minutes on days 1-10; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5; and etoposide IV over 1-2 hours on days 1-5, 2) Induction II: Patients with low risk (LR) receive cytarabine IT and ADE chemotherapy as in Induction I. Patients with high risk (HR) receive cytarabine IT on day 1 and MA chemotherapy comprising high-dose cytarabine IV over 1-3 hours on days 1-4, and mitoxantrone IV over 15-30 minutes on days 3-6. Patients who achieve complete remission (CR) proceed to Intensification I (beginning on day 37). Patients with refractory disease are off protocol therapy, 3) Intensification I: Patients receive cytarabine IT on day 1 and AE chemotherapy comprising high-dose cytarabine IV over 1-3 hours, and etoposide IV over 1-2 hours on days 1-5. Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. Patients with refractory disease are off protocol therapy, 4) Intensification II: Patients with LR receive cytarabine IT on day 1 and MA chemotherapy as in Induction II. Patients with HR and no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9, 5) Stem Cell Transplantation (SCT): high risk patients with matched family [MFD] or unrelated donor; Conditioning Regimen: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2; Transplantation: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan; GVHD Prophylaxis: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.New PD
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PDAAML1031:Arm A LRPatients randomized with the following course sequence for low risk (LR) group: 1) Induction I: Patients receive cytarabine intrathecally (IT) on day 1 and ADE chemotherapy comprising cytarabine intravenously (IV) over 1-30 minutes on days 1-10; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5; and etoposide IV over 1-2 hours on days 1-5, 2) Induction II: Patients with low risk (LR) receive cytarabine IT and ADE chemotherapy as in Induction I. Patients with high risk (HR) receive cytarabine IT on day 1 and MA chemotherapy comprising high-dose cytarabine IV over 1-3 hours on days 1-4, and mitoxantrone IV over 15-30 minutes on days 3-6. Patients who achieve complete remission (CR) proceed to Intensification I (beginning on day 37). Patients with refractory disease are off protocol therapy, 3) Intensification I: Patients receive cytarabine IT on day 1 and AE chemotherapy comprising high-dose cytarabine IV over 1-3 hours, and etoposide IV over 1-2 hours on days 1-5. Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. Patients with refractory disease are off protocol therapy, 4) Intensification II: Patients with LR receive cytarabine IT on day 1 and MA chemotherapy as in Induction II. Patients with HR and no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.New PD
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PDAAML1031:Arm B HRPatients randomized with the following course sequence gor high risk (HR) group: 1) Induction I: Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, and 8, 2) Induction II: Patients with LR receive cytarabine IT, ADE chemotherapy, and bortezomib as in Induction I. Patients with HR receive cytarabine IT and MA chemotherapy as in Induction II, Arm A (HR patients) and bortezomib IV on days 1, 4, and 8, 3) Intensification I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and bortezomib IV on days 1, 4, and 8. Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. Patients with refractory disease are off protocol therapy, 4) Intensification II: Patients with LR receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), and bortezomib IV on days 1, 4, and 8. Patients with HR and no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9, 5) Stem Cell Transplantation (SCT): high risk (HR) patients with matched family [MFD] or unrelated donor); Conditioning Regimen: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2; Transplatation: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan; GVHD Prophylaxis: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1.New PD
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PDAAML1031:Arm B LRPatients randomized with the following course sequence for low risk (LR) group: 1) Induction I: Patients receive cytarabine IT and ADE chemotherapy as in Induction I, Arm A. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, and 8, 2) Induction II: Patients with LR receive cytarabine IT, ADE chemotherapy, and bortezomib as in Induction I. Patients with HR receive cytarabine IT and MA chemotherapy as in Induction II, Arm A (HR patients) and bortezomib IV on days 1, 4, and 8, 3) Intensification I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and bortezomib IV on days 1, 4, and 8. Patients who achieve CR proceed to Intensification II or stem cell transplantation (SCT) beginning on day 34. Patients with refractory disease are off protocol therapy, 4) Intensification II: Patients with LR receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (HR patients), and bortezomib IV on days 1, 4, and 8. Patients with HR and no donor for SCT receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly (IM) on days 2 and 9.New PD
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PDAAML1031:Arm CPatients randomized with the following course sequence: 1) In Cohort 1 HR: Induction I: Patients receive cytarabine IT on day 1, cytarabine IV over 1-30 minutes on days 1-8, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 3, and 5, etoposide IV over 1-2 hours on days 1-5, and sorafenib tosylate PO on days 9-36; In Cohort 2 HR: Induction I: Patients receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I and sorafenib tosylate PO at the time of known HR FLT3/ITD+ (including in Induction I and concurrently with chemotherapy); In Cohort 3 HR: Induction I: Patients receive cytarabine IT and ADE chemotherapy as in Arm A, Induction I and sorafenib tosylate PO on days 11-28, 2) Intensification I: Patients receive cytarabine IT and AE chemotherapy in Arm A, Intensification II, and sorafenib tosylate PO on daily on days 6-28, 3) Intensification II: Patients receive cytarabine IT on day 1, MA chemotherapy as in Arm A, Induction II (high risk patients), and sorafenib tosylate PO on days 7-34, 4) Stem Cell Transplantation (SCT): high risk (HR) patients with matched family [MFD] or unrelated donor); Conditioning Regimen: Patients receive fludarabine phosphate IV over 30 minutes once daily on days -5 to -2 and busulfan IV over 2 hours 4 times daily on days -5 to -2; Transplantation: Patients undergo allogeneic SCT within 36 to 48 hours after the last dose of busulfan; GVHD Prophylaxis: Patients receive tacrolimus IV continuously or PO beginning on day -2 and continuing until day 98 (matched sibling donor) or day 180 (with taper) (other related/unrelated donors or cord blood) and methotrexate IV on days 1, 3, and 6 (matched sibling/cord blood donors) or days 1, 3, 6, and 11 (other related/unrelated donors). Patients with unrelated donors also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1; Maintenance: Patients receive sorafenib tosylate PO starting on day 40-100 after completion of intensification II or SCT for one year.New PD
69
PD
AEIOP LAM 2002:ICE-ICE-AVE-HAM- HD-AraC/SR
Patients received treatment in the following course sequence for standard risk (SR) group: 1) Remission Induction: Idarubicin given with etoposide and cytarabine (ICE), 2) Remission Induction: Idarubicin given with etoposide and cytarabine (ICE), 3) Etoposide given with cytarabine (AVE), 4) Consolidation 2: Cytarabine given with mitoxantrone (HAM), 5) Cytarabine (HD Ara-C, for standard risk patients only) .New PD
70
PD
AEIOP LAM 2002:ICE-ICE-AVE-HAM-SCT/HR
Patients received treatment in the following course sequence for high risk (HR) group: 1) Remission Induction: Idarubicin given with etoposide and cytarabine (ICE), 2) Remission Induction: Idarubicin given with etoposide and cytarabine (ICE), 3) Etoposide given with cytarabine (AVE), 4) Consolidation 2: Cytarabine given with mitoxantrone (HAM), 5) Auto/Allo SCT (for high risk patients only).New PD
71
PDAAML0531:HRPatients are stratified according to relapse risk (high vs low). Patients are randomized to one of two treatment arms.New PD
72
PDAAML0531:LRPatients are stratified according to relapse risk (high vs low). Patients are randomized to one of two treatment arms.New PD
73
PDAAML0531:Arm A HRPatients randomized with the following course sequence for high risk (HR) group: 1) Induction 1: Patients receive cytarabine IT at the time of diagnosis or on day 1. Patients also receive cytarabine IV on days 1-10, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, all patients (regardless of remission status) proceed to induction 2, 2) Induction 2: Patients receive cytarabine IT on day 1, cytarabine IV on days 1-8, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, patients in complete remission (CR) proceed to intensification 1. Patients with refractory disease are removed from protocol therapy, 3) Intensification 1: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 1 hour on days 1-5, and etoposide IV over 1 hour on days 1-5. After 3 weeks of rest, patients in remission proceed to intensification 2, followed by intensification 3. Patients in remission proceed to allogeneic SCT 2-8 weeks after blood counts recover. Patients with high-risk disease with an alternative donor proceed to intensification 2 and 3, followed by allogeneic SCT. Patients not in remission are removed from protocol therapy, 4) Intensification 2: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 2 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour on days 3-6. After 3 weeks of rest, patients proceed to intensification 3, 5) Intensification 3: Patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly on days 2 and 9.New PD
74
PDAAML0531:Arm A LRPatients randomized with the following course sequence for low risk (LR) group: 1) Induction 1: Patients receive cytarabine IT at the time of diagnosis or on day 1. Patients also receive cytarabine IV on days 1-10, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, all patients (regardless of remission status) proceed to induction 2, 2) Induction 2: Patients receive cytarabine IT on day 1, cytarabine IV on days 1-8, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, patients in complete remission (CR) proceed to intensification 1. Patients with refractory disease are removed from protocol therapy, 3) Intensification 1: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 1 hour on days 1-5, and etoposide IV over 1 hour on days 1-5. After 3 weeks of rest, patients in remission proceed to intensification 2, followed by intensification 3. Patients in remission proceed to allogeneic SCT 2-8 weeks after blood counts recover. Patients with high-risk disease with an alternative donor proceed to intensification 2 and 3, followed by allogeneic SCT. Patients not in remission are removed from protocol therapy.New PD
75
PDAAML0531:Arm B HRPatients randomized with the following course sequence for high risk (HR) group: 1) Induction 1: Patients receive treatment as in induction 1 of arm I. Patients also receive gemtuzumab ozogamicin (GMTZ) IV over 2 hours on day 6, 2) Induction 2: Patients receive treatment as in induction 2 of arm I, 3) Intensification 1: Patients receive treatment as in intensification 1 of arm I, 4) Intensification 2: Patients receive treatment as in intensification 2 of arm I. Patients also receive GMTZ IV over 2 hours on day 7, 5) Intensification 3: Patients receive treatment as in intensification 3 of arm I, 6) Allogeneic SCT (for patients with intermediate- or high-risk disease); MFD: Patients receive a conditioning regimen comprising busulfan IV over 2 hours every 6 hours on days -9 to -6 and cyclophosphamide IV over 1 hour on days -5 to -2. Patients undergo allogeneic SCT on day 0. Patients receive cyclosporine IV or orally twice daily on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11. Patients receive graft-vs-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1-4 hours or orally twice daily on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11; Matched alternative donor: Patients receive a conditioning regimen comprising busulfan and cyclophosphamide as above. Patients also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1. Patients then undergo allogeneic SCT and receive GVHD prophylaxis as above.New PD
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PDAAML0531:Arm B LRPatients randomized with the following course sequence for low risk (LR) group: 1) Induction 1: Patients receive treatment as in induction 1 of arm I. Patients also receive gemtuzumab ozogamicin (GMTZ) IV over 2 hours on day 6, 2) Induction 2: Patients receive treatment as in induction 2 of arm I, 3) Intensification 1: Patients receive treatment as in intensification 1 of arm I, 4) Intensification 2: Patients receive treatment as in intensification 2 of arm I. Patients also receive GMTZ IV over 2 hours on day 7, 5) Intensification 3: Patients receive treatment as in intensification 3 of arm I.New PD
77
PD
MRC AML12:ADE-ADE-MACE-CLASP-MidAC
Patients randomized with the following course sequence: 1) Daunorubicin given in combination with cytarabine and etoposide (ADE), 2) Daunorubicin given in combination with cytarabine and etoposide (ADE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) High dose (HD) cytosine with asparaginase (CLASP), 5) Mitoxantrone given in combination with cytarabine (MidAC).New PD
78
PD
MRC AML12:ADE-ADE-MACE-CLASP-SCT
Patients randomized with the following course sequence: 1) Daunorubicin given in combination with cytosine and etoposide (ADE), 2) Daunorubicin given in combination with cytosine and etoposide (ADE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) High dose (HD) cytosine with asparaginase (CLASP), 5) Allogeneic Stem Cell Transplantation (Allo-SCT).New PD
79
PDMRC AML12:ADE-ADE-MACE-MidACPatients randomized with the following course sequence: 1) Daunorubicin given in combination with cytosine and etoposide (ADE), 2) Daunorubicin given in combination with cytosine and etoposide (ADE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) Mitoxantrone given in combination with cytarabine (MidAC).New PD
80
PDMRC AML12:ADE-ADE-MACE-SCTPatients randomized with the following course sequence: 1) Daunorubicin given in combination with cytosine and etoposide (ADE), 2) Daunorubicin given in combination with cytosine and etoposide (ADE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) Allogeneic Stem Cell Transplantation (SCT).New PD
81
PDMRC AML12:ADE-ADE-off trialPatients randomized with the following course sequence: 1) Daunorubicin given in combination with cytosine and etoposide (ADE), 2) Daunorubicin given in combination with cytosine and etoposide (ADE), 3) Off trial if patient is not complete remission.New PD
82
PD
MRC AML12:MAE-MAE-MACE-CLASP-MidAC
Patients randomized with the following course sequence: 1) Mitoxantrone given in combination with cytosine and etoposide (MAE), 2) Mitoxantrone given in combination with cytosine and etoposide (MAE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) High dose (HD) cytosine with asparaginase (CLASP), 5) Mitoxantrone given in combination with cytarabine (MidAC).New PD
83
PD
MRC AML12:MAE-MAE-MACE-CLASP-SCT
Patients randomized with the following course sequence: 1) Mitoxantrone given in combination with cytosine and etoposide (MAE), 2) Mitoxantrone given in combination with cytosine and etoposide (MAE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) High dose (HD) cytosine with asparaginase (CLASP), 5) Allogeneic Stem Cell Transplantation (SCT).New PD
84
PDMRC AML12:MAE-MAE-MACE-MidACPatients randomized with the following course sequence: 1) Mitoxantrone given in combination with cytosine and etoposide (MAE), 2) Mitoxantrone given in combination with cytosine and etoposide (MAE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) Mitoxantrone given in combination with cytarabine (MidAC).New PD
85
PDMRC AML12:MAE-MAE-MACE-SCTPatients randomized with the following course sequence: 1) Mitoxantrone given in combination with cytosine and etoposide (MAE), 2) Mitoxantrone given in combination with cytosine and etoposide (MAE), 3) Amsacrine given in combination with cytarabine and etoposide (MACE), 4) Allogeneic Stem Cell Transplantation (SCT).New PD
86
PDMRC AML12:MAE-MAE-Off TrialPatients randomized with the following course sequence: 1) Mitoxantrone, cytosine, etoposide (MAE), 2) Mitoxantrone, cytosine, etoposide (MAE), 3) Amsacrine, cytarabine and etoposide (MACE), 4) Off trial if patient is not complete remission.New PD
87
PD
MRC AML15:ADE-ADE-MACE-MidAC-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE), 4) Mitozantrone, cytosine arabinoside (MidAC), 5) Ara-CNew PD
88
PD
MRC AML15:ADE-ADE-MACE-MidAC-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin 50 mg/m2 d1,3,5; cytarabine 100 mg/m2 d1-10 every 12h; etoposide 100 mg/m2 d1-5 (ADE), 2) Daunorubicin 50 mg/m2 d1,3,5; cytarabine 100 mg/m2 d1-8 every 12h; etoposide 100 mg/m2 d1-5 (ADE), 3) Amsacrine 100 mg/m2 d1-5; cytarabine 200 mg/m2 continuous d1-5; etoposide 100 mg/m2 d1-5 (MACE), 4) Mitozantrone 10 mg/m2 daily by slow IV push on d1-5 inclusive (5 doses), cytosine arabinoside 1.0 mg/m2 12-hourly by 2h IV infusion on d1-3 inclusive (6 doses) (MidAC), 5) No further treatment afterwards.New PD
89
PD
MRC AML15:ADE-ADE-MACE/Mytolarg-MidAC-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE)/Gemtuzumab Ozogamicin, 4) Mitozantrone, cytosine arabinoside (MidAC), 5) Ara-CNew PD
90
PD
MRC AML15:ADE-ADE-MACE/Mytolarg-MidAC-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE)/Gemtuzumab Ozogamicin, 4) Mitozantrone, cytosine arabinoside (MidAC), 5) No further treatment afterwards.New PD
91
PD
MRC AML15:ADE/Mytolarg-ADE-MACE-MidAC-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE)/Gemtuzumab Ozogamicin, 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE), 4) Mitozantrone, cytosine arabinoside (MidAC), 5) Ara-CNew PD
92
PD
MRC AML15:ADE/Mytolarg-ADE-MACE-MidAC-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE)/Gemtuzumab Ozogamicin, 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE), 4) Mitozantrone, cytosine arabinoside (MidAC), 5) No further treatment afterwards.New PD
93
PD
MRC AML15:ADE/Mytolarg-ADE-MACE/Mytolarg-MidAC-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE)/Gemtuzumab Ozogamicin, 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE)/Gemtuzumab Ozogamicin, 4) Mitozantrone, cytosine arabinoside (MidAC), 5) Ara-CNew PD
94
PD
MRC AML15:ADE/Mytolarg-ADE-MACE/Mytolarg-MidAC-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE)/Gemtuzumab Ozogamicin, 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Amsacrine, cytarabine, etoposide (MACE)/Gemtuzumab Ozogamicin, 4) Mitozantrone, cytosine arabinoside (MidAC), 5) No further treatment afterwards.New PD
95
PD
MRC AML15:ADE-ADE-AraC3g-AraC3g-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Ara-C 3.0 g/m2, 4) Ara-C , 5) Ara-C 1.5 g/m2.New PD
96
PD
MRC AML15:ADE-ADE-AraC3g-AraC3g-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Ara-C 3.0 g/m2, 4) Ara-C 3.0 g/m2, 5) No further treatment afterwards.New PD
97
PD
MRC AML15:ADE-ADE-AraC3g/Mytolarg-AraC3g-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Ara-C 3.0 g/m2 (AraC3g)/Gemtuzumab Ozogamicin, 4) Ara-C 3.0 g/m2, 5) Ara-C 1.5 g/m2New PD
98
PD
MRC AML15:ADE-ADE-AraC3g/Mytolarg-AraC3g-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE), 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Ara-C 3.0 g/m2/Gemtuzumab Ozogamicin, 4) Ara-C 3.0 g/m2, 5) No futher treatment afterwards.New PD
99
PD
MRC AML15:ADE/Mytolarg-ADE-AraC3g-AraC3g-AraC
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE)/Gemtuzumab Ozogamicin, 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Ara-C 3.0 g/m2, 4) Ara-C 3.0 g/m2, 5) Ara-C 1.5 g/m2New PD
100
PD
MRC AML15:ADE/Mytolarg-ADE-AraC3g-AraC3g-No Further Therapy
Patients randomized with the following course sequence: 1) Daunorubicin, cytarabine, etoposide (ADE)/Gemtuzumab Ozogamicin, 2) Daunorubicin, cytarabine, etoposide (ADE), 3) Ara-C 3.0 g/m2, 4) Ara-C 3.0 g/m2, 5) No further treatment afterwards.New PD