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This will be a translational study without any therapeutic intervention, for the purpose of analyzing the diagnostic and molecular results / characterization of adult patients with AML, regardless of the treatment they receive. Newly diagnosed or relapsed/resistant AML patients will be included.
This will be a multicenter, translational study without any therapeutic intervention. It will be conducted at 7 central laboratories (Hospital Universitari i Politècnic La Fe, Hospital Universitario de Salamanca, Hospital 12 de Octubre, Hospital Universitario Virgen del Rocío, Hospital Dr. Negrín de Las Palmas de Gran Canaria, Hospital Reina Sofía de Córdoba and Clínica Universidad de Navarra) belonging to the Spanish PETHEMA Group. The laboratories will receive and process bone marrow and peripheral blood samples of patients with AML at the time of the initial diagnosis or at relapse or resistance (first or subsequent relapse/resistance). The demographic data and clinical characteristics of the patients and of the AML, morphological and molecular response will be collected in case report forms (CRFs). Since the aim of this study is the molecular diagnosis of AML, all patients with AML will be included, regardless of the treatment (or no treatment at all) they receive.
The physicians will receive the report about the molecular diagnosis for FLT3, NPM1, CBF and PML/RARa quickly (<48-96 hours), in order to provide them with knowledge of the mutational status, that may cause changes to be made during the initial management of the disease.
The aim of this project is to set up this rapid screening and diagnostic platform for AML by having specimens sent to 7 centralized reference laboratories across the country, where the molecular characteristics of leukemic cells will be analyzed by qRT-PCR and NGS technologies with high quality standards. This platform will provide homogeneous criteria for assessing the biological characteristics of the different entities that make up the disease.
It is expected that samples of marrow and/or blood of 700 patients with AML will be analyzed per year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute Myeloid Leukemia (AML) | Newly diagnosed or relapsed/resistant AML |
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| Measure | Description | Time Frame |
|---|---|---|
| Frequency of FLT3, NPM1 and CEBPa mutations | Frequency of each of the standard screening panel molecular alterations studied in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease. | Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of mutations detected by Next Generation Sequency (NGS) | Frequency of mutations detected by NGS PCR (23 genes: FLT3, NPM1, DNMT3A, IDH2, IDH1, TET2, RUNX1, TP53, NRAS, WT1, PTPN11, KIT, U2AF1, KRAS, SMC1A, SMC3, PHF6, STAG2, RAD21, FAM5C, EZH2 and HNRNPK; if new genes are described,the panel can be extended) in every sample (diagnosis, relapse) | Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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Patients aged ≥18 years with a diagnosis of AML (new, relapse or refractory).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Olga Garcia | Contact | +34 609 128 678 | publi@fundacionpethema.es |
| Name | Affiliation | Role |
|---|---|---|
| Pau Montesinos | Hospital Universitario La Fe | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Reina Sofía | Recruiting | Córdoba | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19880497 | Background | Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30. | |
| 18987736 |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Bone marrow and peripheral blood samples
| Frequency of mutations detected by conventional PCR (FLT3, NPM1 and CEBPa) in every sample (diagnosis, relapse) | Frequency of each of the standard screening panel molecular alterations studied by the conventional PCR in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease. | Baseline |
| Hospital Universitario de Gran Canaria Dr. Negrín | Recruiting | Las Palmas de Gran Canaria | Spain |
|
| Hospital Doce de Octubre | Recruiting | Madrid | Spain |
|
| Clínica Universidad de Navarra | Recruiting | Pamplona | Spain |
|
| Hospital Universitario de Salamanca | Recruiting | Salamanca | Spain |
|
| Hospital Universitario Virgen del Rocío | Recruiting | Seville | Spain |
|
| Hospital Universitario La Fe | Recruiting | Valencia | Spain |
|
| Background |
| Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. |
| 24106950 | Background | Miller CA, Wilson RK, Ley TJ. Genomic landscapes and clonality of de novo AML. N Engl J Med. 2013 Oct 10;369(15):1473. doi: 10.1056/NEJMc1308782. No abstract available. |
| 19008455 | Background | Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, Tidefelt U, Wahlin A, Hoglund M. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009 Apr 30;113(18):4179-87. doi: 10.1182/blood-2008-07-172007. Epub 2008 Nov 13. |
| 27895058 | Background | Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |