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Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations

JN. Eckardt, F. Stölzel, D. Kunadt, C. Röllig, S. Stasik, L. Wagenführ, K. Jöhrens, F. Kuithan, A. Krämer, S. Scholl, A. Hochhaus, M. Crysandt, TH. Brümmendorf, R. Naumann, B. Steffen, V. Kunzmann, H. Einsele, M. Schaich, A. Burchert, A....

. 2022 ; 15 (1) : 60. [pub] 20220513

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22018414

BACKGROUND: Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed. METHODS: We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM. RESULTS: AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p < 0.001), FLT3-ITD (OR: 1.72, p < 0.001) and PTPN11 (OR: 2.46, p < 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p < 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p < 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively). CONCLUSION: Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.

Department of Hematology Oncology and Immunology Philipps University Marburg Marburg Germany

Department of Hematology Oncology and Palliative Care Rems Murr Hospital Winnenden Winnenden Germany

Department of Hematology Oncology and Palliative Care Robert Bosch Hospital Stuttgart Germany

Department of Hematology Oncology Hemostaseology and Cell Therapy University Hospital RWTH Aachen Aachen Germany

Department of Hematology University Hospital Essen Essen Germany

Department of Internal Medicine 1 University Hospital Carl Gustav Carus Fetscherstraße 74 01307 Dresden Saxony Germany

Department of Internal Medicine 2 Jena University Hospital Jena Germany

Department of Internal Medicine 5 Paracelsus Medizinische Privatuniversität and University Hospital Nuremberg Nuremberg Germany

Department of Internal Medicine Hematology and Oncology Masaryk University Hospital Brno Czech Republic

Department of Internal Medicine University Hospital Kiel Kiel Germany

Department of Medicine A University Hospital Münster Münster Germany

Department of Pathology University Hospital Carl Gustav Carus Dresden Germany

DKMS Clinical Trials Unit Dresden Germany

German Cancer Research Center and Medical Clinic 5 University Hospital Heidelberg Heidelberg Germany

German Consortium for Translational Cancer Research DKFZ Heidelberg Germany

Medical Care Center University Hospital Carl Gustav Carus Dresden Germany

Medical Clinic 1 Hematology and Celltherapy University Hospital Leipzig Leipzig Germany

Medical Clinic 2 St Bernward Hospital Hildesheim Germany

Medical Clinic 2 University Hospital Frankfurt Frankfurt Germany

Medical Clinic 3 Chemnitz Hospital AG Chemnitz Germany

Medical Clinic 3 St Marien Hospital Siegen Siegen Germany

Medical Clinic 5 University Hospital Erlangen Erlangen Germany

Medical Clinic and Policlinic 2 University Hospital Würzburg Würzburg Germany

National Center for Tumor Diseases Dresden Germany

Citace poskytuje Crossref.org

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