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

Eckardt JN, Stoelzel F, Kunadt D, Roellig C, Stasik S, Wagenfuehr L, Joehrens K, Kuithan F, Kraemer A, Scholl S, Hochhaus A, Crysandt M, Brummendorf TH, Naumann R, Steffen B, Kunzmann V, Einsele H, Schaich M, Burchert A, Neubauer A, Schaefer-Eckart K, Schliemann C, Krause S, Herbst R, Haenel M, Hanoun M, Kaiser U, Kaufmann M, Racil Z, Mayer J, Kroschinsky F, Berdel WE, Ehninger G, Serve H, Mueller-Tidow C, Platzbecker U, Baldus CD, Schetelig J, Bornhauser M, Thiede C, Middeke JM (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 15

Journal Issue: 1

DOI: 10.1186/s13045-022-01267-7

Abstract

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) St. Marien-Krankenhaus Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Rems-Murr-Kliniken Germany (DE) Philipps-Universität Marburg Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg Germany (DE) Universitätsklinikum Münster Germany (DE) Klinikum Chemnitz Germany (DE) Universitätsklinikum Essen Germany (DE) St. Bernward Krankenhaus Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Masaryk University Czech Republic (CZ) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE)

How to cite

APA:

Eckardt, J.-N., Stoelzel, F., Kunadt, D., Roellig, C., Stasik, S., Wagenfuehr, L.,... Middeke, J.M. (2022). Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations. Journal of Hematology & Oncology, 15(1). https://doi.org/10.1186/s13045-022-01267-7

MLA:

Eckardt, Jan-Niklas, et al. "Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations." Journal of Hematology & Oncology 15.1 (2022).

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