Publication details

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

Authors	ECKARDT J. N. STOLZEL F. KUNADT D. ROLLIG C. STASIK S. WAGENFUHR L. JOHRENS K. KUITHAN F. KRAMER A. SCHOLL S. HOCHHAUS A. CRYSANDT M. BRUMMENDORF T. H. NAUMANN R. STEFFEN B. KUNZMANN V. EINSELE H. SCHAICH M. BURCHERT A. NEUBAUER A. SCHAFER ECKART K. SCHLIEMANN C. KRAUSE S. W. HERBST R. HANEL M. HANOUN M. KAISER U. KAUFMANN M. RÁČIL Zdeněk MAYER Jiří KROSCHINSKY F. BERDEL W. E. EHNINGER G. SERVE H. MULLER TIDOW C. PLATZBECKER U. BALDUS C. D. SCHETELIG J. BORNHAUSER M. THIEDE C. MIDDEKE J. M.
Year of publication	2022
Type	Article in Periodical
Magazine / Source	JOURNAL OF HEMATOLOGY & ONCOLOGY
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01267-7
Doi	http://dx.doi.org/10.1186/s13045-022-01267-7
Keywords	Acute myeloid leukemia; Extramedullary; Leukemia cutis; Chloroma; Myeloid sarcoma
Description	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.