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

J 2022

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

ECKARDT, J. N., F. STOLZEL, D. KUNADT, C. ROLLIG, S. STASIK et. al.

Basic information

Original name

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

Authors

ECKARDT, J. N. (guarantor), F. STOLZEL, D. KUNADT, C. ROLLIG, S. STASIK, L. WAGENFUHR, K. JOHRENS, F. KUITHAN, A. KRAMER, S. SCHOLL, A. HOCHHAUS, M. CRYSANDT, T. H. BRUMMENDORF, R. NAUMANN, B. STEFFEN, V. KUNZMANN, H. EINSELE, M. SCHAICH, A. BURCHERT, A. NEUBAUER, K. SCHAFER ECKART, C. SCHLIEMANN, S. W. KRAUSE, R. HERBST, M. HANEL, M. HANOUN, U. KAISER, M. KAUFMANN, Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), F. KROSCHINSKY, W. E. BERDEL, G. EHNINGER, H. SERVE, C. MULLER TIDOW, U. PLATZBECKER, C. D. BALDUS, J. SCHETELIG, M. BORNHAUSER, C. THIEDE and J. M. MIDDEKE

Edition

JOURNAL OF HEMATOLOGY & ONCOLOGY, LONDON, BMC, 2022, 1756-8722

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 28.500

RIV identification code

RIV/00216224:14110/22:00126253

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1186/s13045-022-01267-7

UT WoS

000795132900001

Keywords in English

Acute myeloid leukemia; Extramedullary; Leukemia cutis; Chloroma; Myeloid sarcoma

Abstract

V originále

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.

Citovat

ECKARDT, J. N., F. STOLZEL, D. KUNADT, C. ROLLIG, S. STASIK, L. WAGENFUHR, K. JOHRENS, F. KUITHAN, A. KRAMER, S. SCHOLL, A. HOCHHAUS, M. CRYSANDT, T. H. BRUMMENDORF, R. NAUMANN, B. STEFFEN, V. KUNZMANN, H. EINSELE, M. SCHAICH, A. BURCHERT, A. NEUBAUER, K. SCHAFER ECKART, C. SCHLIEMANN, S. W. KRAUSE, R. HERBST, M. HANEL, M. HANOUN, U. KAISER, M. KAUFMANN, Zdeněk RÁČIL, Jiří MAYER, F. KROSCHINSKY, W. E. BERDEL, G. EHNINGER, H. SERVE, C. MULLER TIDOW, U. PLATZBECKER, C. D. BALDUS, J. SCHETELIG, M. BORNHAUSER, C. THIEDE and J. M. MIDDEKE. Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations. JOURNAL OF HEMATOLOGY & ONCOLOGY. LONDON: BMC, 2022, vol. 15, No 1, p. 1-13. ISSN 1756-8722. Available from: https://dx.doi.org/10.1186/s13045-022-01267-7.

@article{1874625,
   author = {Eckardt, J. N. and Stolzel, F. and Kunadt, D. and Rollig, C. and Stasik, S. and Wagenfuhr, L. and Johrens, K. and Kuithan, F. and Kramer, A. and Scholl, S. and Hochhaus, A. and Crysandt, M. and Brummendorf, T. H. and Naumann, R. and Steffen, B. and Kunzmann, V. and Einsele, H. and Schaich, M. and Burchert, A. and Neubauer, A. and Schafer Eckart, K. and Schliemann, C. and Krause, S. W. and Herbst, R. and Hanel, M. and Hanoun, M. and Kaiser, U. and Kaufmann, M. and Ráčil, Zdeněk and Mayer, Jiří and Kroschinsky, F. and Berdel, W. E. and Ehninger, G. and Serve, H. and Muller Tidow, C. and Platzbecker, U. and Baldus, C. D. and Schetelig, J. and Bornhauser, M. and Thiede, C. and Middeke, J. M.},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13045-022-01267-7},
   keywords = {Acute myeloid leukemia; Extramedullary; Leukemia cutis; Chloroma; Myeloid sarcoma},
   language = {eng},
   issn = {1756-8722},
   journal = {JOURNAL OF HEMATOLOGY & ONCOLOGY},
   title = {Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations},
   url = {https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01267-7},
   volume = {15},
   year = {2022}
}

TY  - JOUR
ID  - 1874625
AU  - 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.
PY  - 2022
TI  - Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations
JF  - JOURNAL OF HEMATOLOGY & ONCOLOGY
VL  - 15
IS  - 1
SP  - 1-13
EP  - 1-13
PB  - BMC
SN  - 17568722
KW  - Acute myeloid leukemia
KW  - Extramedullary
KW  - Leukemia cutis
KW  - Chloroma
KW  - Myeloid sarcoma
UR  - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01267-7
N2  - 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.
ER  -

ECKARDT, J. N., F. STOLZEL, D. KUNADT, C. ROLLIG, S. STASIK, L. WAGENFUHR, K. JOHRENS, F. KUITHAN, A. KRAMER, S. SCHOLL, A. HOCHHAUS, M. CRYSANDT, T. H. BRUMMENDORF, R. NAUMANN, B. STEFFEN, V. KUNZMANN, H. EINSELE, M. SCHAICH, A. BURCHERT, A. NEUBAUER, K. SCHAFER ECKART, C. SCHLIEMANN, S. W. KRAUSE, R. HERBST, M. HANEL, M. HANOUN, U. KAISER, M. KAUFMANN, Zdeněk RÁČIL, Jiří MAYER, F. KROSCHINSKY, W. E. BERDEL, G. EHNINGER, H. SERVE, C. MULLER TIDOW, U. PLATZBECKER, C. D. BALDUS, J. SCHETELIG, M. BORNHAUSER, C. THIEDE and J. M. MIDDEKE. Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations. \textit{JOURNAL OF HEMATOLOGY \&{} ONCOLOGY}. LONDON: BMC, 2022, vol.~15, No~1, p.~1-13. ISSN~1756-8722. Available from: https://dx.doi.org/10.1186/s13045-022-01267-7.

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