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.

Základní údaje

Originální název

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

Autoři

ECKARDT, J. N. (garant), 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 Česká republika, domácí), Jiří MAYER (203 Česká republika, domácí), F. KROSCHINSKY, W. E. BERDEL, G. EHNINGER, H. SERVE, C. MULLER TIDOW, U. PLATZBECKER, C. D. BALDUS, J. SCHETELIG, M. BORNHAUSER, C. THIEDE a J. M. MIDDEKE

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 28.500

Kód RIV

RIV/00216224:14110/22:00126253

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000795132900001

Klíčová slova anglicky

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

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 7. 2022 09:00, Mgr. Tereza Miškechová

Anotace

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 a J. M. MIDDEKE. Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations. JOURNAL OF HEMATOLOGY & ONCOLOGY. LONDON: BMC, 2022, roč. 15, č. 1, s. 1-13. ISSN 1756-8722. Dostupné z: 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 a 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, roč.~15, č.~1, s.~1-13. ISSN~1756-8722. Dostupné z: https://dx.doi.org/10.1186/s13045-022-01267-7.

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