Complex karyotype but not other cytogenetic abnormalities is associated with worse posttransplant survival of patients with nucleophosmin 1-mutated acute myeloid leukemia: A study from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party
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Complex karyotype but not other cytogenetic abnormalities is associated with worse posttransplant survival of patients with nucleophosmin 1-mutated acute myeloid leukemia: A study from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party. / Moukalled, Nour; Labopin, Myriam; Versluis, Jurjen; Socié, Gérard; Blaise, Didier; Salmenniemi, Urpu; Rambaldi, Alessandro; Gedde-Dahl, Tobias; Tholouli, Eleni; Kröger, Nicolaus; Bourhis, Jean-Henri; Von Dem Borne, Peter; Daguindau, Etienne; Forcade, Edouard; Nagler, Arnon; Esteve, Jordi; Ciceri, Fabio; Bazarbachi, Ali; Mohty, Mohamad.
in: AM J HEMATOL, Jahrgang 99, Nr. 3, 03.2024, S. 360-369.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Complex karyotype but not other cytogenetic abnormalities is associated with worse posttransplant survival of patients with nucleophosmin 1-mutated acute myeloid leukemia: A study from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party
AU - Moukalled, Nour
AU - Labopin, Myriam
AU - Versluis, Jurjen
AU - Socié, Gérard
AU - Blaise, Didier
AU - Salmenniemi, Urpu
AU - Rambaldi, Alessandro
AU - Gedde-Dahl, Tobias
AU - Tholouli, Eleni
AU - Kröger, Nicolaus
AU - Bourhis, Jean-Henri
AU - Von Dem Borne, Peter
AU - Daguindau, Etienne
AU - Forcade, Edouard
AU - Nagler, Arnon
AU - Esteve, Jordi
AU - Ciceri, Fabio
AU - Bazarbachi, Ali
AU - Mohty, Mohamad
N1 - © 2024 Wiley Periodicals LLC.
PY - 2024/3
Y1 - 2024/3
N2 - In the 2022 European LeukemiaNet classification, patients with nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (AML) were classified in the adverse-risk category in the presence of high-risk cytogenetics (CG). Nonetheless, the impact of various CG aberrations on posttransplant outcomes remains to be unraveled. This registry study analyzed adult patients with NPM1-mutated de novo AML who underwent their first allogeneic hematopoietic cell transplantation in the first complete remission from 2005 to 2021. A total of 3275 patients were identified, 2782 had normal karyotype, 493 had chromosomal aberrations including 160 with adverse-risk CG, 72 patients had complex karyotype (CK), and 66 monosomal karyotype (MK). Overall, 2377 (73%) patients had FLT3-ITD. On univariate analysis, only FLT3-ITD, minimal/measurable residual disease (MRD) positivity and CK, but not abnormal CG, affected posttransplant outcomes. On multivariable analysis, CK was associated with lower overall survival (OS) (hazard ratio [HR] 1.72, p = .009). In the subgroup of 493 patients with aberrant CG, the 2-year leukemia-free survival (LFS) and OS were around 61% and 68%, respectively. On multivariable analysis for this subgroup, CK and MRD positivity were associated with increased risk of relapse (HR 1.7, p = .025; and 1.99, p = .003 respectively) and worse LFS (HR 1.62, p = .018; and 1.64, p = .011 respectively) while FLT3-ITD, MK, or other CG abnormalities had no significant effect. Importantly, CK negatively affected OS (HR 1.91, p = .002). In the first complete remission transplant setting, CK was found as the only cytogenetic risk factor for worse outcomes in NPM1-mutated AML. Nevertheless, even for this subgroup, a significant proportion of patients can achieve long-term posttransplant survival.
AB - In the 2022 European LeukemiaNet classification, patients with nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (AML) were classified in the adverse-risk category in the presence of high-risk cytogenetics (CG). Nonetheless, the impact of various CG aberrations on posttransplant outcomes remains to be unraveled. This registry study analyzed adult patients with NPM1-mutated de novo AML who underwent their first allogeneic hematopoietic cell transplantation in the first complete remission from 2005 to 2021. A total of 3275 patients were identified, 2782 had normal karyotype, 493 had chromosomal aberrations including 160 with adverse-risk CG, 72 patients had complex karyotype (CK), and 66 monosomal karyotype (MK). Overall, 2377 (73%) patients had FLT3-ITD. On univariate analysis, only FLT3-ITD, minimal/measurable residual disease (MRD) positivity and CK, but not abnormal CG, affected posttransplant outcomes. On multivariable analysis, CK was associated with lower overall survival (OS) (hazard ratio [HR] 1.72, p = .009). In the subgroup of 493 patients with aberrant CG, the 2-year leukemia-free survival (LFS) and OS were around 61% and 68%, respectively. On multivariable analysis for this subgroup, CK and MRD positivity were associated with increased risk of relapse (HR 1.7, p = .025; and 1.99, p = .003 respectively) and worse LFS (HR 1.62, p = .018; and 1.64, p = .011 respectively) while FLT3-ITD, MK, or other CG abnormalities had no significant effect. Importantly, CK negatively affected OS (HR 1.91, p = .002). In the first complete remission transplant setting, CK was found as the only cytogenetic risk factor for worse outcomes in NPM1-mutated AML. Nevertheless, even for this subgroup, a significant proportion of patients can achieve long-term posttransplant survival.
KW - Adult
KW - Humans
KW - Nucleophosmin
KW - Bone Marrow
KW - Mutation
KW - Chromosome Aberrations
KW - Leukemia, Myeloid, Acute/genetics
KW - Hematopoietic Stem Cell Transplantation
KW - Abnormal Karyotype
KW - Karyotype
KW - Neoplasm, Residual
KW - Prognosis
KW - fms-Like Tyrosine Kinase 3/genetics
KW - Retrospective Studies
U2 - 10.1002/ajh.27187
DO - 10.1002/ajh.27187
M3 - SCORING: Journal article
C2 - 38165072
VL - 99
SP - 360
EP - 369
JO - AM J HEMATOL
JF - AM J HEMATOL
SN - 0361-8609
IS - 3
ER -