Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements

被引：0

作者：

Bataller, Alex ^{[1
]}

Goulart, Hannah E. ^{[1
]}

Issa, Ghayas C. ^{[1
]}

Dinardo, Courtney D. ^{[1
]}

Daver, Naval ^{[1
]}

Kadia, Tapan ^{[1
]}

Bazinet, Alexandre ^{[1
]}

Bouligny, Ian M. ^{[1
]}

Senapati, Jayastu ^{[1
]}

Haddad, Fadi G. ^{[1
]}

Borthakur, Gautam ^{[1
]}

Sasaki, Koji ^{[1
]}

Short, Nicholas J. ^{[1
]}

Yilmaz, Musa ^{[1
]}

Montalban-Bravo, Guillermo ^{[1
]}

Tang, Guiling ^{[2
]}

Loghavi, Sanam ^{[2
]}

Garcia-Manero, Guillermo ^{[1
]}

Ravandi, Farhad ^{[1
]}

Kantarjian, Hagop ^{[1
]}

Jabbour, Elias ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX USA

来源：

LEUKEMIA | 2025年 / 39卷 / 07期

关键词：

ADULT PATIENTS; BAND; 11Q23; TRANSLOCATIONS; AML; ABNORMALITIES; THERAPY; CANCER;

D O I：

10.1038/s41375-025-02634-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A. Signaling-related genes (NRAS 30%, KRAS 23% and FLT3-TKD 16%) were the most frequently mutated in patients with KMT2Ar AML. Patients treated with intensive chemotherapy (IT) achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 81%, and when combined with venetoclax, the CR/CRi rate increased to 100%. Patients treated with low intensity treatment (LIT) achieved an CR/CRi rate of 33%, and when combined with venetoclax, the CR/CRi rate was 61%. For patients treated with IT, the 5-year overall survival (OS) and event-free survival (EFS) rates were 66% and 64%, respectively, compared with 7% in those treated with LIT. Thirty-nine patients (57%) underwent allogeneic stem cell transplantation after achieving CR/CRi. For patients treated with LIT, multivariate analysis demonstrated that N/KRAS mutations were predictive for OS (HR 2.93, 95% CI 1.18-7.29, P = 0.021) and EFS (HR 3.51, 95% CI 1.35-9.24, P = 0.01). In summary, outcomes in KMT2Ar AML have improved over years in patients treated with IT, whereas those treated with LIT continue to show poor survival, highlighting the need for novel combinations.

引用

页码：1640 / 1649

页数：10

共 29 条

[1] Clinical experience with venetoclax and hypomethylating agents (HMA) in patients with newly diagnosed and relapsed or refractory KMT2A-Rearranged acute myeloid leukemia (AML) [J].

Ball, Brian J. ;

Arslan, Shukaib ;

Koller, Paul ;

Ngo, Dat ;

Afkhami, Michelle ;

Salhotra, Amandeep ;

Al-Malki, Monzr ;

Aribi, Ahmed ;

Ali, Haris ;

Sandhu, Karamjeet ;

Otoukesh, Salman ;

Amanam, Idoroenyi ;

Pourhassan, Hoda ;

Artz, Andrew ;

Curtin, Peter ;

Stein, Anthony ;

Nakamura, Ryotaro ;

Marcucci, Guido ;

Smith, Eileen ;

Pullarkat, Vinod ;

Aldoss, Ibrahim .

LEUKEMIA & LYMPHOMA, 2022, 63 (13) :3232-3236

[2] European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol [J].

Bataller, Alex ;

Garrido, Ana ;

Guijarro, Francesca ;

Onate, Guadalupe ;

Diaz-Beya, Marina ;

Arnan, Montserrat ;

Tormo, Mar ;

Vives, Susana ;

de Llano, Maria Paz Queipo ;

Coll, Rosa ;

Gallardo, David ;

Vall-Llovera, Ferran ;

Escoda, Lourdes ;

Garcia-Guinon, Antonio ;

Salamero, Olga ;

Sampol, Antonia ;

Merchan, Brayan M. ;

Bargay, Joan ;

Castano-Diez, Sandra ;

Esteban, Daniel ;

Oliver-Caldes, Aina ;

Rivero, Andrea ;

Mozas, Pablo ;

Lopez-Guerra, Monica ;

Pratcorona, Marta ;

Zamora, Lurdes ;

Costa, Dolors ;

Rozman, Maria ;

Nomdedeu, Josep F. ;

Colomer, Dolors ;

Brunet, Salut ;

Sierra, Jorge ;

Esteve, Jordi .

BLOOD ADVANCES, 2022, 6 (04) :1193-1206

[3] Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A [J].

Bill, Marius ;

Mrozek, Krzysztof ;

Kohlschmidt, Jessica ;

Eisfeld, Ann-Kathrin ;

Walker, Christopher J. ;

Nicolet, Deedra ;

Papaioannou, Dimitrios ;

Blachly, James S. ;

Orwick, Shelley ;

Carroll, Andrew J. ;

Kolitz, Jonathan E. ;

Powell, Bayard L. ;

Stone, Richard M. ;

de la Chapelle, Albert ;

Byrd, John C. ;

Bloomfield, Clara D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (42) :26340-26346

[4] Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia:: results from Cancer and Leukemia Group B (CALGB 8461) [J].

Byrd, JC ;

Mrózek, K ;

Dodge, RK ;

Carroll, AJ ;

Edwards, CG ;

Arthur, DC ;

Pettenati, MJ ;

Patil, SR ;

Rao, KW ;

Watson, MS ;

Koduru, PRK ;

Moore, JO ;

Stone, RM ;

Mayer, RJ ;

Feldman, EJ ;

Davey, FR ;

Schiffer, CA ;

Larson, RA ;

Bloomfield, CD .

BLOOD, 2002, 100 (13) :4325-4336

[5] Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation [J].

Chen, Y. ;

Kantarjian, H. ;

Pierce, S. ;

Faderl, S. ;

O'Brien, S. ;

Qiao, W. ;

Abruzzo, L. ;

de Lima, M. ;

Kebriaei, P. ;

Jabbour, E. ;

Daver, N. ;

Kadia, T. ;

Estrov, Z. ;

Garcia-Manero, G. ;

Cortes, J. ;

Ravandi, F. .

LEUKEMIA, 2013, 27 (04) :836-842

[6] Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN [J].

Doehner, Hartmut ;

Wei, Andrew H. ;

Appelbaum, Frederick R. ;

Craddock, Charles ;

DiNardo, Courtney D. ;

Dombret, Herve ;

Ebert, Benjamin L. ;

Fenaux, Pierre ;

Godley, Lucy A. ;

Hasserjian, Robert P. ;

Larson, Richard A. ;

Levine, Ross L. ;

Miyazaki, Yasushi ;

Niederwieser, Dietger ;

Ossenkoppele, Gert ;

Roellig, Christoph ;

Sierra, Jorge ;

Stein, Eytan M. ;

Tallman, Martin S. ;

Tien, Hwei-Fang ;

Wang, Jianxiang ;

Wierzbowska, Agnieszka ;

Lowenberg, Bob .

BLOOD, 2022, 140 (12) :1345-1377

[7] Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].

Doehner, Hartmut ;

Estey, Elihu ;

Grimwade, David ;

Amadori, Sergio ;

Appelbaum, Frederick R. ;

Buechner, Thomas ;

Dombret, Herve ;

Ebert, Benjamin L. ;

Fenaux, Pierre ;

Larson, Richard A. ;

Levine, Ross L. ;

Lo-Coco, Francesco ;

Naoe, Tomoki ;

Niederwieser, Dietger ;

Ossenkoppele, Gert J. ;

Sanz, Miguel ;

Sierra, Jorge ;

Tallman, Martin S. ;

Tien, Hwei-Fang ;

Wei, Andrew H. ;

Lowenberg, Bob ;

Bloomfield, Clara D. .

BLOOD, 2017, 129 (04) :424-447

[8] The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial [J].

Grimwade, D ;

Walker, H ;

Oliver, F ;

Wheatley, K ;

Harrison, C ;

Harrison, G ;

Rees, J ;

Hann, I ;

Stevens, R ;

Burnett, A ;

Goldstone, A .

BLOOD, 1998, 92 (07) :2322-2333

[9] Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials [J].

Grimwade, David ;

Hills, Robert K. ;

Moorman, Anthony V. ;

Walker, Helen ;

Chatters, Stephen ;

Goldstone, Anthony H. ;

Wheatley, Keith ;

Harrison, Christine J. ;

Burnett, Alan K. .

BLOOD, 2010, 116 (03) :354-365

[10] Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study [J].

Hernandez-Sanchez, Alberto ;

Gonzalez, Teresa ;

Sobas, Marta ;

Straeng, Eric ;

Castellani, Gastone ;

Abaigar, Maria ;

Valk, Peter J. M. ;

Ramiro, Angela Villaverde ;

Benner, Axel ;

Metzeler, Klaus H. ;

Azibeiro, Raul ;

Tettero, Jesse M. ;

Martinez-Lopez, Joaquin ;

Pratcorona, Marta ;

Elicegui, Javier Martinez ;

Mills, Ken I. ;

Thiede, Christian ;

Sanz, Guillermo ;

Doehner, Konstanze ;

Heuser, Michael ;

Haferlach, Torsten ;

Turki, Amin T. ;

Reinhardt, Dirk ;

Schulze-Rath, Renate ;

Barbus, Martje ;

Hernandez-Rivas, Jesus Maria ;

Huntly, Brian ;

Ossenkoppele, Gert ;

Doehner, Hartmut ;

Bullinger, Lars .

LEUKEMIA, 2024, 38 (09) :1929-1937

← 1 2 3 →