Clinicopathologic and Molecular Analysis of Normal Karyotype Therapy-Related and De Novo Acute Myeloid Leukemia: A Multi-Institutional Study by the Bone Marrow Pathology Group

被引:5
作者
Cantu, Miguel D. [1 ]
Kanagal-Shamanna, Rashmi [2 ]
Wang, Sa A. [2 ]
Kadia, Tapan [2 ]
Bueso-Ramos, Carlos E. [2 ]
Patel, Sanjay S. [3 ]
Geyer, Julia T. [3 ]
Tam, Wayne [3 ]
Madanat, Yazan [1 ]
Li, Peng [4 ]
George, Tracy I. [4 ]
Nichols, Meredith M. [5 ]
Rogers, Heesun J. [5 ]
Liu, Yen-Chun [6 ]
Aggarwal, Nidhi [7 ]
Kurzer, Jason H. [8 ]
Maracaja, Danielle L. V. [9 ]
Hsi, Eric D. [9 ]
Zaiem, Feras [10 ]
Babu, Daniel [10 ]
Foucar, Kathryn [10 ]
Laczko, Dorottya [11 ]
Bagg, Adam [11 ]
Orazi, Attilio [12 ]
Arber, Daniel A. [13 ]
Hasserjian, Robert P. [14 ]
Weinberg, Olga K. [1 ,15 ,16 ]
机构
[1] Univ Texas Southwestern Med Ctr, Dallas, TX USA
[2] Univ Texas MD Anderson Canc Ctr, Houston, TX USA
[3] Weill Cornell Med Ctr, New York, NY USA
[4] Univ Utah, Salt Lake City, UT USA
[5] Cleveland Clin, Beachwood, OH USA
[6] St Judes Res Hosp, Baton Rouge, LA USA
[7] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA
[8] Stanford Univ, Med Sch, Palo Alto, CA USA
[9] Wake Forest Baptist Hlth, Winston Salem, NC USA
[10] Univ New Mexico, Albuquerque, NM USA
[11] Hosp Univ Penn, Perelman Sch Med, Philadelphia, PA USA
[12] Texas Tech Univ Hlth Sci Ctr, St Lubbock, TX USA
[13] Univ Chicago, Chicago, IL USA
[14] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA
[15] Univ Texas Southwestern Med Ctr, Dept Pathol, 2230 Inwood Rd,EB03 220G, Dallas, TX 75235 USA
[16] BioCtr, 2230 Inwood Rd,EB03 220G, Dallas, TX 75235 USA
关键词
MYELODYSPLASTIC SYNDROMES; CLONAL HEMATOPOIESIS; GENETIC PATHWAYS; NEOPLASMS; MUTATIONS; ADULTS; RECOMMENDATIONS; DECITABINE; MANAGEMENT; DIAGNOSIS;
D O I
10.1200/PO.22.00400
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSE Therapy-related acute myeloid leukemias (t-AML) are a heterogenous group of aggressive neoplasms that arise following exposure to cytotoxic chemotherapy and/or ionizing radiation. Many therapy-related myeloid neoplasms (t-MN) are associated with distinct chromosomal aberrations and/or TP53 alterations, but little is known about the clinicopathologic and molecular features of normal karyotype t-AML (NK-t-AML) and whether this t-MN subtype is distinctly different from NK de novo AML (NK-dn-AML).METHODS This multi-institutional study by the Bone Marrow Pathology Group retrospectively evaluated clinicopathologic and molecular characteristics of 335 patients with NK-AML, comprising 105 t-AML and 230 dn-AML cases.RESULTS Patients with t-AML compared with dn-AML exhibit significantly shorter overall survival (OS; median months: 17.6 v 44.2; P < .0001) and relapse-free survival (RFS; median months: 9.1 v 19.2; P = .0018). Frequency of NPM1, FLT3, KRAS, and GATA2 mutations were significantly different in NK-t-AML compared with NK-dn-AML (NPM1 35% v 49%; P = .0493; FLT3 23% v 36%; P = 0494; KRAS 12% v 5%; P = .0465; GATA2 9% v 2% P = .0105), while TP53 mutations were rare. Patients with t-AML more often stratified into intermediate or adverse 2017 ELN genetic risk groups. Favorable ELN risk predicted favorable OS (hazard ratio [HR], 0.4056; 95% CI, 0 to 0.866; P = .020) and RFS (HR, 0.355; 95% CI, 0 to 0.746; P = .006). Among all patients with NK-AML, stem-cell transplant and favorable ELN risk both significantly affected RFS, while therapy-relatedness and age had a borderline significant impact on OS (HR, 1.355; 95% CI, 0.975 to 1.882; P = .070).CONCLUSION To our knowledge, this is the largest study to date to comprehensively evaluate NK-t-AML and provides a framework that may inform our understanding of NK-t-AML disease biology and could potentially help guide therapeutic management and improved disease classification in t-MNs that lack cytogenetic aberrations.
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页数:10
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