Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
29
02
2020
accepted:
13
03
2020
revised:
10
03
2020
pubmed:
2
4
2020
medline:
5
1
2021
entrez:
2
4
2020
Statut:
ppublish
Résumé
The revised 2017 European LeukemiaNet (ELN) recommendations for genetic risk stratification of acute myeloid leukemia have been widely adopted, but have not yet been validated in large cohorts of AML patients. We studied 1116 newly diagnosed AML patients (age range, 18-86 years) who had received induction chemotherapy. Among 771 patients not selected by genetics, the ELN-2017 classification re-assigned 26.5% of patients into a more favorable or, more commonly, a more adverse-risk group compared with the ELN-2010 recommendations. Forty percent of the cohort, and 51% of patients ≥60 years, were classified as adverse-risk by ELN-2017. In 599 patients <60 years, estimated 5-year overall survival (OS) was 64% for ELN-2017 favorable, 42% for intermediate-risk and 20% for adverse-risk patients. Among 517 patients aged ≥60 years, corresponding 5-year OS rates were 37, 16, and 6%. Patients with biallelic CEBPA mutations or inv(16) had particularly favorable outcomes, while patients with mutated TP53 and a complex karyotype had especially poor prognosis. DNMT3A mutations associated with inferior OS within each ELN-2017 risk group. Our results validate the prognostic significance of the revised ELN-2017 risk classification in AML patients receiving induction chemotherapy across a broad age range. Further refinement of the ELN-2017 risk classification is possible.
Identifiants
pubmed: 32231256
doi: 10.1038/s41375-020-0806-0
pii: 10.1038/s41375-020-0806-0
pmc: PMC7685975
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3161-3172Références
Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.
pubmed: 19880497
Röllig C, Bornhäuser M, Thiede C, Taube F, Kramer M, Mohr B, et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol. 2011;29:2758–65.
pubmed: 21632498
Mrózek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP, et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012;30:4515–23.
pubmed: 22987078
pmcid: 3518729
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.
pubmed: 27895058
pmcid: 5291965
Boddu PC, Kadia TM, Garcia-Manero G, Cortes J, Alfayez M, Borthakur G, et al. Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1and FLT3‐internal tandem duplication genotypes. Cancer. 2019;125:1091–1100.
pubmed: 30521114
Harada Y, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, et al. Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study. Leuk Res. 2018;66:20–27.
pubmed: 29360622
Krug U, Berdel WE, Gale RP, Haferlach C, Schnittger S, Muller-Tidow C, et al. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia. Leukemia. 2016;30:1230–6.
pubmed: 26859081
Büchner T, Berdel WE, Haferlach C, Haferlach T, Schnittger S, Müller-Tidow C, et al. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol. 2009;27:61–69.
pubmed: 19047294
Braess J, Amler S, Kreuzer K-A, Spiekermann K, Lindemann HW, Lengfelder E, et al. Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia-a phase 3 study. Leukemia. 2018;32:2558–71.
pubmed: 30275528
pmcid: 6286323
Swerdlow HP, Harris N, Harris NL, Jaffe ES, Pileri SA, Stein H et al. (eds.). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2008.
Schneider F, Hoster E, Unterhalt M, Schneider S, Dufour A, Benthaus T, et al. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS). Blood. 2009;113:5250–3.
pubmed: 19279329
Benthaus T, Schneider F, Mellert G, Zellmeier E, Schneider S, Kakadia PM, et al. Rapid and sensitive screening for CEBPA mutations in acute myeloid leukaemia. Br J Haematol. 2008;143:230–9.
pubmed: 18752591
Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99:4326–35.
pubmed: 12036858
Metzeler K, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Görlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128:686–98.
pubmed: 27288520
Rothenberg-Thurley M, Amler S, Goerlich D, Köhnke T, Konstandin NP, Schneider S, et al. Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia. Leukemia. 2018;32:1598–608.
pubmed: 29472724
pmcid: 6035153
Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.
pubmed: 14673054
Korn EL. Censoring distributions as a measure of follow-up in survival analysis. Stat Med. 1986;5:255–60.
pubmed: 3738291
Blanche P, Dartigues J-F, Jacqmin-Gadda H. Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med. 2013;32:5381–97.
pubmed: 24027076
Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N. Engl J Med. 2016;374:2209–21.
pubmed: 27276561
pmcid: 4979995
Marcucci G, Mrózek K, Ruppert AS, Maharry K, Kolitz JE, Moore JO, et al. Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol. 2005;23:5705–17.
pubmed: 16110030
Brunner AM, Blonquist TM, Sadrzadeh H, Perry AM, Attar EC, Amrein PC, et al. Population-based disparities in survival among patients with core-binding factor acute myeloid leukemia: a SEER database analysis. Leuk Res. 2014;38:773–80.
pubmed: 24793731
pmcid: 4214756
Rücker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119:2114–21.
pubmed: 22186996
Mrózek K, Eisfeld A-K, Kohlschmidt J, Carroll AJ, Walker CJ, Nicolet D, et al. Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically. Leukemia. 2019;33:1620–34.
pubmed: 30737482
pmcid: 6609457
Schlenk RF, Taskesen E, van Norden Y, Krauter J, Ganser A, Bullinger L, et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. 2013;122:1576–82.
pubmed: 23863898
Tallman MS, Wang ES, Altman JK, Appelbaum FR, Bhatt VR, Bixby D, et al. Acute myeloid leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in oncology. J Natl Compr Canc Netw. 2019;17:721–49.
pubmed: 31200351
Prassek VV, Rothenberg-Thurley M, Sauerland MC, Herold T, Janke H, Ksienzyk B, et al. Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged 75 years or older. Haematologica. 2018;103:1853–61.
pubmed: 29903761
pmcid: 6278991
Döhner K, Schlenk RF, Habdank M, Scholl C, Rücker FG, Corbacioglu A, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106:3740–6.
pubmed: 16051734
Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood. 2006;107:4011–20.
pubmed: 16455956
Gaidzik VI, Teleanu V, Papaemmanuil E, Weber D, Paschka P, Hahn J, et al. RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia. 2016;30:2160–8.
pubmed: 27137476
Acharya UH, Halpern AB, Wu QV, Voutsinas JM, Walter RB, Yun S, et al. Impact of region of diagnosis, ethnicity, age, and gender on survival in acute myeloid leukemia (AML). J Drug Assess. 2018;7:51–53.
pubmed: 30034924
pmcid: 6052412
Radkiewicz C, Johansson ALV, Dickman PW, Lambe M, Edgren G. Sex differences in cancer risk and survival: a Swedish cohort study. Eur J Cancer. 2017;84:130–40.
pubmed: 28802709
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. 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. Blood. 2010;116:354–65.
pubmed: 20385793
Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N. Engl J Med. 2017;377:454–64.
pubmed: 28644114
pmcid: 5754190
Stein EM, DiNardo CD, Fathi AT, Mims AS, Pratz KW, Savona MR, et al. Ivosidenib or enasidenib combined with induction and consolidation chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation is safe, effective, and leads to MRD-negative complete remissions. Blood. 2018;132:560.
Döhner H, Dolnik A, Tang L, Seymour JF, Minden MD, Stone RM, et al. Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care. Leukemia. 2018;32:2546–57.
pubmed: 30275526
pmcid: 6286388
Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–9.
pubmed: 25987659
pmcid: 4504945
Wei AH, Strickland SA, Hou J-Z, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019;37:1277–84.
pubmed: 30892988
pmcid: 6524989
DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133:7–17.
pubmed: 30361262
pmcid: 6318429
Lichtenegger FS, Krupka C, Haubner S, Köhnke T, Subklewe M. Recent developments in immunotherapy of acute myeloid leukemia. J Hematol Oncol. 2017;10:142.
pubmed: 28743264
pmcid: 5526264
Winer ES, Stone RM. Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches. Therapeutic Adv Hematol. 2019;10:1–18.
Pastore F, Dufour A, Benthaus T, Metzeler K, Maharry KS, Schneider S, et al. Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2014;32:1586–94.
pubmed: 24711548
pmcid: 4876345
Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Hinai alA, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N. Engl J Med. 2018;378:1189–99.
pubmed: 29601269
Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, et al. Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374:422–33.
pubmed: 26789727
Terwijn M, van Putten WLJ, Kelder A, van der Velden VHJ, Brooimans RA, Pabst T, et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol. 2013;31:3889–97.
pubmed: 24062400
Schuurhuis GJ, Heuser M, Freeman S, Béné M-C, Buccisano F, Cloos J, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD working party. Blood. 2018;131:1275–91.
pubmed: 29330221
pmcid: 5865231