Abstract
Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by a dismal outcome. To enable better outcomes, it is necessary to develop individual therapies based on risk stratification. In the present study, we established two new comprehensive prognostic scoring systems (CPSS) for overall survival (OS) and relapse-free survival (RFS) using the Cox proportional hazards regression, CPSS integrated and weighted age, AML type, lactic dehydrogenase (LDH), ECOG score, cytogenetics, and gene mutations. We divided patients into three risk groups—low-, intermediate-, and high-risk—with 1-year OS rates of 100.0%, 82.9%, and 38.2%, respectively (p < 0.0001), and patients undergoing complete remission (CR) were also separated into low-risk, intermediate-risk, and high-risk groups, with 1-year RFS rates of 87.7%, 58.4%, and 30.2%, respectively (p < 0.0001). We conclude that CPSS that integrate clinical characteristics, cytogenetic abnormalities, and gene mutations may improve the stratification of AML patients.
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References
Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018;392(10147):593–606.
Döhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015;373(12):1136–52.
Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–89.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–406.
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(4):424–47.
O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, et al. Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15(7):926–57.
Patel U, Luthra R, Medeiros LJ, Patel KP. Diagnostic, prognostic, and predictive utility of recurrent somatic mutations in myeloid neoplasms. Clin Lymphoma Myeloma Leuk. 2017;17(July):S62–74.
Larsson CA, Cote G, Quintás-Cardama A. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol Cancer Res. 2013;11(8):815–27.
Rafael B. Splicing factor mutations in cancer. In: Yeo GW, editor. RNA processing, vol. 907. Switzerland: Springer; 2016. p. 215–28.
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(23):2209–21.
Ahn J-S, Kim H-J, Kim Y-K, Lee S-S, Ahn S-Y, Jung S-H, et al. Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype. Oncotarget. 2017;9(4):4961–8.
Djunic I, Suvajdzic-Vukovic N, Virijevic M, Novkovic A, Colovic N, Vidovic A, et al. Prognostic risk score for the survival of elderly patients with acute myeloid leukaemia comprising comorbidities. Med Oncol. 2013;30(1):394.
Wheatley K, Brookes CL, Howman AJ, Goldstone AH, Milligan DW, Prentice AG, et al. Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials. Br J Haematol. 2009;145(5):598–605.
Malfuson JV, Etienne A, Turlure P, de Revel T, Thomas X, Contentin N, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica. 2008;93(12):1806–13.
Wiese M, Daver N. Unmet clinical needs and economic burden of disease in the treatment landscape of acute myeloid leukemia. Am J Manag Care. 2018;24(16 Suppl):S347–55.
Bullinger L, Döhner K, Döhner H. Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 2017;35(9):934–46.
Østgård LSG, Medeiros BC, Sengeløv H, Nørgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33(31):3641–9.
Kuykendall A, Duployez N, Boissel N, Lancet JE, Welch JS. Acute myeloid leukemia: the good, the bad, and the ugly. Am Soc Clin Oncol Educ B. 2018;23(38):555–73.
Teng CL, Young JH, Hsu SL, Chou G, Kuo IT, Yu CY, et al. Lactate dehydrogenase, not vascular endothelial growth factor or basic fibroblast growth factor, positively correlates to bone marrow vascularity in acute myeloid leukemia. J Chin Med Assoc. 2006;69(11):534–7.
Röllig C, Thiede C, Gramatzki M, Aulitzky W, Bodenstein H, Bornhäuser M, et al. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood. 2010;116(6):971–8.
Basiricò R, Pirrotta R, Fabbiano F, Mirto S, Cascio L, Pagano M, et al. Submicroscopic deletions at 7q region are associated with recurrent chromosome abnormalities in acute leukemia. Haematologica. 2003;88(4):429–37.
Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29):4791–7.
Nazha A, Kantarjian HM, Bhatt VR, Nogueras-Gonzalez G, Cortes JE, Kadia T, et al. Prognostic implications of chromosome 17 abnormalities in the context of monosomal karyotype in patients with acute myeloid leukemia and complex cytogenetics. Clin Lymphoma Myeloma Leuk. 2014;14(2):163–71.
Poiré X, Labopin M, Maertens J, Yakoub-Agha I, Blaise D, Ifrah N, et al. Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2018;103(2):256–65.
Pastore F, Dufour A, Benthaus T, Metzeler KH, 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(15):1586–94.
Malagola M, Skert C, Vignetti M, Piciocchi A, Martinellli G, Alimena G, et al. A simple prognostic scoring system for newly diagnosed cytogenetically normal acute myeloid leukemia: retrospective analysis of 530 patients. Leuk Lymphoma. 2011;52(12):2329–35.
Lin P-H, Li H-Y, Fan S-C, Yuan TH, Chen M, Hsu Y-H, et al. A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice. Cancer Med. 2017;6(2):349–60.
Stölzel F, Pfirrmann M, Aulitzky WE, Kaufman M, Bodenstein H, Bornhäuser M, et al. Risk stratification using a new prognostic score for patients with secondary acute myeloid leukemia: results of the prospective AML96 trial. Leukemia. 2011;25(3):420–8.
Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378(13):1189–99.
Hoskins AA, Moore MJ. The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem Sci. 2012;37(5):179–88.
Zhou J, Chng WJ. Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia. Stem Cell Investig. 2017;4:6.
Yohe S. Molecular genetic markers in acute myeloid leukemia. J Clin Med. 2015;4(3):460–78.
Ayatollahi H, Shajiei A, Sadeghian MH, Sheikhi M, Yazdandoust E, Ghazanfarpour M, et al. Prognostic importance of C-KIT mutations in core binding factor acute myeloid leukemia: a systematic review. Hematol Oncol Stem Cell Ther. 2017;10(1):1–7.
Chen W, Xie H, Wang H, Chen L, Sun Y, Chen Z, et al. Prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia: a systematic review and meta-analysis. PLoS One. 2016;11(1):1–19.
Manara E, Bisio V, Masetti R, Beqiri V, Rondelli R, Menna G, et al. Core-binding factor acute myeloid leukemia in pediatric patients enrolled in the AIEOP AML 2002/01 trial: screening and prognostic impact of c-KIT mutations. Leukemia. 2014;28(5):1132–4.
Krauth MT, Eder C, Alpermann T, Bacher U, Nadarajah N, Kern W, et al. High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome. Leukemia. 2014;28(7):1449–58.
Qin Y-Z, Zhu H-H, Jiang Q, Xu L-P, Jiang H, Wang Y, et al. Heterogeneous prognosis among KIT mutation types in adult acute myeloid leukemia patients with t(8;21). Blood Cancer J. 2018;8(8):76.
Acknowledgements
We thank the Laboratory Department, the Medical Records Department, the Yuanqi Biopharmaceutical Technology Co. Ltd. (Shanghai, China), and all the clinical departments for providing us with the clinical and laboratory information on patients. This work was supported by the National Natural Science Foundation of China under Grant number 81570116, and 81873434.
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Supplementary material 1 (PDF 1025 kb): The Kaplan–Meier Curves for cytogenetic normal AML Patients’ OS and RFS with Survival Data According to the PINA
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Zhou, F., Zhou, F., Du, M. et al. Comprehensive prognostic scoring systems could improve the prognosis of adult acute myeloid leukemia patients. Int J Hematol 110, 575–583 (2019). https://doi.org/10.1007/s12185-019-02721-y
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DOI: https://doi.org/10.1007/s12185-019-02721-y