KLINIČKE KARAKTERISTIKE I PREŽIVLJAVANJE ODRASLIH PACIJENATA OBOLELIH OD AKUTNE MIJELOIDNE LEUKEMIJE: ISKUSTVO JEDNOG CENTRA
Preživljavanje pacijenata obolelih od akutne mijeloidne leukemije
Sažetak
Uvod/Cilj: Akutna mijeloidna leukemija (AML) je heterogena bolest, po svojim biološkim karakteristikama i po odgovoru na terapiju. Brojni prognostički faktori pri dijagnozi koji su u vezi sa samom bolešću kod pacijenta, terapija i odgovor na terapiju utiču na ishod AML-a. Uprkos velikoj stopi postizanja kompletne remisije, ukupno preživljavanje (engl. overall survival – OS) je i dalje loše. Cilj ovog istraživanja je da se odredi kliničko-biološki profil bolesnika sa AML-om i njegov prognostički uticaj na stopu OS i preživljavanje bez znakova bolesti (engl. disease-free survival – DFS).
Materijali i metode: Retrospektivna analiza obuhvatila je 271 bolesnika sa dijagnozom akutne mijeloidne leukemije postavljenom na Klinici za hematologiju, Univerzitetskog kliničkog centra Srbije (UKCS), između januara 2018. i januara 2023. godine. Analizirani su demografski parametri, ECOG PS (engl. Eastern Cooperative Oncology Group performance status), komorbiditeti, parametri laboratorijske analize i hematološke dijagnostike AML-a, kao potencijalni faktori rizika za OS i DFS, uz korišćenje univarijantnog Koksovog regresionog modela.
Rezultati: Od ukupno 271 pacijenta, 206 (76%) je lečeno intenzivnom hemioterapijom, od kojih je bilo 108 muškaraca i 98 žena. Prosečna starost ovih ispitanika je bila 50,3 godine. Prema klasifikaciji rizika Evropske mreže za leukemiju (engl. European LeukemiaNet – ELN), najviše je bilo bolesnika intermedijarnog stepena rizika, odnosno 128 (62,1%) pacijenata. Najzastupljeniji podtip AML-a je bio NOS AML (engl. AML not otherwise specified), prisutan kod 123 (59,7%) bolesnika. Univarijantna analiza je pokazala da su starost od ≥ 60 godina (p = 0,009) i vrednost Le ≥ 30 x 109/l (p = 0,031) nepovoljni prognostički parametri za OS. Podtip AML-a, MRC (engl. myelodysplasia-related changes) bio je najznačajniji faktor rizika za kraće preživljavanje bez znakova bolesti (p = 0,027).
Zaključak: U analiziranoj grupi bolesnika sa AML-om lečenih intenzivnom terapijom, pokazali smo nisku stopu OS, kao i da godine starosti i MRC podtip AML-a predstavljaju nepovoljne faktore rizika za kraće ukupno preživljavanje, odnosno preživljavanje bez znakova bolesti.
Reference
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 Jun 9;374(23):2209-21. doi: 10.1056/NEJMoa1516192.
Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018 Aug 18;392(10147):593-606. doi: 10.1016/S0140-6736(18)31041-9.
Virijevic M, Kraguljac-Kurtovic N, Mitrovic M, Jakovic L, Bukumuric Z, Pantic N, et al. Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia. Hematol Oncol. 2024 Mar;42(2):e3253. doi: 10.1002/hon.3253.
SEER Cancer Stat Facts: Leukemia – Acute Myeloid Leukemia (AML) [Internet]. Bethesda (MD): National Cancer Institute (US). [date unknown] – [cited 2024 Jan 10] Available from: https://seer.cancer.gov/statfacts/html/amyl.html
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 May 19;12 (20):2391-405. doi: 10.1182/blood-2016-03-643544.
Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022 Jul;36(7):1703-19. doi: 10.1038/s41375-022-01613-1.
Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022 Sep 22;140(12):1345-77. doi: 10.1182/blood.2022016867.
Bullinger L, Döhner K, Döhner H. Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol. 2017 Mar 20;35(9):934-46. doi: 10.1200/JCO.2016.71.2208.
Short NJ, Zhou S, Fu C, Berry DA, Walter RB, Freeman SD, et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol. 2020 Dec 1;6(12):1890-9. doi: 10.1001/jamaoncol.2020.4600.
Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015 Sep 17;373(12):1136-52. doi: 10.1056/NEJMra1406184.
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 Jan 26;129(4):424-47. doi: 10.1182/blood-2016-08-733196.
Récher C, Röllig C, Bérard E, Bertoli S, Dumas PY, Tavitian S, et al. Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries. Leukemia. 2022 Apr;36(4):913-22. doi: 10.1038/s41375-021-01425-9.
Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021 Feb 22;11(2):41. doi: 10.1038/s41408-021-00425-3.
Wei AH, Strickland SA Jr, Hou JZ, 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 May 20;37(15):1277-84. doi: 10.1200/JCO.18.01600.
DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020 Aug 13;383(7):617-29. doi: 10.1056/NEJMoa2012971.
Thol F, Döhner H, Ganser A. How I treat refractory and relapsed acute myeloid leukemia. Blood. 2024 Jan 4;143(1):11-20. doi: 10.1182/blood.2023022481.
McGowan-Jordan J, Hastings RJ, Moore S, editors. ISCN 2020: An International System for Human Cytogenomic Nomenclature. Basel: Karger; 2020.
Béné MC, Nebe T, Bettelheim P, Buldini B, Bumbea H, Kern W, et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia. 2011 Apr;25(4):567-74. doi: 10.1038/leu.2010.312.
Kiyoi H, Naoe T, Yokota S, Nakao M, Minami S, Kuriyama K, et al. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia. 1997 Sep;11(9):1447-52. doi: 10.1038/sj.leu.2400756.
Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al; GIMEMA Acute Leukemia Working Party. Cytolasmatic nucleophosmin in acute myelogenous leukemia with normal karyotype. N Engl J Med. 2005 Jan 20;352(3):254-66. doi: 10.1056/NEJMoa041974.
Kraan J, Gratama JW, Haioun C, Orfao A, Plonquet A, Porwit A, et al. Flow cytometric immunophenotyping of cerebrospinal fluid. Curr Protoc Cytom. 2008 Jul; Chapter 6: Unit 6.25. doi: 10.1002/0471142956.cy0625s45.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55.
Sorror ML, Marris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoetic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogenic HCT. Blood. 2005 Oct 15;106(8): 2912-9. doi: 10.1182/blood-2005-05-2004.
Sasaki K, Ravandi F, Kadia TM, DiNardo CD, Short NJ, Borthakur G, et al. De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer. 2021 Jun 15;127(12):2049-61. doi: 10.1002/cncr.33458.
Gbadamosi B, Ezekwudo D, Bastola S, Jaiyesimi I. Predictive and prognostic markers in adults with acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma Leuk. 2018 Jul;18(7):e287-94. doi: 10.1016/j.clml.2018.05.005.
Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. Age and acute myeloid leukemia. Blood. 2006 May 1;107(9):3481-5. doi: 10.1182/blood-2005-09-3724.
Etienne A, Esterni B, Charbonnier A, Mozziconacci MJ, Arnoulet C, Coso D, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer. 2007 Apr 1;109(7):1376-83. doi: 10.1002/cncr.22537.
Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000 Dec 15;96(13):4075-83.
Karami K, Akbari M, Moradi MT, Soleymani B, Fallahi H. Survival prognostic factors in patients with acute myeloid leukemia using machine learning techniques. PLoS One. 2021 Jul 21;16(7):e0254976. doi: 10.1371/journal.pone.0254976.
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 Oct 10; 26(29):4791-7. doi: 10.1200/JCO.2008.16.0259.
Pravdić Z, Suvajdžić Vuković N, Virijević M, Mitrović M, Pantić N, Sabljić N, et al. Can pharmacogenetics impact the therapeutic effect of cytarabine and anthracyclines in adult acute myeloid leukaemia patients?: A Serbian experience. J Med Biochem. 2024;43(4):545-55. doi: 10.5937/jomb0-47459.
Othus M, Kantarjian H, Petersdorf S, Ravandi F, Godwin J, Cortes J, et al. Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson. Leukemia. 2014 Feb;28(2):289-92. doi: 10.1038/leu.2013.176.
Kayal S, Sengar M, Jain H, Bonda A, George B, Kulkarni OP. et al. Induction related mortality in acute myeloid leukemia: multivariate model of predictive score from the Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC). Blood. 2019 Nov 13;134(Suppl 1):2615. doi: 10.1182/blood-2019-127623.
Ganzel C, Sun Z, Cripe LD, Fernandez HF, Douer D, Rowe JM, et al. Very poor long-term survival in past and more recent studies for relapsed AML patients: The ECOG-ACRIN experience. Am J Hematol. 2018 Aug;93(8):1074-81. doi: 10.1002/ajh.25162.
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 Aug 3;377(5):454-64. doi: 10.1056/NEJMoa1614359.
Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-9. doi: 10.3324/haematol.2018.188888.
Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, et al. CPX-351 versus 7+ 3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-91. doi: 10.1016/S2352-3026(21)00134-4.
Wang L, Chu X, Wang J, An L, Liu Y, Li L, et al. Clinical characteristics and optimal therapy of acute myeloid leukemia with myelodysplasia-related-changes: a retrospective analysis in a cohort of Chinese patients. Turk J Haematol. 2021 Aug 25;38(3):188-94. doi: 10.4274/tjh.galenos.2021.2021.0009.
