Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.

3 Medizinische Klinik Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Universität Heidelberg Mannheim Germany

Abteilung für Innere Medizin 4 Klinikum Wels Grieskirchen Wels Austria

Almazov Medical Reseach Centre Institute of Oncology and Hematology St Petersburg Russian Federation

Clinic of Hematology Clinical Center of Serbia Faculty of Medicine University of Belgrade Belgrade Serbia

Clinical Department of Hematology and Oncology L and A Seragnoli S Orsola Malpighi Hospital University of Bologna Bologna Italy

Clinical Investigation Centre INSERM CIC 1402 CHU Poitiers Poitiers France

Department of Hemato Oncology Faculty Hospital Olomouc Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Hematology Jagiellonian Unversity Medical College Kraków Poland

Department of Hematology University Medical Centre Ljubljana Slovenia

Department of Hematology VU University Medical Center Amsterdam Netherlands

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Masaryk University Brno Czech Republic

Department of Medical Sciences University of Uppsala and Section of Hematology Uppsala University Hospital Uppsala Sweden

Department of Molecular and Clinical Cancer Medicine University of Liverpool Liverpool UK

ELN Foundation Weinheim Germany

Hematology Department Hospital Clinic IDIBAPS Barcelona Spain

Hematology Research Unit Helsinki University of Helsinki and Department of Hematology Helsinki University Hospital Comprehensive Cancer Center Helsinki Finland

Institut für Medizinische Informationsverarbeitung Biometrie und Epidemiologie IBE Ludwig Maximilians Universität Munich Germany

Institute of Clinical Medicine Vilnius University Vilnius Lithuania

Institution of Medical Sciences University of Uppsala Uppsala Sweden

Klinik für Innere Medizin 2 Universitätsklinikum Jena Jena Germany

Medical University of Gdansk Gdansk Poland

National Research Center for Hematology Ministry of Healthcare of the Russian Federation Moscow Russian Federation

Romanian Academy of Medical Sciences and Medical University Bucharest Romania

School of Medicine University of Zagreb Zagreb Croatia

Tartu University Hospital Tartu Estonia

See more in PubMed

Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966–84. doi: 10.1038/s41375-020-0776-2. PubMed DOI PMC

Pfirrmann M, Lauseker M, Hoffmann VS, Hasford J. Prognostic scores for patients with chronic myeloid leukemia under particular consideration of competing causes of death. Ann Hematol. 2015;94:S209–18. doi: 10.1007/s00277-015-2316-0. PubMed DOI

Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63:789–99. doi: 10.1182/blood.V63.4.789.789. PubMed DOI

Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850–8. doi: 10.1093/jnci/90.11.850. PubMed DOI

Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118:686–92. doi: 10.1182/blood-2010-12-319038. PubMed DOI

Pfirrmann M, Baccarani M, Saussele S, Guilhot J, Cervantes F, Ossenkoppele G, et al. Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia. 2016;30:48–56. doi: 10.1038/leu.2015.261. PubMed DOI

Hehlmann R, Lauseker M, Saussele S, Pfirrmann M, Krause S, Kolb HJ, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017;31:2398–406. doi: 10.1038/leu.2017.253. PubMed DOI PMC

Molica M, Colafigli G, Scalzulli E, Alunni Fegatelli D, Chiatamone Ranieri S, Rizzo L, et al. Ten-year outcome of chronic-phase chronic myeloid leukemia patients treated with imatinib in real life. Ann Hematol. 2019;98:1891–904. doi: 10.1007/s00277-019-03706-x. PubMed DOI

Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N. Engl J Med. 2017;376:917–27. doi: 10.1056/NEJMoa1609324. PubMed DOI PMC

Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30:1044–54. doi: 10.1038/leu.2016.5. PubMed DOI PMC

Brummendorf TH, Cortes JE, de Souza CA, Guilhot F, Duvillie L, Pavlov D, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br J Haematol. 2015;168:69–81. doi: 10.1111/bjh.13108. PubMed DOI PMC

Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:612–21. doi: 10.1016/S1470-2045(16)00080-2. PubMed DOI

Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol. 2018;36:231–7. doi: 10.1200/JCO.2017.74.7162. PubMed DOI PMC

Hoffmann VS, Baccarani M, Lindoerfer D, Castagnetti F, Turkina A, Zaritsky A, et al. The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib. Leukemia. 2013;27:2016–22. doi: 10.1038/leu.2013.171. PubMed DOI

Hoffmann VS, Baccarani M, Hasford J, Castagnetti F, Di Raimondo F, Casado LF, et al. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia. 2017;31:593–601. doi: 10.1038/leu.2016.246. PubMed DOI

Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84. doi: 10.1182/blood-2013-05-501569. PubMed DOI PMC

Therneau TM, Grambsch PM. Modeling Survival Data: Extending the Cox Model. New York, USA: Springer; 2000.

Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. New York, USA: Wiley; 1980.

Choudhury JB. Non-Parametric confidence interval estimation for competing risks analysis: application to contraceptive data. Stat Med. 2002;21:1129–44. doi: 10.1002/sim.1070. PubMed DOI

Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. doi: 10.1080/01621459.1999.10474144. DOI

Wolbers M, Blanche P, Koller MT, Witteman JC, Gerds TA. Concordance for prognostic models with competing risks. Biostatistics. 2014;15:526–39. doi: 10.1093/biostatistics/kxt059. PubMed DOI PMC

Lauseker M, Zu Eulenburg C. Analysis of cause of death: competing risks or progressive illness-death model? Biom J. 2019;61:264–74. doi: 10.1002/bimj.201700238. PubMed DOI

de Wreede LC, Fiocco M, Putter H. The mstate package for estimation and prediction in non- and semi-parametric multi-state and competing risks models. Comput Meth Prog Bio. 2010;99:261–74. doi: 10.1016/j.cmpb.2010.01.001. PubMed DOI

Geelen IGP, Sandin F, Thielen N, Janssen J, Hoogendoorn M, Visser O, et al. Validation of the EUTOS long-term survival score in a recent independent cohort of “real world” CML patients. Leukemia. 2018;32:2299–303. doi: 10.1038/s41375-018-0136-7. PubMed DOI

Yang X, Bai Y, Shi M, Zhang W, Niu J, Wu C, et al. Validation of the EUTOS long-term survival score in Chinese chronic myeloid leukemia patients treated with imatinib: a multicenter real-world study. Cancer Manag Res. 2020;12:1293–301. doi: 10.2147/CMAR.S237467. PubMed DOI PMC

Millot F, Guilhot J, Suttorp M, Gunes AM, Sedlacek P, De Bont E, et al. Prognostic discrimination based on the EUTOS long-term survival score within the International Registry for Chronic Myeloid Leukemia in children and adolescents. Haematologica. 2017;102:1704–8. doi: 10.3324/haematol.2017.170035. PubMed DOI PMC

Sokal JE, Baccarani M, Tura S, Fiacchini M, Cervantes F, Rozman C, et al. Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation. Blood. 1985;66:1352–7. doi: 10.1182/blood.V66.6.1352.1352. PubMed DOI

Castagnetti F, Gugliotta G, Breccia M, Stagno F, Specchia G, Levato L, et al. The use of EUTOS long-term survival score instead of sokal score is strongly advised in elderly chronic myeloid leukemia patients. Blood. 2018;132:44. doi: 10.1182/blood-2018-99-117409. DOI

Lauseker M, Bachl K, Turkina A, Faber E, Prejzner W, Olsson-Stromberg U, et al. Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin. Am J Hematol. 2019;94:1236–43. doi: 10.1002/ajh.25628. PubMed DOI

Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N. Engl J Med. 2010;362:2251–9. doi: 10.1056/NEJMoa0912614. PubMed DOI

Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl J Med. 2010;362:2260–70. doi: 10.1056/NEJMoa1002315. PubMed DOI

Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boque C, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naive chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333–40. doi: 10.1200/JCO.2015.64.8899. PubMed DOI PMC

Baccarani M, Abruzzese E, Accurso V, Albano F, Annunziata M, Barulli S, et al. Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP. Blood Adv. 2019;3:4280–90. doi: 10.1182/bloodadvances.2019000865. PubMed DOI PMC

Radich JP, Deininger M, Abboud CN, Altman JK, Berman E, Bhatia R, et al. Chronic myeloid leukemia, version 1.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2018;16:1108–35. doi: 10.6004/jnccn.2018.0071. PubMed DOI

Hochhaus A, Saussele S, Rosti G, Mahon F-X, Janssen JJWM, Hjorth-Hansen H, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv41–51. doi: 10.1093/annonc/mdx219. PubMed DOI

Claudiani S, Apperley JF. The argument for using imatinib in CML. Hematol Am Soc Hematol Educ Program. 2018;2018:161–7. doi: 10.1182/asheducation-2018.1.161. PubMed DOI PMC

Hantel A, Larson RA. Imatinib is still recommended for frontline therapy for CML. Blood Adv. 2018;2:3648–52. doi: 10.1182/bloodadvances.2018018614. PubMed DOI PMC

Mogensen UB, Ishwaran H, Gerds TA. Evaluating random forests for survival analysis using prediction error curves. J Stat Softw. 2012;50:1–23. doi: 10.18637/jss.v050.i11. PubMed DOI PMC

Allignol A, Schumacher M, Beyersmann J. Empirical transition matrix of multi-state models: The etm package. J Stat Softw. 2011;38:1–15. doi: 10.18637/jss.v038.i04. DOI

2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry