Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% blasts, the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7-2.6]). Patients with 20-29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2-4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non-high risk) with an HR of 3.01 (95%-CI: [1.81-5.00], P < .001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut-off over the 30% cut-off in this cohort. Based on our results, we conclude that a one-phase rather than a two-phase categorization of de novo advanced phase CML patients is appropriate.

Abteilung Hämatologie Onkologie Klinik für Innere Medizin 2 Universitätsklinikum Jena Jena Germany

Chair and Department of Hematology Jagiellonian University Hospital Kraków Poland

Clinic of Hematology CCS and Faculty of Medicine University of Belgrade Belgrade Serbia

Clinical Investigation Center INSERM CIC 1402 CHU Poitiers Poitiers France

Clinical oncology Research department of oncology and hematology Almazov Medical Research Center St Petersburg Russian Federation

Department for Internal Medicine 4 Klinikum Wels Grieskirchen Wels Austria

Department of Hematology Amsterdam University Medical Center location VUmc Amsterdam The Netherlands

Department of Hematology and Oncology L and A University of Bologna Bologna Italy

Department of Hematology Medical University of Gdansk Gdansk Poland

Department of Hematology Oncology University Hospital Palacky University Olomouc Czech Republic

Department of Internal Medicine Department of Medical Science and Division of Hematology University Hospital Uppsala Sweden

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

Helsinki University Hospital Cancer Center and Hematology Research Unit Helsinki University Helsinki Finland

Institute for Medical Information Processing Biometry and Epidemiology Ludwig Maximilians Universität München Munich Germany

Institute of Translational Medicine University of Liverpool Liverpool UK

Munich Cancer Registry Ludwig Maximilians Universität München Munich Germany

National Research Center for Hematology Moscow Russia

Vilnius University Hospital Santaros Klinikos and Institute of Clinical Medicine Vilnius University Vilnius Lithuania

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Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv41-iv51.

Chereda B, Melo JV. Natural course and biology of CML. Ann Hematol. 2015;94(suppl 2):S107-S121.

Fabarius A, Leitner A, Hochhaus A, et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML study IV. Blood. 2011;118:6760-6768.

Wang W, Cortes JE, Tang G, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood. 2016;127:2742-2750.

Branford S, Wang P, Yeung DT, et al. Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease. Blood. 2018;132:948-961.

Grossmann V, Kohlmann A, Zenger M, et al. A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases. Leukemia. 2011;25:557-560.

Soverini S, Hochhaus A, Nicolini FE, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011;118:1208-1215.

Perrotti D, Jamieson C, Goldman J, Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120:2254-2264.

Cortes J. Natural history and staging of chronic myelogenous leukemia. Hematol Oncol Clin North Am. 2004;18:569-584.

Jabbour EJ, Hughes TP, Cortes JE, et al. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia. Leuk Lymphoma. 2014;55:1451-1462.

Cortes JE, Talpaz M, O'Brien S, et al. Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal. Cancer. 2006;106:1306-1315.

Tardieu S, Brun-Strang C, Berthaud P, et al. Management of chronic myeloid leukemia in France: a multicentered cross-sectional study on 538 patients. Pharmacoepidemiol Drug Saf. 2005;14:545-553.

Mottalib MA, Sultana TA, Khalil MI, et al. Phase distribution of chronic myeloid leukemia in Bangladesh. BMC Res Notes. 2014;7:142.

Ahmed R, Naqi N, Hussain I, Khattak BK, Nadeem M, Iqbal J. Presentating phases of chronic myeloid leukemia. J Coll Physicians Surg. 2009;19:469-472.

Hoffmann VS, Baccarani M, Hasford J, et al. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia. 2017;31:593-601.

Faber E, Muzik J, Koza V, et al. Treatment of consecutive patients with chronic myeloid leukemia in the cooperating centers from The Czech Republic and the whole of Slovakia after 2000--a report from the population-based CAMELIA Registry. Eur J Haematol. 2011;87:157-168.

Kantarjian H, Talpaz M, O'Brien S, et al. Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia--comparison with historic experience. Cancer. 2005;103:2099-2108.

Hehlmann R, Saussele S, Voskanyan A, et al. Management of CML-blast crisis. Best Pract Res Clin Haematol. 2016;29:295-307.

Sokal J, Cox E, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63:789-799.

Hasford J, Pfirrmann M, Hehlmann R, 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;90:850-858.

Hasford J, Baccarani M, Hoffmann V, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118:686-692.

Pfirrmann M, Baccarani M, Saussele S, et al. Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia. 2016;30:48-56.

Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872-884.

Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19:716-723.

Hoffmann VS, Baccarani M, Lindoerfer D, et al. The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib. Leukemia. 2013;27:2016-2022.

Hoffmann VS, Baccarani M, Hasford J, et al. The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries. Leukemia. 2015;29:1336-1343.

Palandri F, Castagnetti F, Alimena G, et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML working party experience after a 7-year follow-up. Haematologica. 2009;94:205-212.

Jiang Q, Xu LP, Liu DH, et al. Imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in the accelerated phase. Blood. 2011;117:3032-3040.

Ohanian M, Kantarjian HM, Quintas-Cardama A, et al. Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid leukemia in accelerated phase. Clin Lymphoma Myeloma Leuk. 2014;14:155-162 e151.

Söderlund S, Dahlen T, Sandin F, et al. Advanced phase chronic myeloid leukemia (CML) in the tyrosine kinase inhibitor era - a report from the Swedish CML register. Eur J Haematol. 2017;98:57-66.

Hehlmann R, Lauseker M, Saussele S, 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;31:2398-2406.

Jain P, Kantarjian HM, Ghorab A, et al. Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: cohort study of 477 patients. Cancer. 2017;123:4391-4402.

Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-2405.

Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292-2302.

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

Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations

Deep Molecular Response Achieved with Chemotherapy, Dasatinib and Interferon α in Patients with Lymphoid Blast Crisis of Chronic Myeloid Leukaemia

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia