The EUTOS Long-Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range, 1 month to 6 years) progression and/or death (whichever came first) occurred in 23 patients. For the entire cohort of patients the 5-year progression-free survival rate was 92% (95% CI: 87%-94%) and the 5-year survival accounting for chronic myeloid leukemia deaths was 97% (95% CI: 94%-99%). Of the 309 patients allocated to low (n=199), intermediate (n=68) and high (n=42) risk groups by the EUTOS Long-Term Survival score, events (progression and/or death) occurred in 6.0%, 8.8% and 26.2%, respectively. Estimates of the 5-year progression-free survival rates according to these three risk groups were 96% (95% CI: 92%-98%), 88% (95% CI: 76%-95%) and 67% (95% CI: 48%-81%), respectively. Differences in progression-free survival according to these risk groups were highly significant (P<0.0001, overall). The EUTOS Long-Term Survival score showed better differentiation of progression-free survival than the Sokal (<45 years), Euro and EUTOS scores in children and adolescents with chronic myeloid leukemia and should be considered in therapeutic algorithms. (Trial registered at: www.clinicaltrials.gov NCT01281735).

Children's Cancer Research Institute and St Anna Children's Hospital Vienna Austria

Department of Pediatric Hematology Oncology and Transplantation Wroclaw Medical University Poland

Department of Pediatric Hematology Oncology Immunology and Medical Genetics Clinical Hospital Split Croatia

Department of Pediatric Hematology Oncology University Hospital Motol Charles University Prague Czech Republic

Department of Pediatric Hematology Robert Debré Hospital Paris France

Department of Pediatric Hematology Uludağ University Hospital Görükle Bursa Turkey

Department of Pediatric Oncology Hematology University Medical Center Groningen University of Groningen the Netherlands and Dutch Childhood Oncology Group the Hague the Netherlands

Department of Pediatric Oncology of University Children's Hospital Bratislava Slovakia

Department of Pediatrics Ghent University Hospital Belgium

Department of Pediatrics Prince of Wales Hospital The Chinese University of Hong Kong China

Department of Pediatrics Rigshospitalet University Hospital Copenhagen Denmark

Department of Pediatrics Saint George Hospital University Medical Center Beirut Lebanon

Department of Pediatrics University Hospital Carl Gustav Carus Dresden Germany

Department of Pediatrics University of Milano Bicocca San Gerardo Hospital Fondazione MBBM Monza Italy

Inserm CIC 1402 University Hospital Poitiers France

Zobrazit více v PubMed

Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in good-risk chronic granulocytic leukemia. Blood. 1984;63(4):789–799. PubMed

Hasford J, Pfirmann M, Hehlman R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alpha. J Natl Cancer Inst. 1998;90(11):850–858. PubMed

Hasford J, Baccarani M, Hoffman 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(3):686–692. PubMed

Sokal JE, Baccarani M, Tura S, et al. Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation. Blood. 1985;66(6):1352–1357. PubMed

Gurrea Salas D, Glauche I, Tauer JT, et al. Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients? Ann Hematol. 2015;9(8):1363–1371. PubMed

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(1):48–56. PubMed

Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Blood. 2013;122(6):872–884. PubMed PMC

Guilhot J, Baccarani M, Clark RE, et al. Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet. Blood. 2012;119(25):5963–5971. PubMed

Gray RJ. A class of k-samples tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16(3):1141–1154.

Castagnetti F, Gugliotta G, Baccarani M, et al. Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 2015;26(1):185–192. PubMed

Kalmanti L, Saussele S, Lauseker M, et al. Younger patients with chronic myeloid leukemia do well in spite of poor prognostic indicators: results from the randomized CML study IV. Ann Hematol. 2014;93(1):71–80. PubMed PMC

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(6):1336–1343. PubMed

Oyekunle AA, Osho PO, Aneke JC, et al. The predictive value of the Sokal and Hasford scoring systems in chronic myeloid leukemia in the imatinib era. J Hemat Malign. 2012;2(2):25–32.

Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851–2857. PubMed

Hehlmann R, Müller MC, Lauseker M, et al. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-Study IV. J Clin Oncol. 2014;32(5):415–423. PubMed

Millot F, Baruchel A, Guilhot J, et al. Imatinib is effective in children with previously untreated chronic myelogenous leukemia in early chronic phase: results of the French national phase IV trial. J Clin Oncol. 2011;29(20):2827–2832. PubMed

Millot F, Guilhot J, Baruchel A, et al. Impact of early molecular response in children with chronic myeloid leukemia treated in the French Glivec phase 4 study. Blood. 2014;124(15):2408–2410. PubMed

Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-α in newly diagnosed chronic myeloid leukemia. J Clin Oncol. 2011;29(12):1634–1642. PubMed

Hoffmann VS, Baccarani M, Hasford J, et al. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia. 2017;31(3):593–601. PubMed

De la Fuente J, Baruchel A, Biondi A, et al. How I manage CML in children - guidelines for the management of chronic myeloid leukaemia in children and young people up to the age of 18 years. Br J Haematol. 2014;167(1):33–47. PubMed

Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34(20):2333–2340. PubMed PMC

Hochhaus A, Saglio G, Hughes TP, 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(5):1044–1054. PubMed PMC

Pemmaraju N, Kantarjian H, Shan J, et al. Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy. Haematologica. 2012;97(7):1029–1035. PubMed PMC

Sasaki K, Strom S, O’Brien S, et al. Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol. 2015;2(5):e186–e193. PubMed PMC

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

Prevalence of anemia at diagnosis of pediatric chronic myeloid leukemia and prognostic impact on the disease course

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

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01281735