Effectiveness of Three Prognostic Scoring Systems in Predicting the Response and Outcome in Pediatric Chronic Myeloid Leukemia Chronic Phase on Frontline Imatinib

Abstract

Introduction: The Sokal and Hasford (Euro) scores were developed in the chemotherapy and interferon eras and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, European Treatment and Outcome Study (EUTOS) scoring system was introduced. Data on risk stratification in pediatric CML population was lacking due to its rarity (<3%). Objective: To study the effectiveness in predicting the response and outcome with three prognostic scores in pediatric CML-chronic phase patients on front line Imatinib. Materials and Methods: We retrospectively analyzed the hospital records of newly diagnosed CML CP patients (aged ≤18 years) from 2006 to 2010 for their risk score, cytogenetic response at 18 months and event free survival (EFS) at the end of 4 years. Events include loss of hematological response, loss of cytological response, progression to accelerated/blast phase (AP/BC). All received free Imatinib under Gleevac international patient assistance program. Results: Data of 106 children was analyzed with median age of 13.5 (ranged 5-18 years) and male preponderance (M:F = 1.14:1). The distribution of children was 63%, 32% and 5% in Sokal low, intermediate and high risk respectively, 50%, 43% and 5% in Hasford/Euro low, intermediate and high risk respectively, 71% and 29% in EUTOS low and high risk respectively. The overall cumulative complete hematological response at the end of 3 month was 94%, and complete cytogenetic response at 12 months was 75%. The CCyR at 18 month was seen in 90%,74% and 83% among Sokal low, intermediate and high risk groups respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk groups respectively, 84% and 86% EUTOS low and high risk groups respectively. The EFS at the end of 48 months was seen in 87%,79% and 83% among Sokal low, intermediate and high risk groups respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk groups respectively, 86% and 80% EUTOS low and high risk groups respectively. Conclusion: None of the scoring systems predicted the response and outcome effectively in children with CML CP on front line Imatinib.

Keywords

Chronic myeloid leukemia chronic phase - Euro score - European Treatment and Outcome Study score and cytogenetic response - imatinib - Sokal score

• References

• 1 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.
• 2 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.
• 3 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.
• 4 Lakshmaiah KC, Bhise R, Purohit S, Abraham LJ, Lokanatha D, Suresh TM, et al. Chronic myeloid leukemia in children and adolescents: Results of treatment with imatinib mesylate. Leuk Lymphoma 2012;53:2430-3.
• 5 Hu B, Savani BN. Impact of risk score calculations in choosing front-line tyrosine kinase inhibitors for patients with newly diagnosed chronic myeloid leukemia in the chronic phase. Eur J Haematol 2014;93:179-86.
• 6 Linga VG, Ganta RR, Kalpathi KI, Gundeti S, Rajappa SJ, Digumarti R, et al. Response to imatinib mesylate in childhood chronic myeloid leukemia in chronic phase. South Asian J Cancer 2014;3:203-5.
• 7 Babu GK, Thanky A, Jacob LA, Suresh Babu MC, Dasappa L, Ganguly S. Outcome of young adults with chronic myeloid leukemia treated with upfront imatinib: A single institutional experience. J Appl Hematol 2015;6:157-61.
• 8 Suttorp M, Millot F. Treatment of pediatric chronic myeloid leukemia in the year 2010: Use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology Am Soc Hematol Educ Program 2010;2010:368-76.
• 9 Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: An update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041-51.
• 10 Gurrea Salas D, Glauche I, Tauer JT, Thiede C, Suttorp M. Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients? Ann Hematol 2015;94:1363-71.
• 11 Marin D, Ibrahim AR, Goldman JM. European Treatment and Outcome Study (EUTOS) score for chronic myeloid leukemia still requires more confirmation. J Clin Oncol 2011;29:3944-5.
• 12 Breccia M, Finsinger P, Loglisci G, Latagliata R, Mancini M, Salaroli A, et al. The EUTOS score identifies chronic myeloid leukeamia patients with poor prognosis treated with imatinib first or second line. Leuk Res 2012;36:e209-10.
• 13 Feng G, Wang J, Jiang Y, Li Y, Ding M, Wang N, et al. Clinical significance of Sokal, Hasford and EUTOS prognostic scoring systems in chronic myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi 2014;35:743-6.
• 14 Yahng SA, Jang EJ, Choi SY, Oh YJ, Bang JH, Park JE, et al. Comparison of Sokal, Hasford and EUTOS scores in terms of long-term treatment outcome according to the risks in each prognostic model: A single center data analyzed in 255 early chronic phase chronic myeloid leukemia patients treated with frontline imatinib mesylate. Blood 2012;120:2794.
• 15 Uz B, Buyukasik Y, Atay H, Kelkitli E, Turgut M, Bektas O, et al. EUTOS CML prognostic scoring system predicts ELN-based 'event-free survival' better than Euro/Hasford and Sokal systems in CML patients receiving front-line imatinib mesylate. Hematology 2013;18:247-52.