Impact of Additional Chromosomal Aberrations Present at Diagnosis on Outcome of Adolescent and Young Adult Chronic Myeloid Leukemia Patients: A Single Center Experience
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Studying the influence of additional chromosomal aberrations (ACAs) present at diagnosis on the outcome of adolescent and young adult (AYA) chronic myeloid leukemia (CML) patients as it has not been addressed previously. Eighty-six AYA CML patients have been analyzed for occurrence of ACAs at diagnosis through performing bone marrow karyotyping. All patients received imatinib mesylate upon diagnosis of CML. Overall response, molecular response, survival status, progression and occurrence of events were monitored during the follow up period. There was a statistically significant difference between patients with and without ACAs regarding overall response (P = 0.049). There was insignificant difference between the two groups regarding achievement of major molecular response (MMR) (P = 0.594), MR4 (P = 0.282) and MR4.5 (P = 0.704). There was a significant difference between patients with and without ACAs regarding time to MMR (P = 0.042) and time to MR4 (P = 0.048) but not regarding time to MR4.5 (P = 0.065). There was insignificant impact of ACAs at diagnosis on overall survival (P = 0.152), progression free survival (P = 0.112), failure free survival (P = 0.114), event free survival (P = 0.194) and alternative treatment free survival (P = 0.731). The presence of ACAs at diagnosis does not signal worse prognosis in AYA CML patients but it may delay molecular response to imatinib mesylate.
KeywordsChronic myeloid leukemia Adolescents and young adults Additional chromosomal aberrations at diagnosis Treatment response Prognosis
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 5.Zaccaria A, Testoni N, Valenti AM, Luatti S, Tonelli M, Marzocchi G, Cipriani R, Baldazzi C, Giannini B, Stacchini M, Gamberini C, Castagnetti F, Rosti G, Azzena A, Cavazzini F, Cianciulli AM, Dalsass A, Donti E, Giugliano E, Gozzetti A, Grimoldi MG, Ronconi S, Santoro A, Spedicato F, Zanatta L, Baccarani M, GIMEMA Working Party on CML (2010) Chromosome abnormalities additional to the Philadelphia chromosome at the diagnosis of chronic myelogenous leukemia: pathogenetic and prognostic implications. Cancer Genet Cytogenet. 199(2):76–80CrossRefGoogle Scholar
- 6.Millot F, Dupraz C, Guilhot J, Suttorp M, Brizard F, Leblanc T, Güneş AM, Sedlacek P, De Bont E, Li CK, Kalwak K, Lausen B, Culic S, Dworzak M, Kaiserova E, De Moerloose B, Roula F, Biondi A, Baruchel A, Guilhot F (2017) Additional cytogenetic abnormalities and variant t(9;22) at the diagnosis of childhood chronic myeloid leukemia: the experience of the International Registry for Chronic Myeloid Leukemia in Children and Adolescents. Cancer 123(18):3609–3616CrossRefGoogle Scholar
- 7.Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6):872–884CrossRefGoogle Scholar
- 11.Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G, GIMEMA CML Working Party (2015) Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 26(1):185–192CrossRefGoogle Scholar
- 14.Guilhot J, Baccarani M, Clark RE, Cervantes F, Guilhot F, Hochhaus A, Kulikov S, Mayer J, Petzer AL, Rosti G, Rousselot P, Saglio G, Saussele S, Simonsson B, Steegmann JL, Zaritskey A, Hehlmann R (2012) Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet. Blood 119(25):5963–5971CrossRefGoogle Scholar
- 15.Shaffer L, Slovak M, Campbell L (2009) ISCN 2009: An international system for human cytogenetic nomenclature. Karger, BaselGoogle Scholar
- 16.Azzazi MO, Fahmy O, Mattar M, El-Ghandour A, El-Sorady M, Shehata S, El-Nahass Y, Hegab H, Ibrahim R, Magdy R, Ellithy H, Shazly M, Khaled RH, Sameir M, Elshaer M. Second report of Arab Leukemia Net (ALN) registry for chronic myeloid leukemia (CML) in the Middle East & North Africa Region (AFME) (2014) Epidemiology of CML and additional chromosomal abnormalities (ACAs) in Egypt, multicenter results. Blood 124:5539Google Scholar
- 18.Alhuraiji A, Kantarjian H, Boddu P, Ravandi F, Borthakur G, DiNardo C, Daver N, Kadia T, Pemmaraju N, Pierce S, Garcia-Manero G, Wierda W, Verstovsek S, Jabbour E, Cortes J (2018) Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. Am J Hematol 93:84–90CrossRefGoogle Scholar
- 19.Luatti S, Castagnetti F, Marzocchi G, Baldazzi C, Gugliotta G, Iacobucci I, Specchia G, Zanatta L, Rege-Cambrin G, Mancini M, Abruzzese E, Zaccaria A, Grimoldi MG, Gozzetti A, Ameli G, Capucci MA, Palka G, Bernasconi P, Palandri F, Pane F, Saglio G, Martinelli G, Rosti G, Baccarani M, Testoni N, Gruppo Italiano Malattie Ematologiche dell’ Adulto (GIMEMA) Working Party on CML (2012) Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis. Blood 120(4):761–767Google Scholar
- 20.Yamamoto E, Fujisawa S, Hagihara M, Tanaka M, Fujimaki K, Kishimoto K, Hashimoto C, Itabashi M, Ishibashi D, Nakajima Y, Tachibana T, Kawasaki R, Kuwabara H, Koharazawa H, Yamazaki E, Tomita N, Sakai R, Fujita H, Kanamori H, Ishigatsubo Y (2014) European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients. Cancer Sci 105(1):105–109CrossRefGoogle Scholar
- 21.Jabbour E, Cortes J, Nazha A, O’Brien S, Quintas-Cardama A, Pierce S, Garcia-Manero G, Kantarjian H (2012) EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience. Blood 119(19):4524–4526CrossRefGoogle Scholar
- 22.Liu B, Wang Y, Wei H, Liu K, Lin D, Zhou C, Mi Y, Wang J (2016) Impact of additional chromosomal abnormalities in Philadelphia-positive clone on prognosis of CML patients treated with tyrosine kinase inhibitors. Blood 128:1926Google Scholar
- 23.Fabarius A, Leitner A, Hochhaus A, Muller MC, Hanfstein B, Haferlach C, Gohring G, Schlegelberger B, Jotterand M, Reiter A, Jung-Munkwitz S, Proetel U, Schwaab J, Hofmann WK, Schubert J, Einsele H, Ho AD, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Lauseker M, Pfirrmann M, Hasford J, Saussele S, Hehlmann R, for the Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung (SAKK) and the German CML Study Group (2011) Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood 118(26):6760–6768Google Scholar
- 24.Kantarjian H, O’Brien S, Jabbour E, Garcia-Manero G, Quintas-Cardama A, Shan J, Rios MB, Ravandi F, Faderl S, Kadia T, Borthakur G, Huang X, Champlin R, Talpaz M, Cortes J (2012) Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 119(9):1981–1987CrossRefGoogle Scholar
- 25.Pfirrmann M, Baccarani M, Saussele S, Guilhot J, Cervantes F, Ossenkoppele G, Hoffmann VS, Castagnetti F, Hasford J, Hehlmann R, Simonsson B (2016) Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia 30(1):48–56CrossRefGoogle Scholar
- 26.Wang W, Cortes JE, Tang G, Khoury JD, Wang S, Bueso-Ramos CE, DiGiuseppe JA, Chen Z, Kantarjian HM, Medeiros LJ, Hu S (2016) Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood 127(22):2742–2750CrossRefGoogle Scholar
- 28.O’Dwyer ME, Mauro MJ, Blasdel C, Farnsworth M, Kurilik G, Hsieh YC, Mori M, Druker BJ (2004) Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood 103(2):451–455CrossRefGoogle Scholar