Impact of Additional Chromosomal Aberrations Present at Diagnosis on Outcome of Adolescent and Young Adult Chronic Myeloid Leukemia Patients: A Single Center Experience

Abstract

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.

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References

  1. 1.

    Thompson PA, Kantarjian HM, Cortes JE (2015) Diagnosis and treatment of chronic myeloid leukemia in 2015. Mayo Clin Proc 90(10):1440–1454

    Article  Google Scholar 

  2. 2.

    Kang ZJ, Liu YF, Xu LZ, Long ZJ, Huang D, Yang Y, Liu B, Feng JX, Pan YJ, Yan JS, Liu Q (2016) The Philadelphia chromosome in leukemogenesis. Chin J Cancer 35:48

    Article  Google Scholar 

  3. 3.

    Hsiao HH, Liu YC, Tsai HJ, Hsu JF, Yang WC, Chang CS, Lin SF (2011) Additional chromosome abnormalities in chronic myeloid leukemia. Kaohsiung J Med Sci 27:49–54

    CAS  Article  Google Scholar 

  4. 4.

    Melo JV, Barnes DJ (2007) Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer 7(6):441–453

    CAS  Article  Google Scholar 

  5. 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):76–80

    CAS  Article  Google Scholar 

  6. 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):3609–3616

    CAS  Article  Google Scholar 

  7. 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):872–884

    CAS  Article  Google Scholar 

  8. 8.

    Bleyer A, Ferrari A, Whelan J, Barr RD (2017) Global assessment of cancer incidence and survival in adolescents and young adults. Pediatr Blood Cancer 64(9):e26497

    Article  Google Scholar 

  9. 9.

    Clarkson B, Strife A, Wisniewski D, Lambek CL, Liu C (2003) Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategies. Leukemia 17:1211–1262

    CAS  Article  Google Scholar 

  10. 10.

    Pemmaraju N, Cortes J (2014) Chronic myeloid leukemia in adolescents and young adults: patient characteristics, outcomes and review of the literature. Acta Haematol 132:298–306

    CAS  Article  Google Scholar 

  11. 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):185–192

    CAS  Article  Google Scholar 

  12. 12.

    Sakurai M, Mori T, Karigane D, Tozawa K, Matsuki E, Shimizu T, Yokoyama K, Nakajima H, Kanda Y, Okamoto S (2015) Unfavorable outcome of chronic myelogenous leukemia in adolescent and young adults treated with tyrosine kinase inhibitors. Int J Hematol 102(3):342–348

    CAS  Article  Google Scholar 

  13. 13.

    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405

    CAS  Article  Google Scholar 

  14. 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):5963–5971

    CAS  Article  Google Scholar 

  15. 15.

    Shaffer L, Slovak M, Campbell L (2009) ISCN 2009: An international system for human cytogenetic nomenclature. Karger, Basel

    Google Scholar 

  16. 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 124:5539

  17. 17.

    Chereda B, Melo JV (2016) The biology and pathogenesis of chronic myeloid leukemia. In: Hehlmann R (ed) chronic myeloid leukemia. Springer, Cham, pp 17–39

    Google Scholar 

  18. 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 93:84–90

    CAS  Article  Google Scholar 

  19. 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):761–767

    CAS  Article  Google Scholar 

  20. 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):105–109

    CAS  Article  Google Scholar 

  21. 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):4524–4526

    CAS  Article  Google Scholar 

  22. 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 128:1926

    Article  Google Scholar 

  23. 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):6760–6768

    CAS  Article  Google Scholar 

  24. 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):1981–1987

    CAS  Article  Google Scholar 

  25. 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):48–56

    CAS  Article  Google Scholar 

  26. 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):2742–2750

    CAS  Article  Google Scholar 

  27. 27.

    O’Dwyer ME, Mauro MJ, Kurilik G, Mori M, Balleisen S, Olson S, Magenis E, Capdeville R, Druker BJ (2002) The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood 100(5):1628–1633

    Article  Google Scholar 

  28. 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):451–455

    Article  Google Scholar 

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Correspondence to Amro Mohamed Sedky El-Ghammaz.

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El-Ghammaz, A.M.S., Hamza, M.T., Said, R.M. et al. Impact of Additional Chromosomal Aberrations Present at Diagnosis on Outcome of Adolescent and Young Adult Chronic Myeloid Leukemia Patients: A Single Center Experience. Indian J Hematol Blood Transfus 35, 683–691 (2019). https://doi.org/10.1007/s12288-019-01121-w

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Keywords

  • Chronic myeloid leukemia
  • Adolescents and young adults
  • Additional chromosomal aberrations at diagnosis
  • Treatment response
  • Prognosis