Clinical and Hematological Characteristics of Patients with Chronic Myeloid Leukemia under Present-Day Conditions: Results of the Russian Part of International Multi-Center Prospective EUTOS Population-Based CML Study

MYELOID TUMORS , ,

OV Lazareva1, AG Turkina1, EYu Chelysheva1, IA Tishchenko1, MA Galaiko2, OM Senderova3, VM Pepelyaeva4, SV Meresii5, AS Luchinin6, GI Milyutina7, LV Gavrilova8, LB Avdeeva9, OYu Vinogradova10, SM Kulikov1

1 Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 NA Semahko Central Clinical Hospital No. 2 under the JSC RZD, 43 Losinoostrovskaya str., Moscow, Russian Federation, 107150

3 Irkutsk Order of the Badge of Honor District Clinical Hospital, 100 Yubileinyi microdistrict, Irkutsk, Russian Federation, 664049

4 Perm Order of the Badge of Honor District Clinical Hospital, 85 Pushkina str., Perm, Russian Federation, 614990

5 Clinical Medical Unit No. 1, 68 Gagarina b-r, Perm, Russian Federation, 614077

6 Kirov District Clinical Hospital, 42 Vorovskogo str., Kirov, Russian Federation, 610027

7 District Clinical Hospital No. 1, 86 Stanke Dmitrova pr-t, Bryansk, Russian Federation, 241033

8 Republican Clinical Hospital No. 4 under the Ministry of Health of Russia, 32 Yl’yanova str., Saransk, Russian Federation, 430032

9 District Clinical Hospital, 7 Kokhanskogo str., Chita, Russian Federation, 672038

10 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Ol’ga Veniaminovna Lazareva, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-48-60; e-mail: stakhino@gmail.com

For citation: Lazareva OV, Turkina AG, Chelysheva EYu, et al. Clinical and Hematological Characteristics of Patients with Chronic Myeloid Leukemia under Present-Day Conditions: Results of the Russian Part of International Multi-Center Prospective EUTOS Population-Based CML Study. Clinical oncohematology. 2017;10(1):65–74(In Russ).

DOI: 10.21320/2500-2139-2017-10-1-65-74

ABSTRACT

Background. Much attention has been paid to molecule-genetic diagnostics of chronic myeloid leukemia (CML) and its treatment using new highly effective methods of therapy. The baseline characteristics of patients at primary CML diagnosis are hardly discussed in literature.

Aim. To provide clinical, hematological, molecular genetic and demographic characteristics of patients obtained at primary diagnosis of CML.

Patients & Methods. Characteristics of CML patients are based on data gathered by the Russian Investigational Group for CML within the international project European Treatment and Outcome Study of CML in Europe (EUTOS, the European Treatment and Outcomes Study). The study included 197 patients with newly diagnosed CML in 6 regions of the Russian Federation (Mordovia, Kirov, Perm (2 sites), Bryansk, Irkutsk, and Chita) over the period from 2009 till 2012.

Results. The study demonstrated that 94 % of CML cases were diagnosed in the chronic phase (CP) and 6 % of cases in the acceleration phase (AP) and the blast crisis phase (BC). In 40 % of patients there were no clinical symptoms, and CML was suspected only due to changes in the CBC test. Fatigue was the main subjective complaint presented by 77 % of patients in the CP and 100 % of patients with the AP and BC. Peripheral blood leukocytosis, left shift to immature myeloid cells and increased granulocytic lineage in bone marrow were typical for the patients. In all patients, the CML diagnosis was confirmed by cytogenetic or molecular tests. The social and demographic characteristics of CML patients and comorbidities at diagnosis were analyzed.

Conclusion. Based on the results of the study, a modern «portrait of a CML patient» was obtained. The study demonstrated that cytogenetic and molecular methods allow to diagnose CML in most patients at early stages of the disease in the absence of clinical signs of progression. The data on comorbidities require a special attention while choosing a therapy considering its duration. Demographic and social characteristics of CML patients demonstrate that they are socially active, particularly interested in retaining the working capacity and quality of life.

Keywords: chronic myeloid leukemia, clinical and hematological characteristics, population-based study.

Received: August 2, 2016

Accepted: December 7, 2016

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REFERENCES

  1. Hehlmann R, Hochhaus A, Baccarani M, on behalf of the European Leukemia Net. Chronic myeloid leukemia. Lancet. 2007;370(9584):342–50. doi: 10.1016/s0140-6736(07)61165-9.
  2. Волкова М.А. Амбулаторное лечение и диспансеризация больных хроническими лейкозами. М.: Медицина, 1979. 216 с.
    [Volkova MA. Ambulatornoe lechenie i dispanserizatsiya bol’nykh khronicheskimi leikozami. (Outpatient treatment and mass health examination of patients with chronic leukemias.) Moscow: Meditsina Publ.; 1979. 216 p. (In Russ)]
  3. Туркина А.Г., Челышева Е.Ю. Стратегия терапии хронического миелолейкоза: возможности и перспективы. Терапевтический архив. 2013;7:4–9.
    [Turkina AG, Chelysheva EYu. Therapeutic strategies for chronic myeloid leukemia: possibilities and perspectives. Terapevticheskii arkhiv. 2013;7:4–9. (In Russ)]
  4. Bjorkholm M, Ohm L, Eloranta S, et al. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol. 2011;29(18):2514–20. doi: 10.1200/jco.2011.34.7146.
  5. Kantarjian H, O’Brien S, Jabbour E, et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood. 2012;119(9):1981–7. doi: 10.1182/blood-2011-08-358135.
  6. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84. doi: 10.1182/blood-2013-05-501569.
  7. Зарицкий А.Ю., Ломаиа Э.Г., Виноградова О.Ю. и др. Результаты многоцентрового исследования терапии гливеком больных хроническим миелолейкозом в хронической фазе. Гематология и трансфузиология. 2007;2:13–7.
    [Zaritskii AYu, Lomaia EG, Vinogradova OYu, et al. Results of a multi-center study of treatment of patients with chronic phase chronic myeloid leukemia with glivec. Gematologiya i transfuziologiya. 2007;2:13–7. (In Russ)]
  8. Лазарева О.В., Туркина А.Г., Гусарова Г.А. и др. Итоги 12-летней терапии ингибиторами тирозинкиназ больных в поздней хронической фазе хронического миелолейкоза после неудач лечения ИФН-a. Сибирский научный медицинский журнал. 2015;35(1):90–7.
    [Lazareva OV, Turkina AG, Gusarova GA, et al. The results of 12 years treatment of patients in late chronic phase of chronic myeloid leukemia by tyrosine kinase inhibitors after failure INF-a. Sibirskii nauchnyi meditsinskii zhurnal. 2015;35(1):90–7. (In Russ)]
  9. Шухов О.А. Молекулярная и цитогенетическая характеристика Ph-позитивного клона у больных хроническим миелолейкозом при длительном воздействии ингибиторов тирозинкиназ: Автореф. дис. ¼ канд. мед. наук. М., 2015. С. 10–11.
    [Shukhov OA. Molekulyarnaya i tsitogeneticheskaya kharakteristika Ph-pozitivnogo klona u bol’nykh khronicheskim mieloleikozom pri dlitel’nom vozdeistvii ingibitorov tirozinkinaz. (Molecular and cytogenetic characteristics of Ph-positive clone in patients with chronic myeloid leukemia after a long-term exposure to tyrokinase inhibitors.) [dissertation] Moscow; 2015. pр. 10–11. (In Russ)]
  10. O’Brien S, Abboud CN, Akhtari M, et al. Clinical Practice Guidelines in Oncology. Chronic Myelogenous Leukemia, Version 1.2014. J Natl Compr Canc Netw. 2013;11:1327–40.
  11. Воробьев А.И. (ред.). Руководство по гематологии. М.: Ньюдиамед, 2005. Т. 1. С. 251–3.
    [Vorob’ev AI, ed. Rukovodstvo po gematologii. (Guidelines on hematology.) Moscow: Newdiamed Publ.; 2005. Vol. 1. pp. 251–3. (In Russ)]
  12. Rowe JM. Clinical and laboratory features of the myeloid and lymphocytic leukemias. Am J Med Technol. 1983;49(2):103–9.
  13. Hughes TP, Goldman JM. Chronic myeloid leukemia. In: Hematology, Basic Principles and Practice, 2nd edition. Ed. by R Hoffman. New York: Churchill Livingstone; 1995. pp. 854–69.
  14. Lichtman MA. Chronic myelogenous leukemia and related disorders. In: Williams Hematology, 5th edition. Ed. by E Beutler, MA Lichtman, et al. New York: McGraw-Hill; 1995. pp. 298–324.
  15. Athens JW. Chronic Myeloid Leukemia. In: Wintrobe’s Clinical Hematology, 9th edition. Ed. by GR Lee, TC Bithell, et al. Philadelphia: Lea & Febiger; 1993. pp. 1969–98.
  16. Savage DG, Szydlo RM, Goldman JM. Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia seen at a referral center over a 16-year period. Br J Haematol. 1997;96(1):111–6. doi: 10.1046/j.1365-2141.1997.d01-1982.x.
  17. O’Brien SG, Guilhot F, Larson R, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994–1004. doi: 10.1056/nejmoa022457.
  18. Cortes JE, Baccarani M, Guilhot F, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular endpoints: tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol. 2009;28(3):424–30. doi: 10.1200/jco.2009.25.3724.
  19. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–9. doi: 10.1056/nejmoa0912614.
  20. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260–70. doi: 10.1056/nejmoa1002315.
  21. Cortes JE, Kim DW, Kantarjian HM, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol. 2012;30(28):3486–92. doi: 10.1200/jco.2011.38.7522.
  22. Castagnetti F, Testoni N, Luatti S, et al. Deletions of the derivative chromosome 9 do not influence the response and the outcome of chronic myeloid leukemia in early chronic phase treated with imatinib mesylate. GIMEMA CML Working Party analysis. J Clin Oncol. 2010;28(16):2748–54. doi: 10.1200/jco.2009.26.7963.
  23. Gugliotta G, Castagnetti F, Palandri F, et al. Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML working party. Blood. 2011;117(21):5591–9. doi: 10.1182/blood-2010-12-324228.
  24. Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus Peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010;363(26):2511–21. doi: 10.1056/nejmoa1004095.
  25. 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-ɑ in newly diagnosed chronic myeloid leukemia. J Clin Oncol. 2011;29(12):1634–42. doi: 10.1200/jco.2010.32.0598.
  26. De Lavallade H, Apperley JF, Khorashad J, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26(20):3358–63. doi: 10.1200/jco.2007.15.8154.
  27. Jain P, Kantarjian H, Nazha A, et al. Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood. 2013;121(24):4867–74. doi: 10.1182/blood-2013-03-490128.
  28. Абдулкадыров, Туркина А.Г. и др. Рекомендации по диагностике и терапии хронического миелолейкоза. СПб., М., 2013. С. 67.
    [Abdulkadyrov KM, Turkina AG, et al. Rekomendatsii po diagnostike i terapii khronicheskogo mieloleikoza. (Guidelines for diagnosis and treatment of chronic myeloid leukemia.) Saint Petersburg, Moscow; 2013. pр. 67. (In Russ)]
  29. European Leukemia Net. [Internet] Available from: http://www.leukemia-net.org/content/international_trials/structure/index_eng.html. (accessed 05.01.2017).
  30. 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(3):686–92. doi: 10.1182/blood-2010-12-319038.
  31. Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in «good-risk» chronic granulocytic leukemia. Blood. 1984;63(4):789–99.
  32. Hasford J, Pfirmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst. 1998;90(11):850–8. doi: 10.1093/jnci/90.11.850.
  33. Куликов С.М., Виноградова О.Ю., Челышева Е.Ю. и др. Заболеваемость хроническим миелолейкозом в 6 регионах России по данным популяционного исследования 2009–2012 гг. Терапевтический архив. 2014;86(7):24–30.
    [Kulikov SM, Vinogradova OYu, Chelysheva EYu, et al. Incidence of chronic myeloid leukemia in 6 regions of Russia according to the data of the 2009–2012 population-based study. Terapevticheskii arkhiv. 2014;86(7):24–30. (In Russ)]
  34. Lazareva OV, Chelysheva EYu, Tischenko IA, et al. Incidence of second neoplasm in patients with chronic myeloid leukemia analyzed in the frame of international research project EUTOS population based study in Russian Federation. EHA-20. EHA Learning Center. 2015: Abstract 103689.
  35. Deininger MWN, Druker BJ. Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib. Pharmacol Rev. 2003;55(3):401–23. doi: 10.1124/pr.55.3.4.
  36. Talpaz M, Silver RT, Druke BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928–37. doi: 10.1182/blood.v99.6.1928.
  37. Lee SJ. Chronic myeloid leukemia. Br J Haematol. 2000;111(4):993–1009. doi: 10.1111/j.1365-2141.2000.02216.x.
  38. Туркина А.Г., Голенков А.К., Напсо Л.И. и др. Российский регистр по лечению хронического миелоидного лейкоза в рутинной клинической практике: итоги многолетней работы. Эффективная фармакотерапия. 2015;10:10–5.
    [Turkina AG, Golenkov AK, Napso LI, et al. Russian Registry for treatment of chronic myeloid leukemia in routine clinical practice: results of many years of work. Effektivnaya farmakoterapiya. 2015;10:10–5. (In Russ)]
  39. 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):1336–43. doi: 10.1038/leu.2015.73.
  40. Hehlman R. How I treat CML blast crisis. Blood. 2012;120(4):737–47. doi: 10.1182/blood-2012-03-380147.
  41. Body weight index. [Internet] Available from: http://www.calculator-imt.com. (accessed 05.01.2017).