- Volume 17 Issue 4
DOI QR Code
Diagnosis and Monitoring of Chronic Myeloid Leukemia: Chiang Mai University Experience
- Tantiworawit, Adisak (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
- Kongjarern, Supanat (Department of Internal Medicine, Lampang Hospital) ;
- Rattarittamrong, Ekarat (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
- Lekawanvijit, Suree (Department of Pathology, Faculty of Medicine, Chiang Mai University) ;
- Bumroongkit, Kanokkan (Department of Anatomy, Faculty of Medicine, Chiang Mai University) ;
- Boonma, Nonglak (Department of Anatomy, Faculty of Medicine, Chiang Mai University) ;
- Rattanathammethee, Thanawat (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
- Hantrakool, Sasinee (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
- Chai-Adisaksopha, Chatree (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
- Norasetthada, Lalita (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University)
- Published : 2016.06.01
Background: A diagnosis of chronic myeloid leukemia (CML) is made on discovery of the presence of a Philadelphia (Ph) chromosome. The success of the treatment of this form of leukemia with tyrosine kinase inhibitor (TKI) is monitored by reduction of the Ph chromosome. Objective: To compare the role of conventional cytogenetic (CC) methods with a real time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization (FISH) for diagnosis and treatment monitoring of CML patients. The secondary outcome was to analyze the treatment responses to TKI in CML patients. Materials and Methods: This was a retrospective study of CML patients who attended the Hematology clinic at Chiang Mai University Hospital from 2005-2010. Medical records were reviewed for demographic data, risk score, treatment response and the results of CC methods, FISH and RQ-PCR. Results: One hundred and twenty three cases were included in the study, 57.7% of whom were male with a mean age of 46.9 years. Most of the patients registered as intermediate to high risk on the Sokal score. At diagnosis, 121 patients were tested using the CC method and 118 (95.9%) were identified as positive. Five patients failed to be diagnosed by CC methods but were positive for BCR-ABL1 using the FISH method. Imatinib was the first-line treatment used in 120 patients (97.6%). In most patients (108 out of 122, 88.5%), a complete cytogenetic response (CCyR) was achieved after TKI therapy and in 86 patients (70.5%) CCyR was achieved long term by the CC method. Five out of the 35 analyzed patients in which CCyR was achieved by the CC method had a positive FISH result. Out of the 76 patients in which CCyR was achieved, RQ-PCR classified patients to only CCyR in 17 patients (22.4%) with a deeper major molecular response (MMR) in 4 patients (5.3%) and complete molecular response (CMR) in 55 patients (72.4%). In the case of initial therapy, CCyR was achieved in 95 patients (79.1%) who received imatinib and in both patients who received dasatinib (100%). For the second line treatment, nilotinib were used in 30 patients and in 19 of them (63.3%) CCyR was achieved. In half of the 6 patients (50%) who received dasatinib as second line or third line treatment CCyR was also achieved. Conclusions: CML patients had a good response to TKI treatment. FISH could be useful for diagnosis in cases where CC analysis failed to detect the Ph chromosome. RQ-PCR was helpful in detecting any residual disease and determining the depth of the treatment response at levels greater than the CC methods.
Chronic myeloid leukemia;conventional cytogenetic method;FISH;Philadelphia chromosome
- Apperley JF (2015). Chronic myeloid leukemia. Lancet, 385, 1447-59. https://doi.org/10.1016/S0140-6736(13)62120-0
- Baccarani M, Cortes J, Pane F, et al (2009). Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol, 27, 6041-51. https://doi.org/10.1200/JCO.2009.25.0779
- Baccarani M, Deininger MW, Rosti G, et al (2013). European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Blood, 122, 872-84. https://doi.org/10.1182/blood-2013-05-501569
- Branford S, Fletcher L, Cross NC, et al (2008). Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood, 112, 3330-8. https://doi.org/10.1182/blood-2008-04-150680
- Branford S, Yeung DT, Parker WT, et al (2014). Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood, 124, 511-8. https://doi.org/10.1182/blood-2014-03-566323
- Fabarius A, Leitner A, Hochhaus A, et al (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, 6760-8. https://doi.org/10.1182/blood-2011-08-373902
- Giles FJ, le Coutre PD, Pinilla-Ibarz J, et al (2013). Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia, 27, 107-12. https://doi.org/10.1038/leu.2012.181
- Gratwohl A, Brand R, Apperley J, et al (2006). Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the chronic leukemia working party of the european group for blood and marrow transplantation (EBMT). Haematologica, 91, 513-21.
- Hasford J, Pfirrmann M, Hehlmann R, et al (1998). A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst, 90, 850-8. https://doi.org/10.1093/jnci/90.11.850
- Hasford J, Baccarani M, Hoffmann V, et al (2011). Predicting complete cytogenetic response and subsequent progressionfree survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood, 118, 686-92. https://doi.org/10.1182/blood-2010-12-319038
- Hehlmann R, Muller MC, Lauseker M, et al (2013). 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, 32, 415-23.
- Hughes TP, Hochhaus A, Branford S, et al (2010). Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood, 116, 3758-65. https://doi.org/10.1182/blood-2010-03-273979
- Kantarjian H, Sawyers C, Hochhaus A, et al (2002). Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med, 346, 645-52. https://doi.org/10.1056/NEJMoa011573
- Kantarjian H, Schiffer C, Jones D, et al (2008). Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood, 111, 1774-80. https://doi.org/10.1182/blood-2007-09-110189
- Kantarjian H, Shah NP, Hochhaus A, et al (2010). Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med, 362, 2260-70. https://doi.org/10.1056/NEJMoa1002315
- Mahon FX, Rea D, Guilhot J, et al (2010). Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol, 11, 1029-35. https://doi.org/10.1016/S1470-2045(10)70233-3
- Marin D, Ibrahim AR, Lucas C, et al (2012). Assessment of BCRABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol, 30, 232-8. https://doi.org/10.1200/JCO.2011.38.6565
- Nicolini FE, Turkina A, Shen ZX, et al (2012). An open-label, multicenter study of oral nilotinib in adult patient with imatinib-resistant or imatinib-intolerance Philadelphia chromosome positive chronic myeloid leukemia in the chronic phase, Expanding Nilotinib Access in Clinical Trial, ENACT. Cancer, 118, 118-26. https://doi.org/10.1002/cncr.26249
- O'Brien SG, Guihot F, Larson RA, et al (2003). Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med, 348, 994-1004. https://doi.org/10.1056/NEJMoa022457
- O'Brien SG, Guilhot F, Goldman J, et al (2008). International randomized study of interferon versus STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM). Blood, 112, 76.
- Payandeh M, Sadeghi M, Sadeghi E (2015). Treatment and survival in patients with chronic myeloid leukemia in a chronic phase in the West of Iran. Asian Pac J Cancer Prev, 16, 7555-9. https://doi.org/10.7314/APJCP.2015.16.17.7555
- Saglio G, Kim DW, Issaragrisil S, et al (2010). Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med, 362, 2251-9. https://doi.org/10.1056/NEJMoa0912614
- Shah NP, Guilhot F,Cortes JE, et al (2014). Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood, 123, 2317-24. https://doi.org/10.1182/blood-2013-10-532341
- Sokal JE, Cox EB, Baccarani M, et al (1984). Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood, 63, 789-99.
- Testoni N, Marzocchi G, Luatti S, et al (2009). Chronic myeloid leukemia: a prospective comparison of interphase fluorescence in situ hybridization and chromosome banding analysis for the definition of complete cytogenetic response: a study of the GIMEMA CML WP. Blood, 114, 4939-43. https://doi.org/10.1182/blood-2009-07-229864
- Vardiman JW, Melo JV, Baccarani M, et al (2008). Chronic myelogenous leukemia BCR-ABL1 positive. In: 'WHO classification of tumors of hematopoietic and lymphoid tissues', Eds Swerdlow SH, Campo E, Harris NL, et al. IARC, Lyon, 32-7.
- Wang J, Shen ZX, Saglio G, et al (2015). Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood, 125, 2771-8. https://doi.org/10.1182/blood-2014-09-601674
- Yeung DT, Osborn MP, White DL, et al (2015). TIDEL-II: firstline use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets. Blood, 125, 915-23. https://doi.org/10.1182/blood-2014-07-590315
- Droplet digital PCR for BCR/ABL(P210) detection of chronic myeloid leukemia: A high sensitive method of the minimal residual disease and disease progression vol.101, pp.3, 2018, https://doi.org/10.1111/ejh.13084