title: Diagnosis and Monitoring of Chronic Myeloid Leukemia: Chiang Mai University Experience.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Chiang Mai University, Thailand E-mail : ekarat_r@hotmail.com.
authors.forename: Adisak
authors.initials: A
authors.lastname: Tantiworawit
authors.forename: Supanat
authors.initials: S
authors.lastname: Kongjarern
authors.forename: Ekarat
authors.initials: E
authors.lastname: Rattarittamrong
authors.forename: Suree
authors.initials: S
authors.lastname: Lekawanvijit
authors.forename: Kanokkan
authors.initials: K
authors.lastname: Bumroongkit
authors.forename: Nonglak
authors.initials: N
authors.lastname: Boonma
authors.forename: Thanawat
authors.initials: T
authors.lastname: Rattanathammethee
authors.forename: Sasinee
authors.initials: S
authors.lastname: Hantrakool
authors.forename: Chatree
authors.initials: C
authors.lastname: Chai-Adisaksopha
authors.forename: Lalita
authors.initials: L
authors.lastname: Norasetthada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy; D010677:Philadelphia Chromosome / Q000187:drug effects*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl