IntroductionChronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder induced by a chimeric gene that results from the fusion of the ABL gene on chromosome 9 with the BCR gene on chromosome 22, leading to the formation of a new leukemiaspecific fusion gene that codes for constitutionally activated protein tyrosine kinases (PTK) of different molecular weight (p210, rarely p230 or p185/190). The oncogenic PTK, which is located in the cytoplasm, is responsible of the leukemic phenotype through the constitutive activation of several downstream pathways. [1][2][3] In more than 95% of cases, the translocation between chromosome 9 and 22 is balanced and results in the formation of a small chromosome 22 that was identified originally as Philadelphia (Ph). Rare variant translocations may be masked and detected by fluorescence in situ hybridization of interphase nuclei (I-FISH). [2][3][4][5] The BCR-ABL mRNA is detected by reverse transcriptase polymerase chain reaction (PCR) and may be quantified by real-time quantitative PCR (RT-Q-PCR). [6][7][8] After the introduction of interferon-␣ and the PTK inhibitor imatinib mesylate (IM), it has become more and more important to monitor cytogenetically the response to treatment and the course of the disease. 9-13 On the basis of chromosome banding analysis (CBA) of marrow cell metaphases, the cytogenetic response (CgR) is classified as none, minimal, minor, partial, or complete according to the percentage of Ph ϩ metaphases (95%, 95%-66%, 65%-36%, 35%-1%, and none). 14 The achievement and the maintenance of a complete cytogenetic response (CCgR) are of particular importance because a CCgR is the most solid, confirmed, early surrogate marker of progression-free survival and overall survival. [11][12][13][14][15][16] The definition of CgR by CBA requires marrow cells, which cannot be always sampled, and an adequate number of banded metaphases, which cannot be always obtained. For these reasons, I-FISH is sometimes used, with increasing frequency, as a substitute for CBA, but although there is a fairly good relationship between I-FISH and CBA data, [17][18][19][20][21][22][23][24][25][26][27][28] there are no controlled and shared For personal use only. on May 12, 2018. by guest www.bloodjournal.org From definitions of CgR by I-FISH. This study was designed with the purpose of comparing CBA and I-FISH data for the definition of CCgR.
Methods
PatientsAll the patients, at least 18 years of age, were required to have a Ph ϩ and BCR-ABL ϩ CML in early chronic phase (CP). They were enrolled in 3 prospective and concurrent studies: CML/021 (ClinTrials.gov no. NCT00514488), a phase 2 trial exploring IM 800 mg daily in intermediate Sokal risk patients with CP CML; CML/022 (ClinTrials.gov no. NCT00510926), a phase 3 trial comparing IM 400 versus 800 mg daily in high Sokal risk patients with CP CML; and CML/023, an observational study of IM 400 mg daily in patients with CP CML. These studies were promoted, sponsored, and operated by the CML Working Party of GIMEMA (previous...
