Clonal chromosomal abnormalities in Philadelphia-negative cells in chronic myeloid leukemia patients treated with nilotinib used in first-line therapy

Abstract

Nilotinib is an effective option for the first-line treatment of chronic myeloid leukemia (CML) patients in chronic phase (CP). In CML patients, clonal cytogenetic abnormalities (CAs) in Philadelphia-negative (Ph-) metaphases have been widely observed after treatment with imatinib, or dasatinib/nilotinib following failure with imatinib. However, such abnormalities in CML patients treated with nilotinib as the first-line therapy have not been reported. Thirteen CML CP patients with Philadelphia-positive (Ph+) cells were initially diagnosed in our hospital from December 2010 to July 2011. Patients were followed up by clinical assessment, cytogenetic analysis, and BCR-ABL transcriptional level every 3 to 6 months. Retrospective fluorescence in situ hybridization was performed on stored bone marrow specimens of patients when the cytogenetic analysis showed CAs. During nilotinib therapy, 12 (92.3 %), 5 (38.5 %), and 2 (15.4 %) patients achieved complete cytogenetic response, major molecular response, and complete molecular response at 18 months, respectively. Two patients developed CAs in Ph- cells, including trisomy 8 and monosomies 20 and 21. Monosomies 20 and 21 appeared in the same patient simultaneously. Our data confirmed that clonal CAs in Ph- cells is a general phenomenon in Ph+ CML patient treated with tyrosine kinase inhibitors (TKIs), including nilotinib. The clinical significance of these CAs that arise in Ph+ CML patient treated with TKIs and whether these CAs exist before or after treatment of TKIs are not clear.