Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase

The development of chromosomal abnormalities (CAs) in the Philadelphia chromosome (Ph)-negative metaphases during imatinib (IM) therapy in patients with newly diagnosed chronic myecloid leukemia (CML) has been reported only anecdotally. We assessed the frequency and significance of this phenomenon among 258 patients with newly diagnosed CML in chronic phase receiving IM. After a median follow-up of 37 months, 21 (9%) patients developed 23 CAs in Ph-negative cells; excluding -Y, this incidence was 5%. Sixteen (70%) of all CAs were observed in 2 or more metaphases. The median time from start of IM to the appearance of CAs was 18 months. The most common CAs were -Y and +8 in 9 and 3 patients, respectively. CAs were less frequent in young patients (P = .02) and those treated with high-dose IM (P = .03). In all but 3 patients, CAs were transient and disappeared after a median of 5 months. One patient developed acute myeloid leukemia (associated with -7). At last follow-up, 3 patients died from transplantation-related complications, myocardial infarction, and progressive disease and 2 lost cytogenetic response. CAs occur in Ph-negative cells in a small percentage of patients with newly diagnosed CIVIL treated with IM. In rare instances, these could reflect the emergence of a new malignant clone.