Clinical Implications of Simultaneous Occurrence of Variant Philadelphia Translocations in Chronic Myeloid Leukemia

Up to 90% of cases of chronic myeloid leukemia (CML) are myeloproliferative disorders characterized by a Philadelphia (Ph) chromosome with a classical t(9;22)(q34;q11). Of all CML patients, 5-10% show variant Philadelphia translocations (vPh) and are an area of research interest for their significance in predicting response to various therapies, including tyrosine kinase inhibitors. They are also being studied for prognosticating multi-year survival outcomes in varied patient populations, with conflicting results. We included 238 patients for conventional cytogenetic and fluorescence in situ hybridization study from January 2018 to October 2018. Patients with vPh in CML-Chronic Phase (CML-CP) were analyzed with respect to their demographic parameters, response to imatinib therapy, and survival. Out of 238 patients diagnosed with CML-CP, 8 patients (3.3%) showed vPh. The most common chromosomes involved in these translocations were 1, 2, 3, 4, 7, 11 and 12. In almost all the cases with variant Ph chromosome, the BCR-ABL rearrangement was detected by molecular methods or by fluorescence in situ hybridization (FISH). All patients were treated with imatinib as a first-line therapy. Rates of complete hematological response, complete cytogenetic response, and major molecular response were similar in all patients with classical Ph and variant Ph chromosome. Our data suggest that prognosis of CML patients with vPh in CML has no significant effect in predicting response to imatinib or in predicting survival.