Outcome of Complex Variant Philadelphia Positive Chromosome Translocations in the Era of Tyrosine Kinase Inhibitors,

It is important to prospectively identify patients with CML who might not respond to conventional tyrosine kinase inhibitory therapy. Cytogenetic variants of the Philadelphia (cvPh) chromosome can be observed in 5–8% of patients diagnosed with Chronic Myelogenous Leukemia (CML), and usually involve at least one or more chromosome other than 9 and 22. Specifically, cvPh refers to patients with (V;9;22), where “V” indicates one or more additional translocation partners. Previous data suggest that patients with cvPh may respond poorly to therapy (Gorusu et al, 2007), however, many were treated prior to routine use of imatinib, nilotinib, or dasatinib.

We conducted a retrospective review of 338 patients with CML treated at Moffitt Cancer Center to investigate the presence of cvPh and the outcome of these patients under treatment with TKI therapy.

Of 338 patients we identified 12 patients with cvPh (3.5%). Demographic data show male to female ratio of 5:7, and median age 50 (35–76). Two were in accelerated phase at the time of diagnosis, the remaining were in chronic phase. Baseline cytogenetics from time of diagnosis were not available in six patients. Median time to development of cvPh was 10 months (0–74). Two did not have clearly identified cvPh at diagnosis but both had complex karyotype. Eleven patients were treated with imatinib, among whom only one has shown a complete cytogenetic response (CCR). Two others continue on imatinib with unknown response status. Four patients were treated with dasatinib, including one in the frontline setting. No CCR's have been documented in this group, with two patients pending reevaluation. Seven patients were treated with nilotinib after failing a prior TKI, of whom only one has shown a CCR, with response evaluation pending in two patients. Two patients have undergone allogeneic stem cell transplant, with resolution of disease, including the nilotinib treated patient in CCR above. In this series of 12 patients, only three have shown resolution of variant translocation with a median followup of 45 months. All patients are alive at the last follow up.

In this retrospective review, patients with cvPh appear to have a more resistant genomic type, and seems to be a bad prognostic factor for response to TKI therapy.

No relevant conflicts of interest to declare.