Patients with Chronic Myeloid Leukemia with Variant Philadelphia Chromosome (Ph) Translocations Have a Similar Outcome as Those with Classic Ph When Treated with Imatinib or 2^nd Generation TKI

Background: Variant Philadelphia chromosome (Ph) translocations frequently involving 1-2 additional chromosomes besides 9 and 22 and represent 5–10% of patients (pts) with chronic myeloid leukemia (CML). The European LeukemiaNet recommendations provide a warning for patients with variant translocations, although there is limited information about their outcome after therapy with tyrosine kinase inhibitors (TKI). Our prior analysis mostly among pts who had failed prior interferon suggested that these pts had similar outcome to those with classic Ph translocations when treated with imatinib (El-Zimaity et al; Br. J Haematol 2004).

Aims: To explore the characteristics and outcome of patients with variant translocations treated with frontline imatinib or 2^nd generation TKI (dasatinib or nilotinib) after imatinib failure.

Methods: We reviewed the outcome of all pts with CML treated at our institution in 3 groups:

1. early chronic phase (CP) receiving imatinib as initial therapy, and

2. CP treated with 2nd generation TKI after Imatinib failure,

3. accelerated phase (AP) treated with 2^nd TKI after imatinib failure.

Results of pts with variant Ph were compared to those with classic Ph.

Results: Among 554 pts (278 CP frontline imatinib, 190 CP post imatinib failure, 86 AP post Imatinib failure) 33 (6%) had variant Ph (21[8%], 6[3%], 6[7%], in each of the 3 groups, respectively). Median follow up is 55 months (mo) (2 – 90), 24 (1 – 53) mo and 29 (5 – 46) mo, respectively, for the 3 groups. Results are summarized in the following tables:

Conclusion: Pts with variant Ph have a similar prognosis to those with classic Ph translocations when treated with imatinib as initial therapy or with 2^nd generation TKI after imatinib failure. The warning category for these patients may no longer be needed in the era of TKI.