In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. In a recent study the prognostic impact of individual ACAs was evaluated in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0.42) or overall survival (OS; P=0.51). When individual ACAs were evaluated, +der(22)t(9;22) and/or -9/9p in the absence of high hyperdiploidy (HeH) was present in 16% of patients and constituted a poor-risk ACA group. Patients with 1 or more poor-risk ACA in the absence of HeH had significantly shorter RFS (5-year RFS rate 33% versus 59%, P=0.01) and OS (5-year OS rate 24% versus 63%, P=0.003). Poor-risk ACAs were prognostic in patients who received imatinib and dasatinib but not in those who received ponatinib. By multivariate analysis, this poor-risk ACA group was independently associated with worse RFS (HR 2.03 [95% CI 1.08-3.30], P=0.03) and OS (HR 2.02 [95% CI 1.10-3.71], P=0.02). Patients with Ph+ ALL who have +der(22)t(9;22) and/or -9/9p in the absence of HeH have relatively poor outcomes when treated with chemotherapy plus a TKI.
The authors concluded that patients with Ph+ ALL who have +der(22)t(9;22) and/or −9/9p in the absence of high hyperdiploidy experience inferior outcomes compared with patients without ACAs when treated with chemotherapy plus a TKI.
http://onlinelibrary.wiley.com/doi/10.1002/ajh.24625/abstract
