Prognosis Influence of Additional Chromosome Abnormalities in Newly Diagnosed Acute Promyelocytic Leukemia with t(15;17)(q22;q21)

The therapeutic advancements over the last decade have dramatically improved the prognosis and decreased the mortality of acute promyelocytic leukemia (APL). Some patients still recur repeatedly, and the poor curative effect of some patients has become a challenging issue. Survival may be impacted by additional concurrent mechanisms linked to additional chromosome abnormalities (ACA) as a potential pathogenic factor. Therefore, to confirm the role of ACA, we retrospectively analyzed the characteristics and prognostic impact of ACA in a series of newly diagnosed APL patients with t(15;17)(q22;q21).

First, we assessed the characteristics of chromosomal abnormalities. Of these 268 patients, 208 (77.6%) had the t(15;17) as the only abnormality and 60 (22.4%) had the t(15;17) with ACA. Based on the number of ACA, the evaluable cohort of APL patients with t(15;17) was further divided into four groups: no ACA, one ACA, two ACA, and three or more ACA, with respective frequencies of 77.24%, 13.81%, 5.22%, and 3.73%. Trisomy 8 was the most frequently observed ACA, alone or combined with other anomalies in 23 cases (39.0%).

Second, there was no significant difference presented in main clinical characteristics and response to therapy between the groups t(15;17) with alone and t(15;17) with ACA ( p＞0.05). Similarly, no significant impact was observed in clinical features and response to therapy, such as median white blood cells, platelets, hemoglobin, and the rate of hematologic complete remission between patients with trisomy 8 and patients with other ACA ( p＞0.05).

Third, the influence of ACA on prognosis in APL patients with a median follow-up time of 47 months (range 1-89 months) was analyzed. There was still no significant difference in APL patients between the group t(15;17) alone and the group t(15;17) with ACA for the incidence of 5-year overall survival(OS) (90.8% vs. 86.8%, p=0.531) and 5-year disease-free survival (DFS) (89.7% vs. 85.8%, p=0.301). Interestingly, patients in APL with trisomy 8 had a poorer 5-year OS than those with other ACA (91.8% vs. 69.6%, p=0.033) and unaffected 5-year DFS (88.9% vs. 88.2%, p=0.919). The OS and DFS were similar between patients with 0 to 2 ACA and patients with 3 or more ACA ( p=0.294, p=0.283, respectively). Otherwise, no statistical difference was demonstrated for the incidence of OS ( p=0.515) and DFS (p=0.383) among the groups based on the number of ACA besides t(15;17).

Finally, the old patients with age ≥60 years were shown to have lower 5-year OS compared with young patients(67.9% vs. 94.0%, p ＜0.001) and unaffected 5-year DFS (94.3% vs. 87.8%, p=0.430). The association between age and ACA on the prognosis of APL was observed. Either Cox analysis of age and ACA or combined with age and trisomy 8, it was all indicated that age ≥60 years was only an adverse prognostic factor for survival ( p＜0.001, HR = 4.627, 95% CI: 2.144-9.982; p＜0.001, HR = 4.412, 95% CI: 2.037-9.553, respectively). It should be noted that OS significantly among the following groups of patients: ＜60 years without ACA, ≥60 years without ACA,＜60 years with ACA, and ≥60 years with ACA ( p＜0.001). The 5-year OS rates were 92.9%, 97.9%, 80.6%, and 52.5%. Overall, the group≥60 years with ACA had worse OS compared to the groups ≥60 years without ACA and＜60 years without ACA ( p＜0.001, p＜0.001, respectively ). The group＜60 years with ACA had lower OS compared to the group ≥60 years without ACA ( p＜0.001).

Our results suggested that trisomy 8 as the most common ACA seemed to be an adverse but not independent predictive factor in APL with t(15;17), while the ACA besides t(15;17) did not confer poor prognosis in APL. Elderly patients with ACA appeared to have worse OS.