Core binding factor (CBF) acute myeloid leukemia (AML) is a specific subgroup of AML, which is commonly related with rearrangements of genes encoding subunits of CBF, AML1 /RUNX1 (AML1-ETO) in t(8;21)(q22;q22) or CBFB (CBFB-MYH11) in inv(16)(p13q22)/t(16;16)(p13;q22), and both clinical outcomes are usually superior in de novo AML. According to literatures, the frequency of patients with t(8;21)(q22;q22) among AML is higher in Japan and Korea than Western countries. However, the accurate incidence and clinical features of CBF-AML are unclear in a large cohort.
We have analyzed 1,536 de novo AML patients from 2 clinical trials of Japan Adult Leukemia Study Group (JALSG, AML97 and AML201 studies, registered from December 1997 to December 2005) and 876 from 3 institutes in Korea (diagnosed from January 2007 to December 2011). Patients from 15 to 64 years old were included in this study, but those with FAB-M3/t(15;17)(q22;q12–21) were excluded.
The incidence of CBF-AML was similar in both Japan and Korea (23.3% and 21.2%, P=0.2), however, that of t(8;21) and inv(16) each was a little different between both countries. t(8;21) and inv(16) were observed in 18.6% and 4.9% in Japan, and in 15.0% and 6.3% in Korea, respectively. Of these, the incidence of t(8;21) in Korea was lower than that in Japan (P=0.02), but higher than those reported from Western countries [4.9–8.6% in MRC, CALGB, and SWOG/ECOG except t(15;17), P<0.001].
The prognoses of patients with t(8;21) and inv(16) were similar in complete remission (CR) rate between both countries, but different in 5-year overall survival (OS) and disease-free survival (DFS) rates. CR rate was 91.3% (Japan) and 93.9% (Korea) in t(8;21) (p=0.3), and 98.7% and 100% in inv(16) (P=0.6), respectively. In t(8;21), OS was relatively better in Japan than in Korea (64.6% versus 54.9%, P=0.055), however, DFS tended to be worse in Japan than in Korea (47.6% versus 56.1%, P=0.47). In inv(16), almost the same results with t(8;21) were observed (72.6% versus 65.7% in OS, P=0.2, and 47.7% versus 62.2% in DFS, P=0.06).
The white blood cell (WBC) counts and WBC index were prognostic factors in patients with t(8;21), and significantly related to clinical outcome in Japanese patients, however, no significant differences were observed in Korean patients. Patients with t(8;21) having high WBC count (>=10×109/L) were found to have a poor outcome in Japan (44.8% versus 74.5% in OS and 32.4% versus 57.5% in DFS; P<0.001 each), but not in Korea (53.0% versus 57.1% in OS, P=0.8, and 54.0% versus 58.2% in DFS; P=0.6).
Additional chromosome abnormalities found in t(8;21) and inv(16) were similar in both countries. In t(8;21), a sole t(8;21) was observed in 25.5% and 25.2%, a loss of a sex chromosome (-X/-Y) in 60.8% and 60.3%, del(9q) in 8.4% and 6.1%, and other abnormalities including 7q- in 23.8% and 29.0% in Japan and Korea, respectively. However, correlations of additional chromosome abnormalities and clinical outcome were different in each country. In Japan, patients with -X/-Y had relatively favorable OS than those with sole t(8;21) [69.1% versus 57.5%, P=0.08]. However, opposite correlation was observed in Korea [48.1% in -X/-Y versus 59.6% in sole t(8;21), P=0.03], although sole t(8;21) had identical OS in both counties [57.5% versus 59.6%, P=0.4]
High incidence of t(8;21) in AML was observed in both countries, however, prognostic significance of various factors, such as WBC counts, WBC index, and additional chromosome abnormalities, were different in each country. One of the reasons for these differences may be dependent on the different treatment protocols in each country, and further analysis of factors associated with prognosis in each country is needed.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.