7. Additional structural chromosomal abnormalities have a negative prognostic effect in patients with inv(16)/t(16;16) acute myeloid leukemia (AML)

Abstract

Additional chromosomal abnormalities (ACAs) are considered as having no prognostic effect in inv(16)/t(16;16)/CBFB-MYH11 AML patients. However, many patients with ACAs cannot be cured by the standard-of-care therapy. This study included 264 inv(16)/t(16;16)/CBFB-MYH11 AML patients (M/F = 148/116; median age: 49, range 2-89 years). During a median follow-up of 34 months (range 1-190 months), 82 patients died, 169 achieved a complete remission and 13 had a partial response. Among 234 patients with abnormal karyotype, 218 had inv(16)(p13q22) and 16 had t(16;16)(p13;q22); and 110 (47%) had inv(16)/t(16;16) as the sole abnormality (Group A), 72 (30.8%) had one additional abnormality (Group B), and 52 (22.2%) had two or more abnormalities (complex karyotype, Group C). Of the additional abnormalities, +8 (n = 53) and +22 (n = 52) were most common, followed by 7q-/-7 (n = 28), +21 (n = 19 and –Y (n = 9). Structural abnormalities other than inv(16)/t(16;16) were found in 39 (16.7%) patients. Patients with ACA as a group (Groups B&C, n = 124) did not show inferior overall survival compared to Group A (median survival: 66 vs. 71 months, p = 0.5828). However, Group C showed a significantly shorter survival compared to patients in Groups A&B (n = 182) (median survival: 48 vs. 76 months, p = 0.0165). More interestingly, patients with additional structural abnormalities (n = 39) had a poorer prognosis than patients with additional numerical changes (n = 85) (median survival: 42 vs.146 months, p = 0.0123). This study shows that a complex karyotype, especially, additional structural abnormalities, predicts a poorer prognosis. Conventional chromosomal analysis of inv(16)/t(16;16)/CBFB-MYH11 AML patients appears to have value in stratifying patients with these neoplasm.