Isolated trisomy is a relatively common cytogenetic abnormality in acute myeloid leukemia (AML), but with uncertain prognostic significance. We studied a large cohort of newly diagnosed de novo AML patients karyotyped on CALGB 8461 from 1984-1999, where trisomy was the sole abnormality. The common isolated trisomies (IT(C)), +8, +11, +13 and +21, comprised 90% of all sole trisomies. The outcome of 101 IT(C) patients was compared to that of 976 with normal and "poor risk" cytogenetics. The overall survival (OS) for IT(C) patients was unsatisfactory with 10% [95% confidence interval (CI), 3-17%] alive at 5 years. Repeated cycles of I/HDAC intensification did not improve outcome. However, SCT significantly improved relapse-free survival (RFS). Among IT(C) patients <60 years in first remission, only 1 of 7 receiving SCT relapsed, compared to 16 of 19 patients treated with chemotherapy only. The prognosis of IT(C) was dependent on SCT. For non-transplanted patients, the 5-year OS for IT(C) was 5% (95% CI, 0-11%), compared to 20% (95% CI, 16-23%) for 640 normal cytogenetics patients. IT(C) was an independent adverse prognostic factor for OS in non-transplanted patients. In those receiving SCT, however, the 5-year OS for IT(C) patients (69%, 95% CI, 32-100%) was not different to that of transplanted normal cytogenetics patients (60%, 95% CI, 38-81%). We conclude that in de novo adult AML patients not receiving SCT, IT(C) appears to independently predict a poor outcome that may be improved with SCT in first remission. Prospective studies are required to confirm this hypothesis.