Abstract

Clonal heterogeneity is a hallmark of malignant transformation. In acute myeloid leukemia, acquired cytogenetic abnormalities are important independent predictors of initial response to therapy, remission duration, and overall survival. It remains poorly defined, however, whether the presence of multiple cytogenetically characterized clones affects outcomes in acute myeloid leukemia. The aim of this study was to assess the prognostic impact of cytogenetic clonal heterogeneity in acute myeloid leukemia. This analysis included 1403 newly diagnosed acute myeloid leukemia patients fit for intensive chemotherapy between the ages of 15 and 88 years enrolled on SWOG protocols. The presence of multiple cytogenetic clones was found in 164 (24%) patients with abnormal karyotype. The proportion of patients with clonal heterogeneity increased with age, being present in 20% of patients younger than 40 years, but in 30% of those over age 70 (p=0.03). Clonal heterogeneity was significantly more common in association with unfavorable karyotype. Clonal heterogeneity was associated with decreased response rates and inferior event-free, relapse-free and overall survival and was confirmed as an independent predictor of poor prognosis in multivariable analysis. Subgroup analysis showed that clonal heterogeneity adds prognostic information particularly in the unfavorable karyotype group. Our results confirm the negative prognostic impact of clonal heterogeneity in acute myeloid leukemia patients with abnormal karyotype. (ClinicalTrials.gov Identifiers: NCT014343329; NCT01338974; NCT00899171; NCT1059734; NCT01059734; NCT00899743; NCT0143329, NCT00023777; NCT00085709; NCT01360125; NCT00004217).

View details for DOI 10.3324/haematol.2014.117267

View details for PubMedID 25527568