Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461

Abstract

We investigated the relative prognostic significance of cytogenetics in 635 adult acute myeloid leukemia (AML) patients 60 years of age or older treated on front-line protocols. Classification trees and tree-structured survival analysis (TSSA) were used to identify important cytogenetic groups, and their prognostic significance was then assessed in multivariable analysis (MVA). Overall, 48.5% achieved complete remission (CR); 6.6% survived at 5 years. Complex karyotypes with at least 3 abnormalities (complex > or = 3) and a group including "rare aberrations" predicted lower CR rates (25% and 30%) versus other patients (56%). Compared with complex > or = 3, the odds of CR were significantly higher for noncomplex karyotypes without rare aberrations on MVA. Cytogenetically, complex > or = 5 predicted inferior disease-free survival on TSSA, remaining significant on MVA together with white blood cell count (WBC), sex, and age. For survival, complex > or = 5, rare aberrations, and core-binding factor (CBF) abnormalities were prognostic (P < .001), with 5-year survivals of 0%, 0%, and 19.4%, respectively, and 7.5% for remaining patients. Together with WBC, marrow blasts, sex, and age, the cytogenetic groups remained significant on MVA. In conclusion, pretreatment cytogenetics adds to other prognostic factors in older AML patients. Patients with complex > or = 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care.

Figures

Figure 1.

Number of patients in each karyotype group of older AML patients

Figure 2.

Outcome of patients 60 years of age or older according to age decade. (A) DFS. (B) OS.

Figure 3.

Classification tree for CR after pruning. Internal leaves of the classification tree are displayed as ovals. Rectangles represent terminal leaves. The numbers inside each internal and terminal leaf represent the number of patients achieving CR out of the total number of patients included in the leaf. *Proportion of patients achieving CR.

Figure 4.

DFS according to cytogenetic risk groups. (A) Final tree by TSSA after pruning. Internal leaves are shown by ovals and terminal leaves by rectangles. The numbers inside each internal and terminal leaf represent the number of patients suffering relapse or death out of the total number of patients at risk. *Proportion of patients suffering relapse or death. (B) DFS curves comparing cytogenetic risk groups identified by TSSA. (C) DFS curves comparing patients with normal karyotype with patients who have an abnormal karyotype with fewer than 5 abnormalities.

Figure 5.

OS according to cytogenetic risk groups. (A) Final tree by TSSA after pruning. Internal leaves are shown by ovals and terminal leaves by rectangles. The numbers inside each internal and terminal leaf represent the number of patients dead out of the total number of patients at risk. *Proportion dead. (B) OS curves comparing cytogenetic risk groups identified by TSSA. (C) OS curves comparing patients with normal karyotype with patients who have an abnormal karyotype with fewer than 5 abnormalities, excluding CBF AML and rare aberrations.