Chromosome abnormalities at onset of complete remission are associated with worse outcome in patients with acute myeloid leukemia and an abnormal karyotype at diagnosis: CALGB 8461 (Alliance)

Abstract

Achievement of complete remission is essential for long-term survival of acute myeloid leukemia patients. We evaluated the prognostic significance of cytogenetics at complete remission in 258 adults with de novo acute myeloid leukemia and abnormal pre-treatment karyotypes, treated on Cancer and Leukemia Group B front-line studies, with cytogenetic data at onset of morphological complete remission. Thirty-two patients had abnormal karyotypes at time of initial complete remission. Of these, 28 had at least 1 abnormality identified pre-treatment, and 4 acute myeloid leukemia-related abnormalities not detected pre-treatment. Two hundred and twenty-six patients had normal remission karyotypes. Patients with abnormal remission karyotypes were older (P<0.001), had lower pre-treatment white blood counts (P=0.002) and blood blast percentages (P=0.004), were less often classified as Favorable and more often as Adverse among European LeukemiaNet Genetic Groups (P<0.001), and had shorter disease-free survival (median 0.6 vs. 0.9 years; P<0.001) and overall survival (median 1.2 vs. 2.2 years; P<0.001) than patients with normal remission karyotypes. Sixteen patients with normal remission karyotypes also harbored non-clonal abnormalities unrelated to pre-treatment karyotypes. They had shorter overall survival than 210 patients with only normal metaphases (P=0.04). Forty-eight patients with any clonal or non-clonal chromosome abnormality at complete remission had worse disease-free survival (median 0.6 vs. 1.0 years; P<0.001) and overall survival (median 1.2 vs. 2.5 years; P<0.001) than 210 patients with exclusively normal metaphases. In multivariable analyses, after adjustment for age, the presence of any remission abnormality was associated with shorter disease-free survival (P=0.03) and overall survival (P=0.01). We conclude that detection of any abnormality at complete remission is an adverse prognostic factor. (clinicaltrials.gov identifier: 00048958).

Trial registration: ClinicalTrials.gov NCT00048958.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.

Overview of the study design. AML: acute myeloid leukemia; CALGB: Cancer and Leukemia Group B; CR: complete remission.

Figure 2.

Disease-free survival (A) and overall survival (B) of patients with de novo acute myeloid leukemia and abnormal pre-treatment karyotypes according to the presence or absence of chromosome abnormalities at the time of complete remission (CR). In these analyses, patients with non-clonal abnormalities unrelated to abnormalities detected at diagnosis are considered to have a normal karyotype at complete remission.

Figure 3.

Disease-free survival (A) and overall survival (B) of patients with de novo acute myeloid leukemia and abnormal pre-treatment karyotypes according to the presence or absence of any chromosome abnormality or abnormalities, both clonal and non-clonal, pre-treatment-related and pre-treatment-unrelated, at the time of complete remission (CR).