General AML

The prognostic significance of additional cytogenetic acquisition in AML patients in first relapse – a Japanese study

Additional Cytogenetic Abnormality (ACA) acquisition is a clonal evolution of Acute Myeloid Leukemia (AML) cells at a cytogenetic level between the time of diagnosis and first relapse. ACA has been reported to occur in 30–60% of relapsed AML patients.1 However, the clinical significance of ACA acquisition in AML patients in first relapse is not very clear.

In an article published in Hematological Oncology on 4th April 2017, Hiroaki Shimizu, Gunma University, Maebashi, Japan, and colleagues discuss results from their large scale retrospective study which investigated the predisposing factors and prognostic impact of ACA acquisition in AML patients at first relapse.2

In total, 144 AML patients (median age = 53 years) with cytogenetic abnormality data available at diagnosis and first relapse were included in this retrospective study.

The key results of the study were:
  • At first relapse, 41% (59/144) of patient acquired ACA
  • Significant independent predisposing factors for ACA acquisition included t(8;21) (Odds Ratio [OR] = 4.38, P = 0.005), complex karyotype (OR = 7.27, P = 0.015), and a duration of > 12 months of Complete Remission (CR [OR = 0.33, P = 0.007])
  • CR rate in patients with and without ACA acquisition; 20.0% vs 72.5%, P < 0.001
  • 3-year Overall Survival (OS) rates after the first relapse in patients with (n = 59) and without (n = 85) ACA acquisition; 8.5% vs 36.8%, P < 0.001

Overall, the authors suggested that ACA acquisition at first relapse “induces severe chemo-refractory” disease and poor outcomes. Additionally, ACA acquisition “should be considered as a potent prognostic factor when evaluating accurate prognosis in relapsed AML patients.”

Abstract

We retrospectively investigated 144 patients with relapsed acute myeloid leukemia (AML) to clarify predisposing factors and the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) at the first relapse. Additional cytogenetic abnormalities are recognized as clonal evolution at the cytogenetic level. Fifty-nine patients (41%) acquired ACA at the first relapse. The incidences of ACA acquisition varied depending on cytogenetic abnormalities at initial diagnosis. Multivariate analysis identified t(8;21), complex karyotype, and a duration of fewer than 12 months of complete remission as independent predisposing factors for ACA acquisition. Notably, patients with ACA acquisition showed a significantly lower second complete remission rate compared with those without ACA acquisition (20.0% vs 72.5%, respectively, P < .001). Furthermore, the 3-year overall survival rates after the first relapse were significantly different between patients with and without ACA acquisition (8.5% vs 36.8%, respectively, P < .001). This prognostic significance was confirmed with multivariate analysis. The hazard ratio of ACA acquisition was similar or higher than reported prognostic factors for relapsed AML patients. These findings suggested that clonal evolution detected with conventional cytogenetic analysis at the first relapse induces severe chemo-refractory characteristics in AML cells and should be considered as a potent prognostic factor when evaluating accurate prognosis in relapsed AML patients.

References
  1. Shimizu H. et al. Clinical Significance of Additional Cytogenetic Abnormalities (ACA) Acquired at the First Relapse in Adult Acute Myeloid Leukemia (AML) Patients. Blood. 2014; 124: 3673.
  2. Shimizu H. et al. Clonal evolution detected with conventional cytogenetic analysis is a potent prognostic factor in adult patients with relapsed AML. Hematol Oncol. 2017 Apr 4. DOI: 10.1002/hon.2393. [Epub ahead of print].