The Impact of Chromothripsis on the Clinical Outcomes of Acute Myeloid Leukemia (AML): A Meta-Analysis

Abstract

Introduction: Chromothripsis is a single genomic catastrophic event that can involve one or several chromosomes resulting in chromosomal fragmentation. Genomic instability leading to loss of chromosomes and complex karyotype is known to be associated with resistance to chemotherapy and poor prognosis in AML. While chromothripsis is associated with aggressive clinical course in various cancers, its impact on AML clinical outcomes has not been consistently conclusive. The purpose of this meta-analysis is to evaluate the pooled effect of chromothripsis on the response rates and overall survival of patients with AML. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of AML diagnosis, English language, and studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves that compared AML outcomes with and without chromothripsis. A meta-analysis using an inverse variance method with a random-effects model was conducted. Results: Two comparative studies with a total of 444 patients were included in this meta-analysis. In the presence of chromothripsis OS was adversely impacted (HR 1.78, 95%CI: 1.05-3.01, p=0.03) with a heterogeneity estimate, I2=40%. Moreover, response rates were significantly lower in AML cases with chromothripsis versus those without (19% vs. 62%, p<0.05). Conclusions: This meta-analysis confirms the adverse impact of chromothripsis on response rates and OS of patients with AML. Disclosures No relevant conflicts of interest to declare.