Title

Prognostic Significance of Monosomy 7 with and without Complex Karyotypes in Acute Myeloid Leukemia (AML): A Single Institutional Analysis

Document Type

Article

Publication Date

2017

Abstract

Background: Over the past few years, the presence of monosomies in AML has emerged as an important prognostic factor. The incidence of monosomal karyotype (MK) increases with age, from 4% in patients ≤ 30 years to 20% in those > 60 years. Studies show that autosomal monosomies such as monosomy 7 confer very poor prognosis with overall survival in the range of 0-3%. About 30% of patients with AML have unfavorable karyotype with a complete response rate of 50% and a 5-year overall survival of 10-20% when treated with conventional chemotherapy. Of these unfavorable subgroup, about half will present with a complex karyotype (CK), which is associated with a poor outcome, and 40% of those with CK will have a MK which carries an even worse prognosis. In a single institutional retrospective study, we analyzed the prognostic significance of monosomy 7 with/without complex karyotype.

Method: Cytogenetic and overall survival were analyzed in 137 patients with median age 65 (21-91). The analysis encompasses patients at Beaumont Hospital with confirmed AML treated between years 2010-2015 who had monosomy 7 with/without complex karyotype. Statistical analysis was performed by an independent investigator and overall Survival (OS) assessed by Kaplan-Meier method.

Results: Out of 137 patients studied, we identified 99 patients with cytogenetic abnormalities. Among the latter subgroup, 16 (16.2%) patients had monosomy 7 with one patient <30 years old. While 3 (18.8%) patients with monosomy 7 also had core binding factor (CBF), 10 (62.5%) patients had monosomy 7 in the presence of CK and 5 (31.2%) patients had monosomy 7 without CK. Twenty-two (22.2%) patients had CK without monosomy 7. Statistical analysis using the SAS System for Windows version 9.3 showed that monosomy 7 in the absence of CK carries a worse prognosis than in the presence of CK (5-year OS, 0% and 6.3% respectively, p<0.002) (Table 1). The 5-year OS observed in patients with CK alone was 22.3% (Table 1). Thus, the prognostic impact of structural chromosomal abnormalities is intensified when they occur in association with a MK such as monosomy 7. Based on our analysis, MK is more predictive of poor outcome than CK and possibly other individual unfavorable karyotypes associated with very poor outcome.

Conclusion: Occurrence of MK in the presence of CK is fairly common among patients diagnosed with AML and carries a worse prognosis. Although, our study represents a single institutional analysis, it concurs with recent reports on the prognostic significance of MK either alone or in combination with CK. Currently, the best chance at cure for patients with unfavorable karyotype who achieve compete response with induction therapy is allogeneic transplant. Such reports in our opinion should necessitate a more aggressive approach in terms of treatment options as well as early discussion with patients and families on the prognostic implications of these unfavorable karyotypes inorder to make more informed decisions.

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