52. Novel recurrent cytogenetic abnormalities predict overall survival in tetraploid/near-tetraploid MDS/AML

Introduction

Tetraploidy (4n=92 chromosomes) and near-tetraploidy (81-103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML (∼1%). Most patients are older adults with a male predominance and poor prognosis. Recurrent abnormalities associated with T/NT MDS/AML include -5/del(5q), -7/del(7q), -17/add(17p)/i(17q), -18, +8, and +21. However, other clinically-relevant abnormalities likely remain 'hidden' in long strings of cytogenetic nomenclature that are difficult to discern by visual inspection. To date, no studies have had the statistical power and computational methodology to identify novel recurrent abnormalities associated with T/NT karyotypes that predict overall survival (OS).

Methods

We used Cytogenetic Pattern Sleuth (CytoGPS), a publicly-available bioinformatic tool (http://cytogps.org) that we developed, to convert ISCN karyotypes from a combined cohort of 75 T/NT MDS/AML cases from two institutions (OSU and MDACC) into a binary Loss-Gain-Fusion model, which is analyzable using computational methods.

Results

We performed univariate analyses on the clinical and karyotypic data. Age (continuous variable, p=0.032), prior treatment (p=0.011), and cohort (p=0.025) were associated with OS; age ?60 years (p=0.316), gender (p=0.916), karyotypic complexity (p=0.175), time from diagnosis to identification of the T/NT karyotype (p=0.419), and T/NT clone size (p=0.316) had no effect. Univariate analyses of the CytoGPS results demonstrated that -5, -16, -18, del(11)(p15.1p15.4), del(13)(q12.11q22.3), and +8 were associated with poorer OS (unadjusted p<0.05). Next we used the results of univariate analyses to build multivariate models of OS.

Conclusion

The best predictor of OS in T/NT MDS/AML patients is the presence of any one of six cytogenetic abnormalities: -5, -16, -18, del(11)(p15.1p15.4), del(13)(q12.11q22.3), +8.