LAUSR

Background High-resolution genome-wide SNP-arrays detect large chromosomal aberrations including copy-neutral loss of heterozygosity (CNLOH), which is not captured in conventional cytogenetics. Methods We used SNP-array genotyping data generated by the DISCOVeRY-BMT study to detect chromosomal aberrations in pre-HCT blood samples from 1,974 acute myeloid leukemia (AML) patients. Clinical data and blood samples were available through the Center for International Blood and Marrow Transplant Research. We used Cox proportional hazard model for statistical analyses. Results AML patients in this study received unrelated donor HCT between 2000-2011 at a median age of 48.2 (range=0.6-78.0) years. About 53% of the patients were males, 7.4% had therapy-related disease, and 73% were in complete remission. Chromosomal aberrations were detected in 14.4% of the patients (Figure 1). Most common aberrations in patients with advanced disease at HCT (n=536) were copy losses in chr7 (5.8%), chr5 (4.5%), CNLOH in the following: chr13 (4.7%), chr11 (3.9%), or chr17 (3.5%), and copy gain in chr8 (3.5%). Common aberrations in patients in complete remission (n=1438) were copy-loss in chr7 (1.0%), chr5 (0.7%), and CNLOH in chr9 (0.9%) or in chr17 (0.8%) (Figure 2). Among patients with normal cytogenetics at diagnosis (n=572), 27.5% received HCT in advanced disease (of them 8.3% had chr13-CNLOH). In multivariable models including commonly detected aberrations and adjusted for important factors (footnote Figure 3), chr13-CNLOH was associated with an approximately 3-fold increased risk of leukemia relapse and post-HCT mortality in patients with advanced disease (relapse: HR=2.67, 95% CI=1.67-4.26; mortality: HR=2.79, 95% CI=1.81-4.28, p Conclusion Pre-HCT CNLOH in chr13 or chr17 are associated with inferior post-HCT survival in AML; possibly as a consequence of high risk of post-HCT leukemia relapse. CNLOH in chr13 or chr17 may provide new genomic prognostic markers that guide patient risk stratification and possibly therapeutic options.