Work

Effect of Chromosomal Lesions Detected by SNP-Array Karyotyping on Survival After Allogeneic HCT for MDS and AML

Year: 2011

Type: article

Abstract: The prognostic value of chromosomal abnormalities identified by metaphase cytogenetics (MC) in MDS/AML is well-established and has been incorporated into risk stratification schemes. High density single nucleotide polymorphism array (SNP-A) is a karyotyping tool complementary to MC that can detect previously cryptic chromosomal lesions, including acquired somatic uniparental disomy (UPD). We retrospectively analyzed SNP-A results to assess the prognostic relevance of chromosomal abnormalities detected by this method in MDS/AML patients (pts) undergoing allogeneic hematopoietic cell transplantation (HCT). 38 pts who underwent allogeneic HCT between 2004 and 2009 had pre-HCT blood or marrow samples available for SNP-A testing. Cytogenetic analysis was performed on marrow aspirate by standard metaphase karyotyping methods. We performed 250K and 6.0 SNP-A analyses and correlated the results with clinical outcomes. Median pt age at HCT was 56 years (range 20-70). The indication for HCT was either MDS (n = 25, 66%) or AML arising from MDS, and HCT was performed at a median of 5 months from diagnosis (range 3-41). Donor sources were HLA-identical related (21, 55%), unrelated (13, 34%), and cord blood (4, 11%); myeloablative busulfan-based conditioning regimens were used for 24 pts (62%) and reduced intensity fludarabine-based conditioning for the remainder. Unbalanced chromosomal lesions were detected in 45% of pts by MC and 71% by SNP-A. Acquired somatic UPD, not detectable by MC, was identified in 26% of pts. The presence of SNP-A abnormalities was associated with a trend toward worse overall survival (OS) (16 months vs 45, p = .11). The group of pts < 60 years of age displayed significantly worse OS when SNP-A abnormalities were identified (7 months vs not reached, p = .024). HCT patients with UPD exhibited worse OS (8.8 months vs not reached, p = .016) and relapse-free survival (RFS) (6.6 vs 17.6, p = .018) than those without such lesions. None of the other factors analyzed including the number of prior therapies, HCT donor source, conditioning regimen, or time from diagnosis to HCT was associated with OS or RFS in univariate analyses. We conclude that the detection of new SNP-A abnormalities, particularly UPD, may provide important prognostic information in pts with MDS/AML undergoing HCT and should be further investigated.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2010.12.286