We prospectively quantified
VLA-4 expression in 216 patients enrolled onto COG-AAML03P1 by flow cytometry and correlated expression levels with disease characteristics and clinical outcome.
RESULTS:
VLA-4 mean fluorescence intensity (MFI) varied 35-fold (range, 30 to 1,110; median, 219.5). High
VLA-4 expression (> median MFI), compared with low expression, was associated with younger age (7.1 v 12.1 years, respectively; P < .001), lower FLT3 internal tandem duplication prevalence (4% v 21%, respectively; P < .001), and higher likelihood of extramedullary disease (16% v 5%, respectively; P = .013). In low- and high-expression groups, rates of remission (89% v 80%, respectively; P = .137) and
minimal residual disease (29% v 25%, respectively;
P = .700) were similar. Patients with low
VLA-4 expression, compared with high expression, had a higher relapse rate (RR; 44% +/- 10% v 24% +/- 9%, respectively; P = .011) and lower disease-free survival (DFS; 48% +/- 11% v 67% +/- 10%, respectively; P = .023) after 3 years. Multivariate analyses showed that low
VLA-4 expression was an independent adverse prognostic factor for DFS (hazard ratio [HR] = 1.98; P = .038) and RR (HR = 2.77; P = .009). Subgroup analyses indicated that the prognostic role of
VLA-4 expression was most prominent in patients with standard-risk AML, in whom low
VLA-4 expression was associated with inferior DFS (34% +/- 16% v 69% +/- 14% for high expression; P = .011) and higher RR (61% +/- 16% v 26% +/- 14% for high expression; P = .009). A similar trend was seen in low-risk but not high-risk patients.
CONCLUSION: