Abstract
Tumor-infiltrating immune cells influence diffuse large B-cell lymphoma (DLBCL) outcome. Relatively little is known about the significance of peripheral blood immune cell counts (obtained by generally available flow cytometry) on DLBCL behavior
Patients and methods: 45 newly diagnosed DLBCL patients enrolled in an institutional protocol had blood pretreatment multicolor flow cytometry performed and immune cell counts recorded. The M/F ratio was 24/21, age 19-88, median 64; stage I: 11, II: 13, III: 6 and IV: 15. Thirty two had low/ intermediate International Prognostic Index (IPI) score (0-2) and 13 had 3+ IPI. One patient was HIV+. Thirty seven (82%) received immuno-chemotherapy and 8 had chemotherapy and/or irradiation.
Statistical Methods: The outcomes of the study were progression free survival (PFS) and overall survival (OS). Kaplan-Meier estimation method and Log-rank test were used in the univariate analysis. The Cox proportional hazard model was used for multivariable analysis (MVA). All analyses were done via SAS 9.2.
Results: Mean absolute CD4 cell count (ACD4C) was 450/c.mm and the median about 400. After follow up of 0.8 to 152 months (median: 73), 25 (56%) were still alive.
Univariate analysis: significant predictors to PFS were: age (HR=1.05, 95%CI: 1.02-1.09, p=0.005), ACD4C (HR= 0.998, 95% CI: 0.966-1.000, p= 0.023] and IPI (HR=0.05, 95%CI: 0.995-1.89, p= 0.054). But for OS ACD4C was only marginally significant (p= 0.083). Absolute lymphocyte count (ALC), CD8 and [CD3-C56+ (NK)] counts did not correlate with OS or PFS.
When analyzed as a binary variable with cutoff of 450/cmm, the 18 patients with high ACD4C had better 5 year PFS, 88% vs. 52% (p= 0. 023), figure (1), and OS, 88% vs. 59% (0.054) than the 27 with low ACD4C. Age, IPI groups (low /intermediate versus high) and ALC also correlated with PFS and OS, but not the CD8 or NK cell counts.
MVA with age as a continuous variable, IPI groups and ACD4C of 450/cmm; age and ACD4C only were significant for PFS, (p= 0.008 and 0.036 respectively). For OS age was the only significant variable (p=0.017). ALC, CD8 and NK cell counts did not correlate with PFS or OS.
Conclusion: Though the series contains more early stage patients than usual, blood ACD4C seems to be a predictor of PFS and to a lesser extent OS in DLBCL independent of age and IPI. If confirmed in a larger prospective study of uniformly treated patients ACD4C may serve as an immunological marker for DLBCL biological behavior.
Progression Free Survival
No relevant conflicts of interest to declare.
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