CD4 Cell Count of More Than 250/Microl in the Peripheral Blood Is Associated with Improved Overall Survival in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Independent of the aaIPI

Background: Interaction between lymphoma and the host immune system may influence patient outcomes. The predictive value of lymphocyte subsets in the peripheral blood of patients with DLBCL on survival has not been reported. We retrospectively reviewed the flow cytometry (FCM) data of the peripheral blood in patients with DLBCL and analyzed the effect of lymphocyte subsets on overall survival from the time of FCM.

Patients and Methods: Multicolor FCM was performed on 103 patients with DLBCL treated at Fox Chase Cancer Center (during 1996–2006). All pathology specimens were centrally reviewed. About half of these patients were treated by various regimens before referral to our center. Sixty-one males and 42 females with a median age of 64 years (19–89) were studied. Absolute lymphocyte count (ALC), NK cell (CD56⁺CD3⁻), CD3⁺CD4⁺ T cell and CD3⁺CD8⁺ T cell subsets were calculated. Median overall survival (OS) from time of FCM in all evaluable patients (91) was 22 months (range: 3 to 126 months). Median cell counts were as follows: NK cells 140, CD4⁺= 355, CD8⁺=224 and the ALC= 1064. Univariate analysis was done via Kaplan-Meier estimation and multivariate analysis via Cox proportional hazard model.

Results: We found, in univariate analysis, that OS from the date of initial FCM was significantly correlated with increased CD4⁺ T cell count and ALC, with cutoffs of 250 and 1000 cells/microL, respectively. No significant cut-off was found for CD56⁺ or CD8⁺ cells. The hazard ratio for OS by CD4⁺ T cell-count is 0.240 (95% CI 0.099–0.581; p = 0.0015) and for ALC is 0.44 (95% CI: 0.217–0.905; p = 0.0256). In multivariate analysis, for patients with either lower risk aaIPI (0–1) or higher risk (2–3), the only significant predictor of OS, based on FCM data, is the CD4⁺ T cell-count (p =0.0098 hazard ratio 0.251, 95% CI 0.0088 to 0.716).

Conclusion: In patients with diffuse large B-cell lymphoma referred for management at a tertiary cancer center regardless of prior therapy, CD4⁺ T cell levels of more than 250/microl predict improved overall survival independent of the IPI.