Red Cell Distribution Width-to-Albumin Ratio Is a Simple but Robust Prognostic Biomarker in Peripheral T-Cell Lymphoma

Background: Red cell distribution width (RDW) is the difference in the volume and size of erythrocytes. High RDW has been identified as a worse prognostic factor in various diseases, including sepsis, cerebrovascular accidents, and diverse cancers. More recently, RDW-to-albumin ratio (RAR) is a comprehensive biomarker combining inflammation and nutrition status that better reflects a patient's frailty. However, little is known about its prognostic relevance in peripheral T-cell lymphoma (PTCL), with only one publication focusing on RDW (Castro et al.).

Methods: This retrospective analysis included consecutive patients with newly diagnosed PTCL between 2007 and 2023 at Kameda Medical Center. Extranodal NK/T-cell lymphoma, adult T-cell leukemia/lymphoma, and ALK-positive anaplastic large cell lymphoma were excluded due to distinct prognosis and treatment strategies. The RDW coefficient of variation (RDW-CV) was assessed prior to treatment and calculated using the following formula: 1 standard deviation of mean corpuscular volume (MCV) divided by MCV, multiplied by 100. Receiver operating curve (ROC) analysis was used to determine the optimal cutoff value of RDW-CV and RAR for 2-year outcomes. Survival analyses were conducted using Kaplan-Meier curves with log-rank tests, and Cox proportional hazard models were used for univariate and multivariate analyses.

Results: In total, 115 patients were included in this analysis. The median age was 74 years (range 45-93), with male predominance (60.8%). Sixty-five patients (56.5%) were initially treated with the CHOP regimen, while 29 patients (25.2%) received more intensive chemotherapy. The most common disease subtype was PTCL-not otherwise specified (49.5%), followed by angioimmunoblastic lymphoma (40.0%).

The median RDW-CV and RAR were 14.8 (range 12.2-21.5) and 4.61 (range 2.6-9.8), respectively. The RDW-CV was significantly correlated with levels of hemoglobin (R = -0.4), albumin (R = - 0.59), and lactate dehydrogenase (R = 0.27) (all P < 0.05). ROC curve analysis for 2-year survival revealed a higher area under the curve (AUC) for RAR (0.79) compared to RDW (0.74), with cutoff values of 4.4 and 14.1, respectively (Figure 1).

Using this cutoff value, patients with high RAR had significantly worse overall survival (OS) and progression free survival (PFS) than those without (2-year OS rate: 82.5% vs. 35.1%, Figure 2; 2-year PFS rate: 54.8% vs. 27.9%, P <0.001). On multivariate analysis, high RAR was associated with a significantly worse PFS (hazard ratio [HR] =1.89 [95% confidence interval 1.15-3.11], P =0.01) and OS (HR=3.02 [1.66-5.50], P <0.001) independent of the international prognostic index (IPI), dose reduction of chemotherapy and lymphoma subtype.

Conclusion: We demonstrated that RAR improved the prognostic stratification compared to RDW-CV alone. Additionally, baseline high RAR was identified as a simple but robust prognostic factor independently associated with IPI category and treatment intensity in PTCL patients.