Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma

Abstract

An easily accessible biomarker to predict early relapse in early-stage classical Hodgkin lymphoma (cHL) remains an unmet clinical need, and this study explored whether the C-reactive protein–albumin–lymphocyte (CALLY) index provides prognostic information in this setting. Ninety-three patients with early-stage cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine between January 2010 and November 2024 were analyzed retrospectively. The CALLY index was calculated as (albumin × lymphocyte count) / C-reactive protein, and its prognostic performance was assessed using receiver operating characteristic analysis, Kaplan–Meier analysis, and Cox regression. Incremental value was assessed using Harrell's concordance index, time-dependent area under the curve, and integrated discrimination improvement, and these indices were compared with the neutrophil-to-lymphocyte, platelet-to-lymphocyte, and lymphocyte-to-monocyte ratios, the Prognostic Nutritional Index, and the International Prognostic Score. Median follow-up was 71 months, and 19 progression-free survival events occurred. The optimal cut-off was 5.87. Five-year progression-free survival was 58.7% versus 94.2% for low versus high values (p<0.001) and 52.6% versus 82.4% within the unfavorable subgroup (p=0.023). A low index was independently associated with worse progression-free survival (hazard ratio 3.44, 95% confidence interval 1.09–10.89, p=0.036) and adding it to the favorable/unfavorable classification improved discrimination (concordance index 0.745 to 0.807; time-dependent area under the curve at 60 months 0.767 to 0.846, p=0.030). The CALLY index showed the highest concordance index among the markers examined, although it significantly exceeded only the International Prognostic Score. Overall survival did not differ. A low pre-treatment CALLY index was therefore associated with shorter progression-free survival in early-stage cHL; this hypothesis-generating finding requires external and positron-emission-tomography-adapted validation.