POS0849 NEUTROPHIL-TO- LYMPHOCYTE RATIO: A POSSIBLE BIOMARKER FOR CLINICAL RESPONSE AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: D. Rimar, S. Keret, L. Kaly, E. Feldman, T. Zuckerman, I. Henig, D. Yehudai Ofir, A. Shouval, A. Awisat, I. Rosner, M. Rosenbaum, N. Boulman, G. Slobodin
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Autologous hematopoietic stem cell transplantation (AHSCT) is a grade A therapy for early diffuse progressive systemic sclerosis (SSc), that has been validated in three randomized controlled trials (RCTs) compared to cyclophosphamide. We have recently shown that combination therapy with rituximab and mycophenolate mofetil (MMF) for severe progressive systemic sclerosis may result in comparable outcomes compared to AHSCT after 2 years [1]. High Neutrophil- to- lymphocyte ratio (NLR) in peripheral blood (higher than 2.95) has been found to be associated with severe progressive skin and lung disease and with reduced 5-year survival in SSc [2]. AHSCT has been shown to result in a decline in the neutrophil transcript modules correlated with an increase in FVC% and with neutrophil count. It is unknown whether NLR changes can serve as biomarker for the response to various treatments. <h3>Objectives:</h3> To evaluate NLR changes in different time points up to 2 years follow up in severe progressive SSc patients fulfilling eligibility criteria for AHSCT studies, who were treated by AHSCT, compared to similar patients who were treated with upfront combination therapy of MMF and rituximab. <h3>Methods:</h3> SSc patients in our cohort, fulfilling eligibility criteria for AHSCT, who were treated with combination therapy of rituximab and MMF (combination group) or AHSCT (AHSCT group) due to their personal preferences, were recruited. Repeated longitudinal assessment of NLR and clinical outcomes at baseline and every 6 months thereafter, for 24 months, were compared between groups using a linear mixed model. Clinical improvement (CI) at 12 months was defined as a decrease in modified Rodnan Skin Score (mRSS) by more than 25% or an increase in forced vital capacity (FVC) by more than 10% [<b>1</b>]. Event-free survival (EFS) was defined as until the occurrence of death or the development of persistent major organ failure (heart, lung or kidney) [<b>1</b>]. <h3>Results:</h3> Fifteen severe progressive SSc patients in the combination group were compared to 15 in the AHSCT group. Similar clinical characteristics were observed at baseline in both groups (Table 1). The clinical outcomes were similar between groups: CI was seen in 15 (100%) of patients in the combination group, compared to 14(93%) in the AHSCT group after 12 months (p=NS). EFS was seen in 14 patients (93%) in the combination group, compared to 15 (100%) in the AHSCT group after 24 months (p=NS). In both groups, a similar statistically significant decrease in mRSS values in each time point and an increase in FVC % predicted (at 12 and 24 weeks) were noticed (Figure 1a and 1b). NLR was high (&gt;2.95) and similar at baseline in both groups 4.15±1.56 vs. 3.874±2 (p=NS). In a linear mixed model NLR decreased significantly after treatment at 6, 12, 18 and 24 months only in the AHSCT group by 2±0.47, p&lt;0.01 and remained unchanged in the combination group -0.4±0.39 (p=NS) (<b>Figure 1c</b>), despite a similar baseline and similar decrease in CRP level between the 2 groups. In the only patient in the AHSCT who did not achieve CI the NLR remained unchanged at all-time points. <h3>Conclusion:</h3> AHSCT treatment for severe progressive SSc resulted in a decrease of NLR in parallel with clinical response. A similar NLR reduction was not evident in a comparable cohort of patients who responded clinically similarly to a combination therapy of MMF and rituximab. NLR may serve as a simple biomarker for clinical response after AHSCT that may reflect a molecular change that is not evident with conventional therapy. Further studies are needed to evaluate the use of NLR also as a marker for relapse after AHSCT and its correlation with a change in RNA gene expression. <h3>REFERENCES:</h3> [1] Keret S, Henig I, Zuckerman T, et al. Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy. Rheumatology (Oxford). 2023: kead457. [2] Wareing N, Mohan V, Taherian R, et al. Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts. Arthritis Care Res (Hoboken). 2023;75(3):648-656. <b>Table 1.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>