Background/Purpose: Baseline high Neutrophil- to- lymphocyte ratio (NLR) (higher than 2.95) is associated with severe progressive skin and lung disease and with reduced 5-year survival in systemic sclerosis (SSc). It is not known whether NLR changes in response to treatment. The aim of our study was to evaluate NLR changes as a biomarker for treatment response in SSc.

Methods: Progressive SSc patients who were treated with autologous hematopoietic stem cell transplantation (AHSCT), combination therapy of rituximab and mycophenolate mofetil or chimeric antigen receptor (CAR-T) therapy were recruited, along with healthy controls (HC). 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%. Event-free survival (EFS) was defined survival without persistent major organ failure (heart, lung, kidney) at 12 months.NLR, mRSS and FVC were repeatedly assessed.

Results: Fifteen patients were recruited in the AHSCT, combination therapy and HC groups and 6 in the CAR-T group. Clinical characteristics were similar, but for lower rate of women in the CAR T group (table 1). Baseline mean NLR was high ( >2.95) in all treatment arms: AHSCT, combination therapy and CAR-T, compared to HC (1.8±0.5), p< 0.001 (table 1).  CI was similar between groups, 93% (14/15) in the AHSCT, 100% (15/15) in the combination group and (100%) in the CAR-T group. EFS was similar as well, 100% (15/15) in the AHSCT group, 93% (14/15) in the combination group and 100% for the CAR T (p=NS). A similar and statistically significant decrease in mRSS values and increase in FVC% was evident after AHSCT and in combination group at each time point up to 12 months in a linear mixed model (fig. 1a-b). Despite similar clinical response and similar decrease in CRP levels (fig. 1c), NLR decreased significantly at all timepoints only after AHSCT from 4.15±1.56 to 1.8±0.4 (fig1d) and was significantly lower compared to other groups at all time points from 3 months to 12 months, in a linear mixed model, p = 0.03.  NLR correlated with mRSS and FVC only in the AHSCT group (Fig. 2a-b). After a decrease in NLR (< 2) with clinical response, NLR increased above 3 in 2 patients who had a relapse after AHSCT, one with myocarditis and renal crisis and the other with lung fibrosis.

Conclusion: High baseline NLR decreases only after AHSCT in parallel with clinical response and in correlation with mRSS and FVC. NLR may be a simple biomarker that may reflect molecular changes that occur after AHSCT but not with other therapies. Further research should evaluate NLR as a possible biomarker to define remission and diagnose a relapse after AHSCT.  

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neutrophil-to-lymphocyte-ratio-a-possible-biomarker-for-clinical-response-after-autologous-hematopoietic-stem-cell-transplantation/