Publications

Abstract

Background: Arginase-1 (Arg-1) is a key enzyme contained in neutrophils' granules to mediate immunosuppression in Hodgkin lymphoma (HL). Our previous work showed that Arg-1 is a potential biomarker in HL. To define its value as a marker to monitor treatment response, we correlated serial Arg levels with clinical response in newly diagnosed and relapsed classical HL patients. Material and Methods: Serum was collected from 61 (39 early stage and 21 advanced stage) newly diagnosed HL patients before, during and after treatment and from 10 refractory/relapsed patients before and after treatment with brentuximab. s-Arg-1 was determined by enzyme-linked immunosorbent assay and was related to pre-treatment SUVmax and SULpeak, as measured by quantification of 2-[18F] fluoro-2-deoxyglucose positron emission tomography (PET) images, and to treatment response. Results: Baseline s-Arg-1 correlated with stage of disease and bulky disease and weakly with SUVmax and SULpeak. s-Arg-1 was positively correlated to the absolute count of neutrophils (ANC) and Arg-1 detected in neutrophils by RT-PCR. Since neutrophilia could affect the amount of s-Arg-1, we considered the normalized value (norm-s-Arg-1) defined as s-Arg-1/ANC to explore any correlation with semiquantitative parameters of PET at diagnosis. Medians of SUVmax and SULpeak were respectively 12.1 (range 2.7-23.2) and 7.8 (range 1.6-15.1). SUVmax and SULpeak were weakly positively correlated to norm-s-Arg-1 (respectively, r = 0.32, p = 0.03, and r = 0.31, p = 0.03). Response to treatment was observed in 17 of 21 early-stage and 25 of 39 advanced stage patients. A level of 200 ng/mL s-Arg-1 resulted in 68% (95% CI 58-87) sensitivity and 61% (95% CI 42-86) specificity in predicting response status at 30 months (area under curve, 0.69, p = 0.01). Reduction in s-Arg-1 could be observed as early as after two cycles of chemotherapy in all responsive patients, while s-Arg-1 remained elevated during and after treatment in non-responsive patients. s-Arg-1 was elevated in all relapsed patients at time of relapse and remained elevated after salvage treatment in the four non-responsive patients, while it was suppressed in brentuximab responders. Conclusion: Baseline s-Arg-1 correlates with classical HL tumour burden, and serial levels correlate with response to treatment.