DP130 | NEUTROPHIL EXTRACELLULAR TRAPS IN MYELOPROLIFERATIVE NEOPLASMS: IMPACT OF CYTOREDUCTIVE THERAPY

Background: Neutrophil extracellular traps (NETs) may contribute to immunothrombosis in myeloproliferative neoplasms (MPNs), an interplay between the innate immune system and coagulation. Assessing NETs as potential biomarkers may offer insight into disease pathogenesis and management. Aims: To evaluate the association between circulating H3.1 nucleosomes (a NET surrogate) and clinical features of MPN patients, and to assess the effect of cytoreductive therapies on H3.1 nucleosome levels. Methods: In this monocentric, prospective study, plasma samples were collected before and after treatment. H3.1 nucleosome levels were measured using the Nu.Q® NETs Immunoassay from 50 μL of K2EDTA plasma. Results: 42 MPN patients (50% female) were included: 9 ET (21%), 18 PV (43%), 10 PMF (24%), 5 post-PV/ET MF (12%). Median age was 57 years (range 18–77). Samples were collected at a median of 14 months post-diagnosis from untreated patients. Mutational status included JAK2V617F (81%), CALR (12%), MPL (5%), and one triple negative. JAK2VAF (n=15) had a median of 25% (range 7.4–87%). A history of thrombosis was reported in 9 (21%) patients; 4 were on anticoagulants. Splenomegaly was present in 14 (33%). Baseline H3.1 nucleosome levels differed significantly across MPN subtypes (p<.001), highest in MF compared to ET (p<.001) and PV (p<.001). No significant differences were found by mutation type (p=0.203) or history of thrombosis. Patients on antiaggregants (n=28) had significantly lower H3.1 nucleosomes (p=0.008). Positive correlations were observed between H3.1 nucleosomes and WBC (r=0.5, p=0.001), and JAK2VAF (r=0.5, p=0.026). After a median of 12 months of therapy, 26 patients (62%) showed a reduction in H3.1 nucleosome levels (median decrease 27%, p=0.058). Baseline median was 65 ng/mL (range 8.7–937) vs. 51 ng/mL (range 3–2770) post-therapy. Post-treatment, correlations with WBC (r=0.692, p<.001), JAK2VAF (r=0.72, p=0.003), neutrophils (r=0.60, p<.001), and NLR (r=0.31, p=0.048) persisted. NET reduction was observed in 10/15 on Ruxolitinib (–36%), 6/11 on Hydroxycarbamide (–35%), 4/6 on Momelotinib (–27%), and 6/10 on Pegylated-IFN (–6%). Conclusion: H3.1 nucleosome levels varied by MPN subtype and were reduced by cytoreductive therapy in 62% of patients, particularly in PV. Prior antiaggregant use was associated with lower levels. This is the first study assessing NET modulation by JAK inhibitors in matched pre/post MPN samples.