Distribution of monocyte subsets and their impact on early treatment response in hodgkin lymphoma

Aim: Monocytes are divided into at least three distinct subsets, as classical, intermediate and nonclassical, which have different functional and metabolical features. The distribution pattern of peripheral blood monocyte subsets varies in different inflammatory diseases, solid organ tumors and hematological malignancies and is suggested to play an important role in disease progression. This study aimed to investigate the impact of the the distribution of monocyte subsets at diagnosis on the early treatment response in patients with Hodgkin lymphoma. Methods: The study included 29 adult patients diagnosed with Hodgkin lymphoma admitted consecutively to the Haematology Outpatient Clinics of Cerrahpasa Medical Faculty and Istanbul Medical Faculty between September 2022 - December 2023, as well as age-sex matched 38 healthy controls, who did not have any rheumatological diseases or malignancies. Complete blood counts, blood chemistry and monocyte subsets data of 25 classical Hodgkin lymphoma patients were analyzed by flow cytometry both at the time of diagnosis and during the interim positron emission scintigraphy (PET) treatment evaluation period, prospectively. The cells in the monocyte region of CD45-SS graphic were gated based on CD14 and CD16 surface markers and classified as classical (CMo - CD14++CD16-), non-classical (NCMo - CD14+CD16++) and intermediate(IMo - CD14+CD16+) monocytes. The monocyte subtype distribution data of the patients have been statistically analyzed by comparing their RECIL treatment responses of interim PET scans. Results: The study examined 25 patients, and 13 of them (%52) were in the early stage. In total, complete response (CR) was achieved in 16 patients (64%) during the interim period. While the lymphocyte/monocyte ratio (p<0.001), the percentage of IMo (p=0.007) and NCMo (p=0.006) in the patient group was found to be significantly lower compared to healthy controls; absolute monocyte count (p=0.001) and the percentage of CMo (p<0.001) was observed to be significantly higher. The total monocyte percentage in the patients showed a significant increase (p<0.001) after treatment, and this increase was led by the CD16+ phenotypic monocyte (p=0.012) side, mainly due to increased IMos (p=0.029). In the multivariate model analysis the hemoglobin value (p=0.009), platelet count (p=0.005) and the percentage of CMo (p=0.003) showed a significant-independent variable effect. The percentage of CMo (76.8% vs 84.8%, p=0.036) and CD16-/CD16+ monocyte ratio (7.5 vs 16.7, p=0.009) at the time of diagnosis were significantly lower in the patients who achieved CR during the interim period compared to the group who did not achieve CR according to the RECIL criteria. Conclusion: Our results indicate that the monocyte subset distribution, especially the percentage of CMo at diagnosis might have a prognostic value as it seems to predict the early response in patients with Hodgkin lymphoma. Large scale studies with longer follow-up are needed to identify the exact implication of these findings. Keywords: Hodgkin Lymphoma, interim PET, monocyte subsets, prognosis, RECIL