Determination of tumor-associated macrophages (TAM) (CD68 and CD163) ratio in tumor tissues of burkitt lymphoma patients,investigation of the effect of peripheral blood absolute monocyte count, absolute lymphocyte count, lymphocyte monocyte ratio on prognosis and survival in diagnosis and remission status

Tumor microenvironment and tumor-associated macrophages play an important role in cancer development and progression. In the literature, the effects of lymphocyte-monocyte ratio and the presence of tumor-associated macrophages on prognosis have been investigated in some cancers. However, there is no study conducted on this subject in pediatric Burkitt lymphomas. In our study, 61 patients with Burkitt lymphoma who were followed up and treated at Akdeniz University Faculty of Medicine, Department of Pediatric Hematology and Oncology between 2009 and 2021 were evaluated. It was aimed to prospectively investigate the effects of clinical features, treatment results, absolute monocyte count at the time of diagnosis, monocyte percentage, absolute lymphocyte count, lymphocyte monocyte ratio, CD68 and CD163 staining rates in tumor tissue on survival rates and prognosis. The mean age at diagnosis in our study group was 8.81 ± 4.28 years, and the M/F ratio was 4.54. Of the patients, 70.4% had advanced disease, 16 (26.2%) had bone marrow involvement, 11 (18%) had CNS involvement. Of our patients included in the study, 27 (44.2%) FAB LMB 89 and 34 (55.8%) NHL BFM 95 chemotherapy protocol were applied. Eight of 61 patients (13.1%) relapsed after a median of five months during follow-up. Relapsed patients were treated with the rituximab+ICE protocol. The mean follow-up period of the patients was 69.8±63.3 months. Five-year overall survival (OS) of the patients was 84.4%±4.8%, and event free survival (EFS) was 78.1±5.4%. While the absolute monocytes count (AMC), monocytes percentage (MP), absolute lymphocyte count (ALC) and lactate dehydrogenase (LDH) values of the patients at the time of diagnosis were higher than at the time of cessation of treatment, the lymphocyte monocytes ratio (LMR) value was lower than at the time of cessation of treatment (p<0.05). Threshold values were determined by ROC analysis for the ALC and LMR values of the patients at the time of diagnosis. Four (15.3%) of the patients with low lymphocyte/monocyte ratio were at early stage, while 22 (84.6%) of the patients with low lymphocyte/monocyte ratio had advanced disease (p=0.034). The 5-year OS of patients with high LMR was 94.0±4.1%, while it was 71.6±9.1% in patients with low LMR (log rank: 0.022). Tissue blocks of 42 patients could be stained for CD68 and CD163 by immunohistochemistry. Patients were grouped as <5%, 5%-25% and >25% according to CD68 and CD163 staining rates in tumor tissue. Relapse was more common in patients with CD68 staining rate of 5-25% (3.3% vs 36.4%) (p=0.004). CNS involvement was found more frequently in patients with CD163 staining rate >25% (12.5% vs 38.9%) (p=0.047). According to the CD68 and CD163 staining rates in the tumor tissue of the patients, no difference was found between OS and EFS. Patients with low LMR had a CD68 staining rate of <5%, had a five-year EFS of 84.6±10.0, while those with a CD68 staining rate of 5%-25% had 25.0±21.7% (log rank=0.028). ). In advanced stage patients, patients with CD68 staining rate <5% had a 5-year ASD of 88.3±6.4%, while patients with a 5%-25% had an EFS of 33.3±19.2% (log rank= 0.02). In conclusion, the clinical features and treatment results of our patients with Burkitt lymphoma are similar to the literature. It has been observed that high LMR negatively affects the overall survival rate. Five-year EFS was found to be lower in the group of patients with low LMR and those with advanced disease, whose CD68 staining rate was between 5-25%. The study is important in that it was performed for the first time in the literature in pediatric patients with Burkitt's lymphoma and that it showed the effect of LMR on survival. Although the effects of CD68 and CD163 staining rates on survival have not been demonstrated, it has been observed that the high CD68 staining rate, especially in low LMR and advanced stage patients, negatively affects disease-free life. Studies with large patient groups are needed to better elucidate the effect of LMR and CD68 on prognosis in patients with Burkitt's lymphoma. Keywords: Burkitt Lymphoma, Lymphocyte-Monocyte Ratio (LMR), Tumor-Associated Macrophage (TAM), CD68 and CD163