Although cancer is one of the major health problems worldwide, unlike adults, it is rare in childhood. In children, while cancer is the second most common cause of death in developed countries, it ranks fourth in developing countries. The improvement in overall survival rates in the last three to four decades is satisfactory. In this population, the main factors affecting overall survival rates are pathological diagnosis, stage (in some cancers, localized, locoregional, or metastatic), and age at diagnosis (
2). There are also prognostic factors specific to the type of cancers in children. Especially in adult cancers, the inflammatory biomarkers showing biological inflammatory status have been commonly used lately. Some of these inflammatory biomarkers are SIRI, SII index, NLR, PLR, CRP-albumin ratio, and HALP score (
5-
9). There is little experience with the use of these inflammatory biological markers in childhood (
10-
12). Herein, the aim of our study was to evaluate the importance of the biological inflammatory markers, including SII index, SIRI, and HALP score in children with cancer.
There are studies showing that increased leukocyte count is associated with poor prognosis in cancer patients, especially leukemia (
17,
18). The studies on the importance of leukocyte count in malignant diseases other than leukemia in children are few. Logically, given that leukocyte counts increase in inflammation, higher leukocyte counts in cancer patients than in healthy controls can be expected. The prognostic significance of the leukocyte count has long been known (
19,
20). In our patients, including all childhood cancers except leukemia and retinoblastoma, although the leukocyte count was higher than the control group, the difference was not statistically significant. However, when the leukocyte subgroups were examined, the neutrophil and monocyte counts of the patients were higher, and the lymphocyte counts were statistically lower than the control group. Especially the increase in the neutrophil count can be explained by inflammation and cytokines in cancer. Lymphopenia is expected to be seen in Hodgkin lymphoma or Langerhans cell histiocytosis. Lymphocyte count has prognostic significance, especially in Hodgkin lymphoma.
Recently, numerous studies have focused on the ratio of leukocytes subgroups. The inflammatory biological markers with prognostic values include NLR, PLR, and LMR (
12,
20-
27). In our study, we found that patients' neutrophil, monocyte, and platelet counts and NLR, PLR, and SIRI values were statistically higher than healthy volunteers, while lymphocyte and basophil counts, hemoglobin level, and LMR were low. The elevation in neutrophil and platelet counts is a reflection of the inflammatory process in cancer. The decrease in lymphocyte count is possibly associated with immunological events. Statistical differences in NLR, PLR, LMR, and SIRI are associated with changes in lymphocyte, neutrophil, and platelet counts. In cancer patients, low hemoglobin level is well known, and the reason is multifactorial. All these changes can be attributed to the body's response to cancer, similar to inflammation and wound healing (
28).
Studies on biological inflammatory markers in children have mostly been done on tumors of the CNS (
20,
24-
26). Preoperative leukocyte count, mean platelet volume, and NLR ratio values of children with tumors of the CNS were found to be higher than healthy volunteers. However, no association between these parameters and survival rates has been reported (
20). Another study compared children with medulloblastoma and pilocytic astrocytoma. While they found the lymphocyte count to be low in patients with medulloblastoma, NLR was high as a reflection of low lymphocyte count (
24). In another study, there was a correlation between tumor grade and neutrophil count and NLR. Li et al. (
26) assessed patients with medulloblastoma and found that while NLR and PLR had prognostic significance in univariate analysis, MLR had no prognostic significance. In multivariate analysis, NLR and PLR were found to have prognostic significance, as well.
These biological inflammatory markers were also studied in lymphomas (
12,
27,
29). The NLR, MLR, PLR, and red blood cell distribution width of children with lymphoma were higher than children with reactive lymphadenopathy. The authors suggested that these markers may be useful to determine which patients with lymphadenopathy should be referred to the advanced center at an early stage for biopsy (
12). In children with Hodgkin lymphoma, the presence of lymphopenia and leukocytosis adversely affect survival (
29). High NLR is a prognostic factor in both univariate and multivariate analyses in Hodgkin lymphoma (
27).
In children with solid tumors, high NLR affects both overall survival and event-free survival in univariate analysis, whereas only overall survival is affected in multivariate analysis (
22). In another study on children with sarcoma, low lymphocyte count, improvement in late lymphocyte count, high NLR and PLR in osteosarcoma, lymphocyte count, late recovery in lymphocyte count, high NLR in rhabdomyosarcoma, and lymphocyte count in Ewing sarcoma were found to have a prognostic significance (
23).
In our study, when we classified the diagnoses as lymphoma, tumors of the CNS, and solid tumors, it was found that there were differences between lymphocyte count, NLR, LMR, PLR, SII index, SIRI, and CRP values. These differences were found between lymphoma and solid tumors, except for the SII index. Regarding the SII index, the difference was observed between the tumors of the CNS and solid tumors. This observation may explain the main reason for this change, especially the low lymphocyte count in lymphomas. Additionally, it was found that patients with advanced disease had higher NLR, SIRI, CRP, and procalcitonin levels than patients with localized disease. This can be explained by the possibility of more intense inflammation in those with advanced disease. Finally, in our study, while the HALP score and procalcitonin values of the patients who died were higher than the patients who were alive, interestingly, the basophil counts were found to be lower. We could not explain the low number of basophils, and this brings to mind the question that whether it is a coincidence or not.
Considering our obtained findings, the lymphocyte count can be the main determining factor in these inflammatory biomarkers, as Vasquez et al. (
23) emphasized, which can be explained by the relationship between cancer and inflammation.
The most important limitation in our study was that we could not perform survival analyses due to the short follow-up periods. However, we think that the comparison of alive and dead patients can give an idea, albeit a little.
In conclusion, these inflammatory biomarkers, which have no extra cost and can be easily calculated from the complete blood count, can be used in clinical settings. Another point is that careful monitoring of lymphocyte counts, presence of lymphopenia according to age, and lymphopenia recovery time at the diagnosis may also be beneficial for determining the outcome of treatment.