Discussion
The prognostic roles of RDW and D-Dimer were explored in subjects with DLBCL. We observed that high RDW and D-Dimer were two prognostic factors related to OS and PFS among DLBCL cases. Recently, evidence has been confirmed the relationship between RDW and poor prognosis in various cancers (44, 45). Furthermore, increased RDW was associated with worse prognosis in blood malignancies such as chronic myeloid leukemia (46), chronic lymphocytic leukemia (47), NK/T lymphoma (48), multiple myeloma (49), and DLBCL (40).
Inflammation is a pivotal factor which plays a role in progression of tumor and is known as one of its prominent features (25, 50). In this study, the pooled analysis results revealed that high values of RDW were associated with poor PFS and OS. Although the main mechanism of the relationship between RDW and the prognosis of DLBCL patients has not been clearly and fully investigated, high RDW can be attributed to the disturbance in erythropoiesis and the changes in red blood cell maturation (51).
Some findings have provided evidence that there is an association between RDW and some markers such as IL-6, CRP (C - reactive protein), TNF-I and II (Tumor Necrosis Factor), TK (Thymidine Kinase), ESR (Erythrocyte Sedimentation Rate), and Ferritin which the accuracy and sensitivity in DLBCL patients are in a state of ambiguity (13). The relationship between RDW and malnutrition conditions might be explained by treatment with poor response and poor prognosis of patients who suffer from cancer (41). In addition, the disruption in iron absorption and metabolism mechanism observed in most cancers also contributes to increase the level of RDW (52), and increased RDW is considered as a turning point in the relationship between inflammation and worse prognosis of subjects who suffer from DLBCL. On the other hand, poor coagulation conditions are associated with poor prognosis and the outcomes such as VTE (venous thrombosis embolism) and DIC (disseminated intravascular coagulation).
Treatment of various cancers is associated with hypercoagulable states and according to the evidence, the changes in coagulation and fibrinolysis pathways have a great impact on cancer prognosis (19).Moreover, tumor-related degradation products such as D-Dimer as a prognostic factor of the final outcome should be used in all types of cancer (20, 26, 29). Some studies have indicated that elevated D-Dimer values as a suitable factor in solid tumor patients is associated with poor prognosis (53) and D-Dimer decreases significantly after the first chemotherapy (19). Also, it has been proved that there is an association between values of D-Dimer and tumor progression, distant metastasis, and tumor volume (54, 55). However, our pooled analysis results showed that by increasing in the D-Dimer values as a prognostic factor, we witnessed worsening OS in the DLBCL patients.
In this study, our findings determined the prognostic role of RDW and D-Dimer in DLBCL patients. Since the values of RDW and D-Dimer can be easily accessible in the patient tests at low cost, considering to these prognostic indicators would be helpful in the prognosis of DLBCL patients. However, the present study had some limitations. As a result of small number of publications on the role of D-Dimer in DLBCL patients, it was not possible to provide PFS in this study. On the other hand, the basic values for grouping the individuals based on RDW were different in the studies. Therefore, we could not be able to conduct subgroup analysis.