Summary & Conclusion

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1 The prognostic value of angiogenesis markers in patients with non-hodgkin lymphoma. Summary & Conclusion The current study aims to asses the prognostic value of some angiogenesis markers in patients with non-hodgkin lymphoma. This study was carried out on 38 patients with non-hodgkin s lymphoma (NHL). They were selected from the Oncology Center Mansoura University. 6 patients died either before or during taking the chemotherapy. Only 32 patients completed till the fourth cycle of chemotherapy, 17 males and 15 females, with a mean of (49.8±2.1) years. NHL patients were compared to 10 age- and sexmatched healthy volunteers, who served as a control group. Histology classification was based on the World Health Organization classification of lymphomas, they were all aggressive diffuse large B cell lymphoma and one had follicular lymphoma grade III. Staging was performed according to the Ann-Arbor criteria. Prognostic scoring was performed according to the International Prognostic Index (IPI). The clinical characteristics assessed at diagnosis were B symptoms, extranodal involvement, and performance status according to ECOG scale. 1

2 Summary & Conclusion At diagnosis and after four cycles of chemotherapeutic treatment the following laboratory investigations were carried out: A- Hematological evaluation included: Blood picture (hemoglobin concentration, red blood corpuscle count, white blood corpuscle count and platelet count) and erythrocyte sedimentation rate (ESR). B- Biochemical evaluation included: 1-Hepatic assessment (serum aminotransferases (ALT, AST) enzyme activities, total bilirubin concentration, albumin concentration). 2-Renal assessment (serum creatinine concentration) 3- Estimation of serum uric acid concentration. 4-Estimation of serum Lactate Dehydrogenase (LDH) activity. 5-Estimation of serum ß 2 -microglobulin (ß 2 -M) concentration. 6-Estimation of serum concentrations of some angiogenesis markers: [Platelet-derived growth factor-bb (PDGF- 2

3 The prognostic value of angiogenesis markers in patients with non-hodgkin lymphoma. BB), Interleukin-8 (IL-8), Hepatocyte growth factor (HGF), Endoglin (CD105)]. At the end of treatment, patient s status was re-evaluated by clinical, laboratory and radiological parameters. Response was assessed and patients were divided into responders (patients achieving complete response) and non-responders (those achieving partial response, no response and progressive disease). Haemoglobin concentration, red and white blood corpuscle counts decreased significantly in NHL patients after treatment as compared to NHL patients before treatment. However, the absence of marked leucopenia and thrombocytopenia after chemotherapy may reflect the limited side effects and the safety of chemotherapeutic given doses in this study. ESR in both the first and the second hour was significantly increased in NHL patients both before and after treatment as compared to control group. No significant difference was shown between NHL patients before and after treatment as compared to each other. Serum aminotransferases (ALT, AST) activities and total bilirubin concentration were normal values. Albumin concentration 3

4 Summary & Conclusion decreased significantly in NHL patients both before and after treatment as compared to control group. Serum creatinine concentration and uric acid concentration showed normal values. Serum LDH enzyme activity didn't change according to Ann- Arbor staging system but changed according to IPI. It was significantly increased in NHL patients both before and after treatment as compared to the control group. It decreased significantly in NHL patients after treatment as compared to them before treatment. Normalization of serum LDH occurred after treatment in only patients achieving complete response. Serum ß2-M concentration didn't change according to Ann- Arbor staging system. It changed according to IPI. Serum ß2-M concentration was significantly increased in NHL patients both before and after treatment as compared to the control group. No significant difference was shown in NHL patients after treatment as compared to NHL patients before treatment. It showed no relation to the treatment response. Pretreatment serum PDGF-BB concentration in NHL patients didn't change according to Ann-Arbor stages, IPI, B symptoms and 4

5 The prognostic value of angiogenesis markers in patients with non-hodgkin lymphoma. extranodal involvement. Serum PDGF-BB concentration in NHL patients both before and after treatment showed no significant difference as compared to the control group, but it increased significantly in NHL patients after treatment as compared to NHL patients before treatment. A significant increase was seen only in non responders after treatment, while in responders the increase was not significant. Serum IL-8 concentration did not change significantly neither according to Ann-Arbor stages nor to IPI. It tended to increase with the presence of B symptoms but it didn t reach significance, but it increased significantly with extranodal involvement. Serum IL-8 concentration was significantly increased in NHL patients both before and after treatment as compared to the control group, but it showed no significant difference in NHL patients after treatment as compared to NHL patients before treatment. It showed no change with the treatment response. Pretreatment serum HGF concentration in NHL patients showed no relation with Ann-Arbor staging system, IPI and B symptoms but showed a marginal significant increase with extranodal involvement. It was significantly increased in NHL 5

6 Summary & Conclusion patients both before and after treatment as compared to the control group, then, it showed a significant decrease in NHL patients after treatment as compared to before treatment. Serum HGF showed a significant decrease in response to treatment in only responders. Significant positive correlation was observed between serum HGF and ESR in the 1 ST hr in NHL patients. High pretreatment serum CD105 concentration showed a significant relation with Ann-Arbor staging system and IPI, but not with B symptoms or extranodal involvement. Serum CD105 concentration showed no significant difference in NHL patients both before and after treatment as compared to the control group, but it showed a significant decrease in NHL patients after treatment as compared to NHL patients before treatment. A significant decrease was seen in only non responders after treatment compared to them before treatment. A significant positive correlation was seen between serum CD105 and both WBCs count and serum ß2-M concentration in NHL patients From the present study, we can conclude that: This study is considered one of the few studies analyzing PDGF-BB isoform in NHL. Within the confines of this study, PDGF-BB 6

7 The prognostic value of angiogenesis markers in patients with non-hodgkin lymphoma. is not considered to be vital in the pathogenesis of the disease. The most important finding is that chemotherapy led to elevation of serum PDGF-BB reflecting activation of angiogenesis which can be considered one of the mechanisms of conferring chemoresistance to cancer cells or identifies patients at risk to develop side effects. Hence, if this effect of chemotherapy is confirmed by future investigations which we recommend, the combined use of antiangiogenic drugs with chemotherapy might be capable of inhibiting the consecutive activation of angiogenesis, thus might augment the therapeutic effect as development of resistance to chemotherapeutic agents is a major problem in treatment of cancer. Within the confines of this study, IL-8 was found to have a probable role in the pathogenesis of NHL due to its serum level elevation. It may have a possible role in disease dissemination by its significant association with extranodal involvement, while its marginal relation to the B symptoms confirms its role as an inflammatory cytokine. Also, a possible favorable prognostic value of a high pretreatment level of IL-8 is suggested that may need further conformation. 7

8 Summary & Conclusion The pathogenic and angiogenic importance of HGF in non Hodgkin's lymphoma is confirmed in this study, providing different information from other known prognostic factors. The more important finding is its prognostic value which is affirmed by its association with treatment response suggesting that the serial determination of serum HGF levels could represent an important clinical tool in monitoring the chemotherapeutic response. The current study is one of the pioneer studies exploring the role of Endoglin in the progression of non Hodgkin's lymphoma disease, and proves its angiogenic importance in the advanced stages. Its prognostic role is also verified reflecting the tumor load and its growth and invasive potential. While chemotherapy has a suppressive effect on CD105 level, the use of antiangiogenic factors blocking CD105 angiogenic pathway may be a promising approach in the treatment of NHL. 8

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