Clinic Trial And The Mechanism Of Arsenic Trioxide-Based Chemotherapy In Patients With Non-Hodgkin Lymphoma Or Multiple Myeloma

Objective To evaluate the therapeutic efficacy and side effect of arsenic trioxide (As₂O₃) -based chemotherapy in patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), to study the regulation of As₂O₃ to vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) , to explore the new therapeutic approach and the possible mechanism.Methods Eight patients with NHL or MM received arsenous acid injection (10/5mg daily for 7-14 days) combined Dexamethasone (10/30mg daily for 5-15 days), Vitamin C (2-3g daily for 7-20 days), Vincristine (1/2mg daily for 1-2 days) or not and other supporting drugs. These medica-tions were adjusted at any time according to the patients' changes of condition, biochemistry and other indexes. The samples of serum were taken from 3ml peripheral blood of the six patients before, amid, after every treatment respectively by centrifugalization and stored in low temperature. Every sample's content of VEGF and MMP-9 were assayed in duplicate with double antibody sandwich enzyme-linked immunosorbent assay.Results One of the NHL patients achieved a complete remission, three maintained stabilization and one progressed; All of the three MM patients achieved a partial remission. The total response rate is 87．5 percent (response was defined as CR, PR and NC). The major side effect associated with the regimen that occurred in all of the NHL patients was liver function damage which could recover to normal condition after stopping the use of As₂O₃ and utilizing supporting drugs, the side effects often occurred included digestive tract symptoms such as light abdominal distention, anepithymia, nausea, stomach discomfort, and light blood cells decrease with related infection complications, and the rare side effects included perioral numbness, vague pain at scapular region, etc; Three MM patients didn't occur evident side effects. The VEGF values of three B-cell NHL and one MM patients decreased 187．35pg/ml, 124．85pg/ml, 61．55pg/ml and 17．05 pg/ml, but the values of two T-cell-rich B-cell NHL patients increased 279．5pg/ml and 92．05pg/ml. The MMP-9 values of response patients (four NHL and one MM) decreased 863．5 ng/ml, 255．1ng/ml, 108．9 ng/ml, 47．75 ng/ml and 23．05 ng/ml, only the value of one NHL patient who failed to achieve a response increased 38．05 ng/ml.Conclusions Arsenic Trioxide-based chemotherapy has some therapeutic efficacy and less side effects in patients with NHL or MM. One of the mechanisms may be the decreasing content of VEGF and MMP-9 which inhibit angiogenesis. The changes of VEGF values of B-cell and T-cell-rich B cell NHL are different and the possible reasons may be the different action mechanisms involved in different type and the too few cases. The changes of MMP-9 values are relative with the therapeutic efficacy.