| Objective: The treatment of relapsed leukemia is a difficulty because its complete remission (CR) rate by chemotherapy is low, with a poor therapeutic efficacy and a high mortality. Nowadays it is thought that one of the characters of tumors (including leukemia) is the capacity of infinite reduplication of the tissue, which is based on the gain of cell-immortalization. Research indicates that it is telomerase-activated that make it necessary to gain the cell- immortalization, which is the key step to cancerate cell. The domestic and abroad research indicates that telomerase activity in leukemia cell group and in acute leukemia patients' bone marrow is completely different from that in healthy people's bone marrow. Besides, the activity of telomerase falls down clearly after chemotherapy so that its value is connected with the prognosis of leukemia. Multi-drug resistance is the main reason in the failure of chemotherapy. Although some resistance reversal agents have been used in clinic, their severe side-effects are leading to a limit utility. Therefore, it has become the emphasis in the therapy of leukemia to select suitable chemotherapeutic agents, lessen drugs' side-effect and improve the prognosis of relapsed leukemia. In this study, the drug sensitivity of bone marrow primary cells was researched by MTT technique, the results of which guided the personal chemotherapy program. Besides, the telomerase activity of bone marrow primary cells was studied by TRAP techniquebefore and after chemotherapy in order to find out the relationship between telomerase activity and relapsed leukemia and multi-drug resistance. All of the studies above are for the proofs on improvement of relapsed leukemia's prognosis.Materials and Methods: The bone marrow primary cells from 29 Relapsed leukemia patients were collected, the telomerase activities of which were searched before chemotherapy by TRAP technique. Also the sensitivity to 10 chemotherapeutic agents was tested by MTT technique; following was the issue of the series of personal chemotherapy programs according to the result. Finally the telomerase activity was observed once again by TRAP technique after chemotherapy.Results: 1. The rank of killing effects of 10 chemotherapeutic agents on 15 relapsed AML patients' bone marrow primaty cells is: HHR>DNR>ACR>VP-16 >VM26>MIT>Ara-C>MTX>VCR>ADM, among which only HHA is sensitive and the rest are non-sensitive. The rank of killing effects of 10 chemotherapeutic agents on 5 relapsed ALL patients' bone marrow primary cells is: DNR>VP-16> MTX>VCR>VM26>ACR>HHR>MlT>ADM>Ara-C, among which DNR and VP-16 are sensitive, and the rest are non-sensitive.2. Among 29 relapsed leukemia patients whose telomerase activities were detected by TRAP technique, 22 ones' are positive and the rest of 7 ones' are negative. 6 ones' in 9 patients younger than 40s are positive. 16 ones' in 20 older-than-40 (including 40) are positive. There were 17 ones who have finished the treatment, among whom 7 ones' bone marrow primary cells were collected after the treatment to receive the research of telomerase activities by TRAP technique. The result is that 4 ones' are positive and 3 ones' are negative; 2 changed from negative to positive, 1 changed on the contrary, and another 1 with negative result all the time. By comparison there is not significant change in the positive rates of telomerase activity before and after the treatment, also no significant change between the group younger-than-40 and older-than-40 (including 40).3. After using the personal therapeutic program there were only 2 ones reached CR, There was 1 in 2 CR patients whose immuture cell was up to 98.5% in the bone marrow after the drug holiday. Her TA before and after the treatment are negative andpositive respectively. Another one's TA is negative all the time.4 ones died due to the complication, such as infection, and 8 ones discharged because of some reasons. The percent of immature cell in 6 patients' bone marrow didn't change transparently, comparing the rest 9 ones with obvious decrease of the percent of immature cell in the bone marrow although they didn't reached CR.Conclusion: Lit is not enough to improve the effect in case of choosing only those drugs selected by the drug sensitivity of bone marrow primary cells by MTT technique. The therapeutic efficacy should be better by various observations to indicate multi-drug resistance and by resistance reversal agents correspondingly.2. Telomerase-activated is one of the characters of the relapsed leukemia, also is the obvious raise of the positive rate. Since telomerase activity is changing according to the patient's healthy situation it can indicate the prognosis of relapsed leukemia patients.3. Telomerase activity of the relapsed leukemia patients has no relationship with age.4. Among the relapsed patients types AML-M2 is on the top, which seems to be relative with that it is iV^a whose activity is the highest one among the positive rate of TA in AML, and the patients with high TA are difficult to cure.5. Telomerase high-activated is one of the reasons to arouse drug-resistance. It is effective to restrain the TA for reversing the drug-resistance and promoting the prognosis. |
