Clinical Study On MTA And MEA Regimen For Treatment Of Adult Refractory Or Relapsed Acute Leukemia

Objective:The therapy of acute leukemia developed rapidly. Some patients can attain long term disease free survival by chemotherapy, stem cell transplantation, and intensive therapy. But 10-20% patients can not attain complete remission after two cycles of chemotherapy, or relapse during consolidation and sustenance therapy after complete remission (CR). Now, therapy of refractory or relapsed adult acute leukemia is difficult. The mangements of refractory or relapsed acute leukemia include drug dose increased, new agents, molecular targeting agents, or hematopoietic cell transplantation, et al. The high-dose drug mostly used is Ara-c, but it does not increase the CR rate evidently. It addes side effects and mortality rate of chemotherapy correlated. Some new regimens can increase the CR rate, reduce the mortality rate of chemotherapy correlated, prolong disease free survival of refractory or relapsed acute leukemia. In these days, The regimen composed by Mitoxantrone Cytarabine and Etoposide(MEA) is applied universally. Etoposide is the inhibitor of topoisomeraseⅡ, and Topotecan is the inhibitor of topoisomeraseⅠ. It is the basic theory that this research observes curative effect and adverse response of MEA and MTA, when Topotecan substitutes Etoposide, in the treament of refractory or relapsed acute leukemia. The CR rate, side effects and mortality rate of both regimens well be observed with aims to evaluate the clinic significance of MTA.Methods:Forty-five relapsed or refractory patients were enrolled in this study. They were younger than age 70 years old, and hospitalized in Department of Hematology of the First Affiliated Hospital, Zhengzhou University from July 2008 to March 2010. Patients were prospectivly assigned into two groups:16 patients were administrated with MTA (Mitoxantrone, Cytarabine and Topotecan) regimen, and 29 patients were administrated with MEA (Mitoxantrone, Cytarabine and Etoposide) regimen.MTA regimen:MIT 10mg/d, d1～d3; Tp 2mg/d, d1～d5;Ara-C 200mg/d, d1～d7.MEA regimen:MIT 10mg/d, d1～d3; VP-16 100mg/d, d1～d5; Ara-C 200mg/d, d1～d7.If the patient achieved partial remission after one cycle of chemotherapy, one more cycle chemotherapy would be given. If the patient did not achieve remission after one cycle of chemotherapy, alternative regimen would be used. If the patient achieved complete remission, consolidation and sustenance therapy would be given.Results:Clinical response of MTA regimen:nine out of 17 patients(56.25%) achieved complete remission (CR),1 cases (6.25%) achieved partial remission (PR),6 cases (37.50%) no response, with a total response rate at 62.50%.2 cases (12.50%) died within one month of treament.Clinical response of MEA regimen:nine out of 29 patients (31.03%) achieved complete remission (CR),4 cases (13.79%) achieved partial remission (PR),16 cases (55.18%) no response, with a total response rate at 44.82%.4 cases (13.79%) died within one month of treament.The CR rate of AML patients was 77.78% in MTA regimen groups. It was higher than the CR rate of ALL patients that was 18.56%. The CR rate of AML patients was 42.10% in MEA regimen groups. It was higher than the CR rate of ALL patients (10.00%). But it was not evidently different in statistics, respectively.The CR rate of AML patients in MTA regimen groups was 77.78%, higher than that in MEA regimen groups (42.10%). The CR rate of ALL patients in MTA regimen groups (18.56%) was higher than that in MEA regimen groups (10.00%). But it is not evidently different in statistics, respectively.Side effects of MTA regimen groups:after the initiation of MTA regimen WBC reached its lowest point of below 1.0×109/L at 7.20±3.10d. The lowest point of WBC was 0.36±0.26×109/L. The duration of WBC≤1.0×109/L was 12.00±5.70d. after the initiation of MTA regimen the duration was at 22.40±6.80d when WBC≥4.0×109/L. The lowest point of Hb reached was 59.01±10.49g/L. The Hb of nine cases reached below 60g/L. PLT reached its lowest point of below 20×109/L at 6.80±1.80d after the initiation of the regimen. The lowest point of PLT was 6.43±6.67×109/L. the duration of PLT≤20×109/L was 7.40±6.80d. After the initiation of MTA regimen the duration was at 18.00±6.70d when PLT≥100×109/L.Side effects of MEA regimen groups:after the initiation of MEA regimen WBC reached its lowest point of below 1.0×109/L at 8.00±3.30d. The lowest point of WBC was 0.47±0.33×109/L. The duration of WB≤1.0×109/L was 11.8±5.0d. after the initiation of MEA regimen the duration was at 17.80±9.30d when WBC≥4.0×109/L. The lowest point of Hb reached was 54.84±12.02g/L. The Hb of twenty-five cases reached below 60g/L. PLT reached its lowest point of below 20×109/L at 7.10±3.50d after the initiation of the regimen. The lowest point of PLT was 7.48±5.70×109/L. the duration of PLT≤20×109/L was 12.70±4.50d. After the initiation of MEA regimen the duration was at 22.7±9.6d when PLT≥100×109/L.Hematologic toxcity and nonhematologic toxcity are similar on two regimens. Not Hematological toxcity is not severe, Majority of the patients are able to bear.Conclusions:1. MTA regimen is effective. 2. The CR rate and efficiency of MTA regimen for relapsed or refractory acute leukemia is better than MEA regimen.3. The CR of MTA or MEA regimen for in the treatment AML patients is better than that in the treatment ALL patients.4. Survival rate MTA regimen is better than MEA regimen. Overall survival of MTA regimen is longer than MEA regimen.5. Hematologic toxcity and nonhematologic toxcity are similar on two regimens. Not Hematological toxcity is not severe, Majority of the patients are able to bear.