| Objective:One of the most important breakthroughs in the field of treatment in the acute leukemia is the recent advances in the treatment of acute promyelocytic leukemia. These include the application of new targeted drugs, the optimization of induction regiments, the stratification of treatment based on patient’s risk, the monitoring of minimal residual disease. As a result, the complete remission rate has been significantly improved; most patients achieved clinical cure and had long-term disease-free survival treated by ATRA and other chemotherapeutical agents. But extramedullary relapse or bone marrow relapse could be seen in10%to30%of patients in the latter part of the maintenance therapy, especially in those patients with high risk factors such as high white blood cell count in newly diagnosed cases. Therefore, the maintenance therapy of APL is the focus of the clinical practice. The maintenance therapies of APL are in the followings:ATRA and low dose chemotherapy alternatively, AS2O3and ATRA alternatively, combined chemotherapy and ATRA, AS2O3alternatively, and combination chemotherapy with ATRA,6-MP, and MTX alternatively. At present, chemotherapy, ATRA and AS2O3for maintenance therapy in APL after remission is more commonly applied. HA regimen is composed of homoharringtonine and cytarabine. MA regimen is composed of mitoxantrone and cytarabine. In this research, HA/MA regimen, alternatively with ATRA and/or AS2O3were used for the maintenance treatment of APL, with results of shorter treatment time, significantly lowered relapse rate and longer long-term survivals.MethodsOne hundred and three APL cases were enrolled in this study. They were hospitalized in Department of Hematology of the First Affiliated Hospital, Zhengzhou University from January2003to December2011. After achieved CR by induction therapy, patients received three cycles of chemotherapy for consolidation and then were divided into two groups.Study group:twenty-three cases of APL were given the following maintenance therapy first month with ATRAx28d, second month with As2o3×20d, third month with chemotherapy, alternatively every three methods. Since October2008, it was modified as first and second month with ATRA+As2O3×10d per month, third month with chemotherapy, alternatively every three methods. The agents used as follows: ATRA25mg·m-2d-1, oral; AS2O30.16mg·kg-1·d-1, intravenous infusion; HA regimen:HHT2.5～3.0mg·m-2·d-1×5d, Cytarabine(Ara-C)100mg·m-2·d-13×d intravenously; MA regimen:mitoxantrone (MIT)5～10mg·m-2·d-1×3d intravenously; Cytarabine(Ara-C)used as above.Control group:eighty cases of APL were received maintenance therapy based on the combination chemotherapy regimens and/of ATRA alternating; or ATRA+methotrexate (MTX)+6-mercaptopurine (6-MP).All relapsed patients were treated as following methods:patients with bone marrow relapse were given ATRA puls AS2O3and/or combination chemotherapy for remission induction therapy; patients with central nervous system relapse were given intrathecal administration of chemotherapy agents including methotrexate (MTX)15mg, cytarabine (Ara-C)50mg and dexamethasone5mg, every other day, until the cerebrospinal fluid turned to normal, and then followed by once a week for a month. Results:Clinical response①Study group:Six out of23(26.09%) cases reached the long-term disease free survival (DFS),14(60.87%) cases reached continuous complete remission (CCR),1case relapsed in central nervous system leukemia (CNS-L) and died of bone marrow relapse.②Control group:Thirty-four out of80(33.01%) cases reached the long-term DFS;45(43.69%) cases reached CCR;14cases (17.5%) relapsed with2cases in central nervous system leukemia (CNS-L) and12cases in bone marrow relapse;4cases were died with1case of septic shock and3cases of relapse. There were2cases who relapsed3times and3cases who relapsed2times.Mortality:①Study group:Mortality rate was4.35%(1/23).②Control group: Mortality rate was5.00%(4/80). The mortality rates between the two groups were compared, the difference was not statistically significant(P=1.000).The mortality rate at1,2and3year in study group were4.35%(1/23),0%(0/23), and0%(0/23), respectively. The mortality rate at1,2and3year in control group were1.25%(1/80),0%(0/80) and3.75(3/80), respectively. The mortality rates between the two groups were compared, the difference was not statistically significant (P value were0.927in first year and0.811in third year).The mortality rate in study group were0%(0/12) with low-risk,0%(0/9) with standard risk and50%(1/2) with high-risk. The mortality rate in control group were2.33%(1/43) in low-risk,21.43%(6/28) in standard risk and77.77%(7/9) in high-risk. The mortality rates between the two groups were compared, the difference was not statistically significant (P value were1.000in standard risk and1.000in high-risk).Relapse rates:②Study group:Total relapse rate was4.35%(1/23).②Control group:Total relapse rate was17.5%(14/80). The relapse rates between the two groups were compared, the difference was not statistically significant (P=0.215).The relapse rate of the first year in study group was4.35%(1/23), the second year0%(0/23), and the third year0%(0/23). The relapse rate of the first year in control group was5.0%(4/80), the second year15%(12/80) and the third year6.25%(5/80). The relapse rates between the two groups were compared, the difference was not statistically significant (P value were1.000,0.108and0.497, respectively)There was no case who relapsed in bone marrow relapse and1(4.34%) case who relapsed in the central nervous system relapse in the study group. There was12/80(15%) case who relapsed in bone marrow relapse and2/80(2.5%) case who relapsed in the central nervous system relapse in the control group. The relapse rates between the two groups were compared, the difference was not statistically significant (P value were0.108in bone marrow relapse and1.000in CNS-L)The relapse rate in study group was:0%(0/12) with low-risk,0%(0/9) with standard risk and50%(1/2) with high-risk. The relapse rate in control group was2.33%(1/43) with low-risk,21.43%(6/28) with standard risk and77.77%(7/9) with high-risk. The relapse rates between the two groups were compared, the difference was not statistically significant (P value were0.951,0.995, and0.491, respectively)Overall survival rates:The OS of study group at1,2,3,5year were (95.5±4.4)%,(95.5±4.4)%,(95.5±4.4)%, and (95.5±4.4)%, respectively. The OS of control group at1,2,3,5year were (98.8±1.2)%,(98.8±1.2)%,(95.5±2.6)%and (93.8±0.30)%, respectively. The OS between the two groups were compared, the difference was not statistically significant (P value were0.326,0.326,0.810and0.994, respectively)Disease-free survival rate:The DFS of study group at1,2,3,5year were (95.7±4.3)%,(95.7±4.3)%,(95.7±4.3)%and (95.7±4.3)%. The DFS of control group at1,2,3,5year were (94.9±2.5)%,(88.4±3.6)%,(80.3±4.8)%and (80.3±4.8)%, respectively. The DFS between the two groups were compared, the difference was not statistically significant (P value were0.969,0.403,0.146and0.146, respectively)The time of maintenance therapy:There were16/23cases in the study group had stopped maintenance therapy with a median maintenance therapy time at19months(14～26months). There were57/80cases in the control group had stopped maintenance therapy with a median maintenance therapy time at27months(17～66months). The maintenance therapy time between the two groups were compared, the difference was statistically significant (P=0.000)Side effects:Of all the patients in two groups, there were minor adverse reactions, including varied degree of bone marrow suppression, fever, bleeding, gastrointestinal reaction. There were no serious damage for liver and kidney function and myocardium. Patients resumed normal treatment after supportive care.Conclusions:1. Sequential maintenance treatment with ATRA, AS2O3and HA/MA regimen alternatively for acute promyelocytic leukemia is effective with tolerable side effects.2. The time of maintenance treatment with ATRA, AS2O3and HA/MA regimen alternatively for acute promyelocytic leukemia is significantly shortened as compared to other protocols. This is Helpful in relieving patients’pain pertaining to therapy and making the patients return to normal life. |
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