| Objective:To observe the effect and safety of different induction regimens with same total dosage of Aza(Azacitidine),with standard dosing(standard dose group)versus low dose and long course(adjusted dose group)in treatment of elderly unfit AML(acute myeloid leukemia).Methods:The regime was discussed and then to be funded before the beginning of the non-randomized control clinical study.103 elderly patients with unfit initial treatment AML(non-acute promyelocytic leukemia,non-APL)from January 2020 to June 2021were involved in this study.Aza was administered at the standard dose of 75 mg/(m~2·d)for 7 d in standard dose group(n=50),and was administered at 100 mg/d for 7-12 d in adjusted dose group(n=53).The administration days in adjusted dose group was calculated based on the total standard dose of the patient’s single course of treatment.Subgroup analyses were performed in the two groups for effect and safety of the regime of monotherapy subgroup,the combined with the BCL-2 inhibitor subgroup and the combined low-dose chemotherapy subgroup respectively.Results:1.After 2 courses of treatment,standard dose group include 28(56.0%)patients obtained overall objective remission(ORR),of 17(34.0%)patients achieved complete remission(CR),4(8.0%)patients achieved complete remission but incomplete hemocytes recovery(Cri),7(14.0%)patients achieved partial remission(PR).37(74.0%)patients can be abserved ORR in clinic after 4 courses of treatment,meanwhile,after 6 courses of treatment,38 patients(76.0%)can obtained ORR.In the adjusted dose group,a total of 35(66.0%)patients achieved ORR after 2 cycles of treatment,including21(39.6%)patients achieved CR,6(11.3%)patients got Cri,and 8(15.1%)patients obtained PR.After 4 courses,42 patients(79.2%)obtained ORR.There were 43 patients(81.1%)achieved ORR,after 6 courses of treatment.There was no significant difference between the standard dose group and the adjusted dose group(P>0.05).2.The median follow-up time was 14 months.The 1-year overall survival(OS)was49.0%in the standard dose group and 52.8%in the adjusted dose group,there seems no significant statistical difference between two groups(P>0.05).3.The numbers of patient we can observed gradeⅢorⅣmyelosuppression was28(56.0%)in the standard dose group,33(62.3%)in the adjusted dose group.There were no significant differences(P>0.05)in the number of patients who have pneumonia,hemorrhage,gradeⅡor above nausea and vomiting and serous cavity effusion between two groups(P>0.05).4.According to individual Aza or concomitant with other drugs,standard dose group and adjusted dose group were divided into single drug group and concomitant drug group.In standard dose group,there were significantly higher efficacy in concomitant drug group compared with single Aza group(P<0.05),however,the risk of gradeⅢandⅣmyelosuppression,pneumonia and hemorrhage were also higher than single Aza group(P<0.05).No statistical significance can be observed in 1-year OS between two groups(P>0.05).The same result can be seen in adjusted dose group.5.According to different drugs of combination,the concomitant drug group was divided into 2 groups,the one group was combined with low-dose chemotherapy and the other group was combined with BCL-2 inhibitor.There were no significant differences in total response rate and 1-year OS between two groups in the standard dose group and the adjusted dose group(P>0.05).As we mentioned above,the group combined with low-dose chemotherapy has a higher risk of gradeⅢorⅣmyelosuppression and pneumonia compare with combined BCL-2 inhibitor group(P<0.05).Conclusion:1.With same total dosage of Aza,both azacitidine 75 mg/(m~2·d)for 7 d and 100mg/d for 7-12 d can be used in elderly AML patients who cannot tolerate aggressive chemotherapy with similar overall effectiveness.2.With same total dosage of Aza,there is no significant difference in survival time between 75 mg/(m~2·d)and 100mg/d.3.With same total dosage of Aza,75 mg/(m~2·d)and 100mg/d regimen do not affect the incidence of hematological and non-hematological adverse reactions.4.The combination of Aza can increased patient efficiency and an increased incidence of serious adverse reactions and may not effect longer survival compared to monotherapy.5.Aza in combination with BCL-2 inhibitor not only has similar effect on CR,ORR,and OS,but also have higher safety compare with combination with low-dose chemotherapy. |
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