Introduction There is currently no standard treatment for relapsed and arsenic trioxide(ATO)-resistant acute promyelocytic leukemia(APL).Here,we report a case series of realgar-indigo naturalis formula(RIF)for the suc...Introduction There is currently no standard treatment for relapsed and arsenic trioxide(ATO)-resistant acute promyelocytic leukemia(APL).Here,we report a case series of realgar-indigo naturalis formula(RIF)for the successful treatment of patients with relapsed and ATO-resistant APL.Case presentation Two patients in the first relapse and one in the second relapse failed to achieve hematologic complete remission(HCR)when reinduced by ATO;the other five patients progressed to relapse during ATO-based regimens for post-remission therapy.These eight patients received RIF in three doses per day totaling 130 mg/kg(≤30 pills)as induction therapy and achieved HCR at a median time of 46.5 days.They received 5 years of post-remission therapy,which consisted of combined chemotherapy followed by RIF.During this period,the patients did not experience renal dysfunction or QT interval prolongation.At the last follow-up,three patients survived without relapse,two patients survived with a second or third relapse and third or fourth remission,and the other three patients relapsed for a third or fourth time and died.The 5-year overall survival and event-free survival rates were 75.0%(95%confidence interval[CI]:31.5–93.1)and 37.5%(95%CI:5.6–71.7),respectively.Conclusion RIF for induction therapy and RIF combined with chemotherapy for post-remission therapy may represent an effective and safe protocol for the treatment of patients with relapsed and ATO-resistant APL.展开更多
Objective:To evaluate the safety and efficacy of Compound Huangdai Tablets(Realgar-Indigo Naturalis formula,RIF)combined with all-trans retinoic acid(ATRA)to treat acute promyelocytic leukemia(APL).Methods:This study ...Objective:To evaluate the safety and efficacy of Compound Huangdai Tablets(Realgar-Indigo Naturalis formula,RIF)combined with all-trans retinoic acid(ATRA)to treat acute promyelocytic leukemia(APL).Methods:This study was registered in PROSPERO(CRD42018108118).The relevant literatures on RIF treatment of APL were systematically searched in the following databases:China National Knowledge Infrastructure,Wanfang,VIP Medical Information System,Chinese Biomedical Database,EMBASE,Cochrane Library,and PubMed.The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis.In addition,this study used the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL.Results:The study included 12 studies involving 775 APL patients.The Meta-analysis showed that there was no significant difference(P>0.05)between the RIF group and the arsenic trioxide(ATO)group for primary outcomes,secondary outcomes apart from liver dysfunction.The incidence of liver dysfunction(P=0.006)in the RIF group were significantly lower than those in the ATO group.In addition,the cost of maintenance therapy in the RIF group was significantly lower(P<0.05)than the ATO group.Besides,the active ingredients in RIF mainly act on targets proteins such as ACHE,NCOA2,RXRA,and then play a role in the treatment of APL through regulating multiple molecular mechanisms,such as TP53 regulates transcription of cell cycle genes,nuclear receptor transcription pathway.Conclusion:There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL.The oral RIF exposed patients to less risk,offered more convenience and had lower prices.RIF can treat APL by multi-target and multipathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells,and so on.Therefore,oral RIF in the treatment of APL is worthy of further research and development.展开更多
文摘Introduction There is currently no standard treatment for relapsed and arsenic trioxide(ATO)-resistant acute promyelocytic leukemia(APL).Here,we report a case series of realgar-indigo naturalis formula(RIF)for the successful treatment of patients with relapsed and ATO-resistant APL.Case presentation Two patients in the first relapse and one in the second relapse failed to achieve hematologic complete remission(HCR)when reinduced by ATO;the other five patients progressed to relapse during ATO-based regimens for post-remission therapy.These eight patients received RIF in three doses per day totaling 130 mg/kg(≤30 pills)as induction therapy and achieved HCR at a median time of 46.5 days.They received 5 years of post-remission therapy,which consisted of combined chemotherapy followed by RIF.During this period,the patients did not experience renal dysfunction or QT interval prolongation.At the last follow-up,three patients survived without relapse,two patients survived with a second or third relapse and third or fourth remission,and the other three patients relapsed for a third or fourth time and died.The 5-year overall survival and event-free survival rates were 75.0%(95%confidence interval[CI]:31.5–93.1)and 37.5%(95%CI:5.6–71.7),respectively.Conclusion RIF for induction therapy and RIF combined with chemotherapy for post-remission therapy may represent an effective and safe protocol for the treatment of patients with relapsed and ATO-resistant APL.
基金funded by the China Postdoctoral Science(No.2018M633332)
文摘Objective:To evaluate the safety and efficacy of Compound Huangdai Tablets(Realgar-Indigo Naturalis formula,RIF)combined with all-trans retinoic acid(ATRA)to treat acute promyelocytic leukemia(APL).Methods:This study was registered in PROSPERO(CRD42018108118).The relevant literatures on RIF treatment of APL were systematically searched in the following databases:China National Knowledge Infrastructure,Wanfang,VIP Medical Information System,Chinese Biomedical Database,EMBASE,Cochrane Library,and PubMed.The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis.In addition,this study used the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL.Results:The study included 12 studies involving 775 APL patients.The Meta-analysis showed that there was no significant difference(P>0.05)between the RIF group and the arsenic trioxide(ATO)group for primary outcomes,secondary outcomes apart from liver dysfunction.The incidence of liver dysfunction(P=0.006)in the RIF group were significantly lower than those in the ATO group.In addition,the cost of maintenance therapy in the RIF group was significantly lower(P<0.05)than the ATO group.Besides,the active ingredients in RIF mainly act on targets proteins such as ACHE,NCOA2,RXRA,and then play a role in the treatment of APL through regulating multiple molecular mechanisms,such as TP53 regulates transcription of cell cycle genes,nuclear receptor transcription pathway.Conclusion:There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL.The oral RIF exposed patients to less risk,offered more convenience and had lower prices.RIF can treat APL by multi-target and multipathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells,and so on.Therefore,oral RIF in the treatment of APL is worthy of further research and development.
