Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
Objective:To investigate the efficacy and prognosis of venetoclax combined with hypomethylating agents(HMAs)in the treatment of relapsed/refractory acute myeloid leukemia(AML).Methods:From June 2021 to February 2022,1...Objective:To investigate the efficacy and prognosis of venetoclax combined with hypomethylating agents(HMAs)in the treatment of relapsed/refractory acute myeloid leukemia(AML).Methods:From June 2021 to February 2022,14 patients with relapsed/refractory AML were treated with venetoclax combined with HMAs,among which nine patients were treated with venetoclax+azacytidine,while five patients were treated with venetoclax+decitabine.The efficacy of the treatments was observed,and the patients were followed up.Results:All patients received one to five courses of treatment,in which the median course of treatment was three;four cases achieved CR and another four achieved PR,with NR in six cases;there was no treatment-related death.There were seven deaths up to the end of the follow-up period,all of which were progressive deaths at the end of the disease,and the overall survival rate was 50.00%.All the patients experienced different degrees of nausea,vomiting,and myelosuppression(Grade Ⅱ–Ⅳ),nine patients had Grade 3–4 hematological adverse reactions,and seven patients had infection.Conclusion:Venetoclax combined with hypomethylating agents is effective in the treatment of relapsed/refractory AML,with good prognosis,and some patients may even achieve CR.Although bone marrow suppression is serious with this combination,it is well tolerated.展开更多
Background The prognosis for relapsed or refractory acute myeloid leukemia(RR-AML)in children is poor,and the preferred salvage chemotherapy is unclear.One regimen is cladribine,cytarabine,and granulocyte-colony stimu...Background The prognosis for relapsed or refractory acute myeloid leukemia(RR-AML)in children is poor,and the preferred salvage chemotherapy is unclear.One regimen is cladribine,cytarabine,and granulocyte-colony stimulating factor(CLAG),but little is known about its efficacy and safety in children with RR-AML.Methods We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1,2015 and April 1,2018,or conventional induction between August 1,2011 and April 1,2018.Patients were followed up to March 31,2019.Patients underwent allogeneic stem cell transplantation(allo-SCT)or chemotherapy after the induction of complete remission(CR).The CR rate,survival,and side effects were analyzed.Results The CR rate for induction was 66.7%after one cycle and 75.0%after two cycles of the CLAG regimen in 12 children.The nine children who received conventional chemotherapy had a CR rate of 22.2%after one cycle and 33.3%after two cycles(P=0.087 vs.CLAG).The 3-year event-free survival(EFS)of the CLAG group and the conventional treatment group were 44.4±15.7%and 22.2±13.8%(P=0.112).The 3-year overall survival of the two groups were 59.5±16.2%and 22.2%±13.8%(P=0.057).The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7±19.2%and 25.0±21.7%(P=0.015).A single case of chemotherapy-related death was recorded.Conclusion Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML.Allo-SCT after CR may improve the long-term outcome in these patients.展开更多
Background： Studies of haploidentical-related donor （HRD） stem cell transplantation using a combination of peripheral blood stem cells （PBSCs） and bone marrow as the graft have reported encouraging results for pa...Background： Studies of haploidentical-related donor （HRD） stem cell transplantation using a combination of peripheral blood stem cells （PBSCs） and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia （AML）. Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation （HRD-PBSCT） for relapsed/refractory AML were analyzed. Methods： We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs （n = 36）. Results： Thirty-one （86.1%） patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease （aGVHD） in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation （range： 10-1700 days）, reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age 〉40 years were independent risk factors for inferior disease-free survival or overall survival （P 〈 0.05）. The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions： Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.展开更多
Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-r...Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-related quality of life(HR-QoL)after total therapy,which included allogeneic hematopoietic stem cell transplantation(allo-HSCT),and prophylactic donor lymphocyte infusion(DLI)in the early phase after transplantation,followed bymultiplemeasurable residual disease(MRD)and graft-versus-host disease(GvHD)-guided DLIs.Methods:Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study.If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse,severe infection,organ failure,and active GvHD at the time of planned DLI,prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen(HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT.Subsequently,multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.Results:A total of 105 patients were eligible.Eighty-seven patients received prophylactic DLI(group B),while 18 did not receive prophylactic DLI(group A).Among 105 patients,the cumulative incidence of grade 2-4 acute GvHD and chronic GvHDwas 40.6%(95%confidence interval[CI]=30.6%-50.6%)and 73.3%(95%CI=67.4%-79.2%),respectively.The cumulative incidence of relapse(CIR),transplant-related mortality(TRM),and leukemia-free survival(LFS)at 5 years after transplantation were 31.5%(95%CI=21.9%-41.1%),22.1%(95%CI=11.3%-32.9%),and 46.4%(95%CI=36.8%-56.0%),respectively.In group B,the CIR,TRM,and LFS at 5 years after transplantation were 27.6%(95%CI=17.6%-37.6%),21.6%(95%CI=11.2%-32.0%),and 50.8%(95%CI=40.0%-61.6%),respectively.At the end of follow-up,48 patients survived,and more than 90%of survivors had satisfactory recoveries of HR-QoL.Conclusions:Our study indicated that total therapy is not only associated with decreased CIR,comparable TRM,and better long-term LFS,but also with satisfactoryHR-QoL for refractory or relapsed AML,compared with those of standard of care therapy reported previously.Therefore,total therapymay be an optimized therapeutic strategy for refractory or relapsed AML.展开更多
Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were tre...Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three展开更多
Background： The E-26 transformation-specific related gene （ERG） is frequently expressed in cytogenetically normal acute myeloid leukemia （CN-AML）. Herein, we performed a meta-analysis to investigate the relations...Background： The E-26 transformation-specific related gene （ERG） is frequently expressed in cytogenetically normal acute myeloid leukemia （CN-AML）. Herein, we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML. Methods： A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016. A total of 667 CN-AML patients were collected from seven published studies. Of the 667 patients underwent intensive chemotherapy, 429 had low expression of ERG and 238 had high expression of ERG. Summary odds ratio （OR） and the 95% confidence interval （（~7） for the ERG expression and CN-AML were calculated using fixed- or random-effects models. Heterogeneity was assessed using Chi-squared-based Q-statistic test and/2 statistics. All statistical analyses were performed using R.3.3.1 software packages （R Foundation for Statistical Computing, Vienna, Austria） and RevManS.3 （Cochrane Collaboration, Copenhagen, Denmark）. Results： Overall patients with high ERG expression had a worse relapse （OR = 2.5127. 95% CI： 1.5177-4.1601, P = 0.0003） and lower complete remission （OR = 0.3495, 95% CI： 0.2418-0.5051, P 〈 0.0001）. With regard to the known molecular markers, both internal tandem duplications of the fms-related tyrosine kinase 3 gene （OR =3.8634, 95% CI： 1.8285-8.1626, P = 0.004） and brain and acute leukemia, cytoplasmic （OR = 3.1538, 95% CI： 2.0537-4.8432, P 〈 0.0001） were associated with the ERG expression. In addition, the results showed a statistical significance between French-American-British （FAB） classification subtype （minimally differentiated AML and AML without maturation, OR = 4.7902, 95% CI： 2.7772-8.2624, P 〈 0.0001; acute monocytic leukemia, OR = 0.2324, 95% CI： 0.0899-0.60（/6, P = 0.0026） and ERG expression. Conclusion： High ERG expression might be used as a strong adverse prognostic factor in CN-AML.展开更多
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
文摘Objective:To investigate the efficacy and prognosis of venetoclax combined with hypomethylating agents(HMAs)in the treatment of relapsed/refractory acute myeloid leukemia(AML).Methods:From June 2021 to February 2022,14 patients with relapsed/refractory AML were treated with venetoclax combined with HMAs,among which nine patients were treated with venetoclax+azacytidine,while five patients were treated with venetoclax+decitabine.The efficacy of the treatments was observed,and the patients were followed up.Results:All patients received one to five courses of treatment,in which the median course of treatment was three;four cases achieved CR and another four achieved PR,with NR in six cases;there was no treatment-related death.There were seven deaths up to the end of the follow-up period,all of which were progressive deaths at the end of the disease,and the overall survival rate was 50.00%.All the patients experienced different degrees of nausea,vomiting,and myelosuppression(Grade Ⅱ–Ⅳ),nine patients had Grade 3–4 hematological adverse reactions,and seven patients had infection.Conclusion:Venetoclax combined with hypomethylating agents is effective in the treatment of relapsed/refractory AML,with good prognosis,and some patients may even achieve CR.Although bone marrow suppression is serious with this combination,it is well tolerated.
基金This study was supported by a grant from Shanghai Science and Technology Committee Projects No.14411950602 and No.18ZR1431200.
文摘Background The prognosis for relapsed or refractory acute myeloid leukemia(RR-AML)in children is poor,and the preferred salvage chemotherapy is unclear.One regimen is cladribine,cytarabine,and granulocyte-colony stimulating factor(CLAG),but little is known about its efficacy and safety in children with RR-AML.Methods We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1,2015 and April 1,2018,or conventional induction between August 1,2011 and April 1,2018.Patients were followed up to March 31,2019.Patients underwent allogeneic stem cell transplantation(allo-SCT)or chemotherapy after the induction of complete remission(CR).The CR rate,survival,and side effects were analyzed.Results The CR rate for induction was 66.7%after one cycle and 75.0%after two cycles of the CLAG regimen in 12 children.The nine children who received conventional chemotherapy had a CR rate of 22.2%after one cycle and 33.3%after two cycles(P=0.087 vs.CLAG).The 3-year event-free survival(EFS)of the CLAG group and the conventional treatment group were 44.4±15.7%and 22.2±13.8%(P=0.112).The 3-year overall survival of the two groups were 59.5±16.2%and 22.2%±13.8%(P=0.057).The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7±19.2%and 25.0±21.7%(P=0.015).A single case of chemotherapy-related death was recorded.Conclusion Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML.Allo-SCT after CR may improve the long-term outcome in these patients.
基金This work was partially supported by grants from the Beijing Nova Program （2011114）, the National Natural Science Foundation of China （No. 30800482, 30971297, 81102242, 81000221, 81270610, 81470010, 81170518, 81370666, and 90919044）, the Beijing Natural Science Foundation of China （No. 7102147, 7172200, and 7132217）, the High and New Technology Program of the PLA （2010gxjs091）, the Capital Medical Development Scientific Research Fund （No. 2007-2040）, the National Public Health Grand Research Foundation （No 201202017）, the Public Health Project （Z111 10706731 1070）, and the National 973 Project of China （No. 2005CB522400）.
文摘Background： Studies of haploidentical-related donor （HRD） stem cell transplantation using a combination of peripheral blood stem cells （PBSCs） and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia （AML）. Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation （HRD-PBSCT） for relapsed/refractory AML were analyzed. Methods： We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs （n = 36）. Results： Thirty-one （86.1%） patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease （aGVHD） in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation （range： 10-1700 days）, reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age 〉40 years were independent risk factors for inferior disease-free survival or overall survival （P 〈 0.05）. The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available. Conclusions： Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.
基金Innovative Research Groups of the National Natural Science Foundation of China,Grant/Award Number:81621001National Key Research and Development Program of China,Grant/Award Number:2017YFA0104500National Natural Science Foundation of China,Grant/Award Number:81930004。
文摘Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-related quality of life(HR-QoL)after total therapy,which included allogeneic hematopoietic stem cell transplantation(allo-HSCT),and prophylactic donor lymphocyte infusion(DLI)in the early phase after transplantation,followed bymultiplemeasurable residual disease(MRD)and graft-versus-host disease(GvHD)-guided DLIs.Methods:Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study.If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse,severe infection,organ failure,and active GvHD at the time of planned DLI,prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen(HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT.Subsequently,multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.Results:A total of 105 patients were eligible.Eighty-seven patients received prophylactic DLI(group B),while 18 did not receive prophylactic DLI(group A).Among 105 patients,the cumulative incidence of grade 2-4 acute GvHD and chronic GvHDwas 40.6%(95%confidence interval[CI]=30.6%-50.6%)and 73.3%(95%CI=67.4%-79.2%),respectively.The cumulative incidence of relapse(CIR),transplant-related mortality(TRM),and leukemia-free survival(LFS)at 5 years after transplantation were 31.5%(95%CI=21.9%-41.1%),22.1%(95%CI=11.3%-32.9%),and 46.4%(95%CI=36.8%-56.0%),respectively.In group B,the CIR,TRM,and LFS at 5 years after transplantation were 27.6%(95%CI=17.6%-37.6%),21.6%(95%CI=11.2%-32.0%),and 50.8%(95%CI=40.0%-61.6%),respectively.At the end of follow-up,48 patients survived,and more than 90%of survivors had satisfactory recoveries of HR-QoL.Conclusions:Our study indicated that total therapy is not only associated with decreased CIR,comparable TRM,and better long-term LFS,but also with satisfactoryHR-QoL for refractory or relapsed AML,compared with those of standard of care therapy reported previously.Therefore,total therapymay be an optimized therapeutic strategy for refractory or relapsed AML.
文摘Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three
基金The study was supported by grants from the Collaborative Innovation Projects of Science and Technology Department of Zhejiang （No. 2014F50014）, and Natural Science Foundation of Zhejiang Province （No. LY 13H310004）.
文摘Background： The E-26 transformation-specific related gene （ERG） is frequently expressed in cytogenetically normal acute myeloid leukemia （CN-AML）. Herein, we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML. Methods： A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016. A total of 667 CN-AML patients were collected from seven published studies. Of the 667 patients underwent intensive chemotherapy, 429 had low expression of ERG and 238 had high expression of ERG. Summary odds ratio （OR） and the 95% confidence interval （（~7） for the ERG expression and CN-AML were calculated using fixed- or random-effects models. Heterogeneity was assessed using Chi-squared-based Q-statistic test and/2 statistics. All statistical analyses were performed using R.3.3.1 software packages （R Foundation for Statistical Computing, Vienna, Austria） and RevManS.3 （Cochrane Collaboration, Copenhagen, Denmark）. Results： Overall patients with high ERG expression had a worse relapse （OR = 2.5127. 95% CI： 1.5177-4.1601, P = 0.0003） and lower complete remission （OR = 0.3495, 95% CI： 0.2418-0.5051, P 〈 0.0001）. With regard to the known molecular markers, both internal tandem duplications of the fms-related tyrosine kinase 3 gene （OR =3.8634, 95% CI： 1.8285-8.1626, P = 0.004） and brain and acute leukemia, cytoplasmic （OR = 3.1538, 95% CI： 2.0537-4.8432, P 〈 0.0001） were associated with the ERG expression. In addition, the results showed a statistical significance between French-American-British （FAB） classification subtype （minimally differentiated AML and AML without maturation, OR = 4.7902, 95% CI： 2.7772-8.2624, P 〈 0.0001; acute monocytic leukemia, OR = 0.2324, 95% CI： 0.0899-0.60（/6, P = 0.0026） and ERG expression. Conclusion： High ERG expression might be used as a strong adverse prognostic factor in CN-AML.
