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
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： 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
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.
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 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.
