Acute myeloid leukemia(AML)is characterized by the accumulation of cytogenetic and molecular abnormalities.Isocitrate dehydrogenase 1 and 2(IDH1/2)mutations occur in 11%to 20%of adults with AML.The outcome of IDH1/2-m...Acute myeloid leukemia(AML)is characterized by the accumulation of cytogenetic and molecular abnormalities.Isocitrate dehydrogenase 1 and 2(IDH1/2)mutations occur in 11%to 20%of adults with AML.The outcome of IDH1/2-mutated AML is heterogeneous and affected by co-mutational patterns.We retrospectively analyzed 118 patients with IDH1/2-mutated AML who were retrieved from 1597 patients newly diagnosed with AML and treated with intensive chemotherapy.Univariate analysis revealed the NPM1 mutation was a favorable factor(p=0.019)for overall survival(OS),whereas the DNMT3A mutation was consistently associated with a poor outcome(3-year OS,52.0%;3-year relapse-free survival[RFS],44.8%;and 3-year cumulative incidence of relapse[CIR],42.6%).Interestingly,the DNMT3A mutation still identified patients with a poorer prognosis,even when measurable residual disease(MRD)was negative after 2 courses of chemotherapy.In a multivariate regression model,age,DNMT3A mutation and MRD positivity were retained as independent adverse markers for OS,RFS,and CIR.In the absence of the DNMT3A or FLT3-ITD mutations,the NPM1 mutation identified patients with a very favorable OS(3-year OS,96.3%and 86.3%,respectively).Finally,hematopoietic stem cell transplantation in first complete remission significantly improved RFS(p=0.015)and there was a trend toward improvement in OS(p=0.282)for patients with the DNMT3A mutation but it did not benefit 2 subgroups with the IDH1/2+/NPM1+/DNMT3A−and IDH1/2+/NPM1+/FLT3-ITD−genotypes.In summary,this study provides a reference for risk stratification and treatment implications for patients with IDH1/2-mutated AML as well as for comparison with results of IDH inhibitor-or venetoclax-based combination therapy.展开更多
Acute myeloid leukemia(AML)with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis.However,its clinical and molecular features remain poorly defined.We determined the clinicopathological,g...Acute myeloid leukemia(AML)with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis.However,its clinical and molecular features remain poorly defined.We determined the clinicopathological,genomic,and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center.Thirty-six AML patients harboring FUS::ERG were identified,with an incidence rate of 0.3%.These patients were characterized by high lactate dehydrogenase levels(median:838.5 U/L),elevated bone marrow blast counts(median:71.5%),and a CD56-positive immunophenotype(94.3%).Notably,we found that RTK–RAS GTPase(RAS)pathway genes,including NRAS(33%)and PTPN11(24%),were frequently mutated in this subtype.Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt(PI3K-Akt),mitogen-activated protein kinase(MAPK),and RAS signaling pathways and upregulation of BCL2,the target of venetoclax,in FUS::ERG AML compared to RUNX1::RUNX1T1 AML,a more common AML subtype with good prognosis.The median event-free survival in patients with FUS::ERG AML was 11.9(95%confidence interval[CI]:9.0–not available[NA])months and the median overall survival was 18.2(95%CI:12.4–NA)months.Allogeneic hematopoietic stem cell transplantation failed to improve outcomes.Overall,the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.展开更多
1.INTRODUCTION With rapid developments in genetic engineering,tumor immunology,and cellular engineering,chimeric antigen receptor T cell(CAR-T)cell therapy has become a novel immunotherapy for oncology and other medic...1.INTRODUCTION With rapid developments in genetic engineering,tumor immunology,and cellular engineering,chimeric antigen receptor T cell(CAR-T)cell therapy has become a novel immunotherapy for oncology and other medical fields.1 The promising results of CD19 CAR-T treating B-cell malignancies were reported.2,3 Simultaneously,there existed many adverse events,the most reported of which including B-cell aplasia,hematological toxicity,cytokine release syndrome(CRS),and immune effector-cell–associated neurotoxicity syndrome(ICANS),3,4 but there is still lack of reports demonstrating the impact of CD19 CAR-T on the ABO blood group potency of patient’s serum.展开更多
To The Editor:The role of measurable residual disease(MRD)in prognosis and treatment in acute myeloid leukemia(AML)is evolving.Studies have demonstrated the correlation between MRD and risks of relapse in adult AML:pe...To The Editor:The role of measurable residual disease(MRD)in prognosis and treatment in acute myeloid leukemia(AML)is evolving.Studies have demonstrated the correlation between MRD and risks of relapse in adult AML:persistently positive MRD after induction is associated with a high risk of relapse,1,2 and these patients should consider allogeneic transplantation(allo-Hematopoietic Stem Cell Transplantation(HSCT))and clinical trial,even in favorable-risk groups.However,because of the financial issue or lack of suitable transplant donors,many of the patients could not receive allo-HSCT,so how to prolong the relapse-free survival of these patients remains a challenge.Platzbecker et al treated MRD-positive patients with azacytidine(AZA),and found pre-emptive therapy with AZA can prevent or substantially delay hematological relapse in MRD-positive patients with MDS(myelodysplastic syndrome)or AML who are at a high risk of relapse.展开更多
基金supported by the National Key Research and Development Program of China(2021YFC2500300)the National Natural Science Foundation of China(82341213,82000131)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-041).
文摘Acute myeloid leukemia(AML)is characterized by the accumulation of cytogenetic and molecular abnormalities.Isocitrate dehydrogenase 1 and 2(IDH1/2)mutations occur in 11%to 20%of adults with AML.The outcome of IDH1/2-mutated AML is heterogeneous and affected by co-mutational patterns.We retrospectively analyzed 118 patients with IDH1/2-mutated AML who were retrieved from 1597 patients newly diagnosed with AML and treated with intensive chemotherapy.Univariate analysis revealed the NPM1 mutation was a favorable factor(p=0.019)for overall survival(OS),whereas the DNMT3A mutation was consistently associated with a poor outcome(3-year OS,52.0%;3-year relapse-free survival[RFS],44.8%;and 3-year cumulative incidence of relapse[CIR],42.6%).Interestingly,the DNMT3A mutation still identified patients with a poorer prognosis,even when measurable residual disease(MRD)was negative after 2 courses of chemotherapy.In a multivariate regression model,age,DNMT3A mutation and MRD positivity were retained as independent adverse markers for OS,RFS,and CIR.In the absence of the DNMT3A or FLT3-ITD mutations,the NPM1 mutation identified patients with a very favorable OS(3-year OS,96.3%and 86.3%,respectively).Finally,hematopoietic stem cell transplantation in first complete remission significantly improved RFS(p=0.015)and there was a trend toward improvement in OS(p=0.282)for patients with the DNMT3A mutation but it did not benefit 2 subgroups with the IDH1/2+/NPM1+/DNMT3A−and IDH1/2+/NPM1+/FLT3-ITD−genotypes.In summary,this study provides a reference for risk stratification and treatment implications for patients with IDH1/2-mutated AML as well as for comparison with results of IDH inhibitor-or venetoclax-based combination therapy.
基金supported by the National Key Research and Development Program(2021YFC2500300)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-041)+3 种基金Tianjin Municipal Science and Technology Commission Grant(23JCYBJC01050)National Natural Science Foundation of China(81830005,82000131)Clinical Research Foundation of National Clinical Research Center for Blood Diseases(2023NCRCA0101)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2022-RW320-14)。
文摘Acute myeloid leukemia(AML)with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis.However,its clinical and molecular features remain poorly defined.We determined the clinicopathological,genomic,and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center.Thirty-six AML patients harboring FUS::ERG were identified,with an incidence rate of 0.3%.These patients were characterized by high lactate dehydrogenase levels(median:838.5 U/L),elevated bone marrow blast counts(median:71.5%),and a CD56-positive immunophenotype(94.3%).Notably,we found that RTK–RAS GTPase(RAS)pathway genes,including NRAS(33%)and PTPN11(24%),were frequently mutated in this subtype.Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt(PI3K-Akt),mitogen-activated protein kinase(MAPK),and RAS signaling pathways and upregulation of BCL2,the target of venetoclax,in FUS::ERG AML compared to RUNX1::RUNX1T1 AML,a more common AML subtype with good prognosis.The median event-free survival in patients with FUS::ERG AML was 11.9(95%confidence interval[CI]:9.0–not available[NA])months and the median overall survival was 18.2(95%CI:12.4–NA)months.Allogeneic hematopoietic stem cell transplantation failed to improve outcomes.Overall,the high incidence of RTK–RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.
基金the CAMS Innovation Fund for Medical Sciences(Grant no.2021-1-I2M-041)Tianjin Municipal Science and Technology Commission Grant(Grant no.20JCZDJC00120).
文摘1.INTRODUCTION With rapid developments in genetic engineering,tumor immunology,and cellular engineering,chimeric antigen receptor T cell(CAR-T)cell therapy has become a novel immunotherapy for oncology and other medical fields.1 The promising results of CD19 CAR-T treating B-cell malignancies were reported.2,3 Simultaneously,there existed many adverse events,the most reported of which including B-cell aplasia,hematological toxicity,cytokine release syndrome(CRS),and immune effector-cell–associated neurotoxicity syndrome(ICANS),3,4 but there is still lack of reports demonstrating the impact of CD19 CAR-T on the ABO blood group potency of patient’s serum.
基金funded by Tianjin Clinical Research Center:Construction of Tianjin Clinical Research Center for Blood Diseases(2016.4-2019.12)(15ZXLCSY00010)National Key Research and Development Program of China(2021YFC2500003).
文摘To The Editor:The role of measurable residual disease(MRD)in prognosis and treatment in acute myeloid leukemia(AML)is evolving.Studies have demonstrated the correlation between MRD and risks of relapse in adult AML:persistently positive MRD after induction is associated with a high risk of relapse,1,2 and these patients should consider allogeneic transplantation(allo-Hematopoietic Stem Cell Transplantation(HSCT))and clinical trial,even in favorable-risk groups.However,because of the financial issue or lack of suitable transplant donors,many of the patients could not receive allo-HSCT,so how to prolong the relapse-free survival of these patients remains a challenge.Platzbecker et al treated MRD-positive patients with azacytidine(AZA),and found pre-emptive therapy with AZA can prevent or substantially delay hematological relapse in MRD-positive patients with MDS(myelodysplastic syndrome)or AML who are at a high risk of relapse.
