Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subseque...Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.展开更多
We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-A...We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.展开更多
Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD...Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo?HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo?HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre?HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre?HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo?SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre?HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo?SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo?SCT, those without persistent MRD underwent haplo?SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia?free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001). Conclusion: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo?SCT settings.展开更多
Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of...Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT （haplo-SCT） for patients with acquired severe aplastic anemia （SAA）. Methods： A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results： A total of 126 patients （97.7%） achieved neutrophil engraftment, and 121 patients （95.7%） achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease （GVHD） was 32.6%. After a median follow-up of 842 （range： 124-4110） days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14＋ （P = 0.018） and CD34＋ cells （P 〈 0.001） were associated with a successful platelet engraftment. A successthl platelet was associated with superior survival （P 〈 0.001）. No correlation of other cell components with outcomes was observed. Conclusions： These results provide evidence and explain that higher doses ofCD34＋ and CD 14＋ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.展开更多
Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains unclear.Studies on the role of MTA2 mostly concentrated on it as a component of the Nu...Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains unclear.Studies on the role of MTA2 mostly concentrated on it as a component of the NuRD complex,which functions via the NuRD complex to inhibit the transcription of downstream target genes.2 Whether MTA2 could directly exert transcriptional regulation independent of the transcription factor remains unclear and is the focus of the present study.展开更多
Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this st...Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.Methods:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study.We aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of relapse.The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.Results:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet engraftment.The 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,respectively.Multivariate analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above variables.The 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk score.Conclusion:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.展开更多
基金supported by Grants from the Key Program of the National Natural Science Foundation of China(81230013)the Major State Basic Research Development Program of China(973 Program,2013CB733701)+2 种基金the Nature Science Foundation of China(81170483,81570130 and 81370639)the Beijing Municipal Science and Technology Commission(Z141100000214011)support from the NIHR Biomedical Research Centre funding scheme
文摘Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.
基金the Beijing Municipal Science and Technology Commission(No.Z181100009618032)the National Natural Science Foundation of China(Nos.:81870141,82070185,81670186).
文摘We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.
文摘Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo?HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo?HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre?HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre?HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo?SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre?HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo?SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo?SCT, those without persistent MRD underwent haplo?SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia?free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001). Conclusion: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo?SCT settings.
基金This work was financially supported （in part） by a grant from the National Natural Science Foundation of China （No. 81470342）.
文摘Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT （haplo-SCT） for patients with acquired severe aplastic anemia （SAA）. Methods： A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results： A total of 126 patients （97.7%） achieved neutrophil engraftment, and 121 patients （95.7%） achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease （GVHD） was 32.6%. After a median follow-up of 842 （range： 124-4110） days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14＋ （P = 0.018） and CD34＋ cells （P 〈 0.001） were associated with a successful platelet engraftment. A successthl platelet was associated with superior survival （P 〈 0.001）. No correlation of other cell components with outcomes was observed. Conclusions： These results provide evidence and explain that higher doses ofCD34＋ and CD 14＋ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.
基金This study was supported by the National Science and Technology Major Project(Grant No.2018ZX09736005)National Natural Science Foundation of China(grant no.81872374,81972629,81972746,82073205,82072709,81902441)+1 种基金Tianjin Science and Technology Project(Grant No.19JCJQJC63200)the Taishan Scholars Program of Shandong Province(Grant No.tsqn201909193).
文摘Dear editor,MTA2 is associated with invasively malignant phenotypes in many types of cancers,1 but the molecular mechanism remains unclear.Studies on the role of MTA2 mostly concentrated on it as a component of the NuRD complex,which functions via the NuRD complex to inhibit the transcription of downstream target genes.2 Whether MTA2 could directly exert transcriptional regulation independent of the transcription factor remains unclear and is the focus of the present study.
基金supported by grants from the Beijing Municipal Science and Technology Commission(No.Z181100009618032)the National Key Research and Development Program of China(No.2017YFA0104500)+1 种基金the National Natural Science Foundation of China(Nos.81670186,82070185)the Peking University Clinical Scientist Program(No.BMU2019LCKXJ003)。
文摘Background:For patients with B cell acute lymphocytic leukemia(B-ALL)who underwent allogeneic stem cell transplantation(allo-SCT),many variables have been demonstrated to be associated with leukemia relapse.In this study,we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.Methods:A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People’s Hospital from December 2010 to December 2015 were enrolled in this retrospective study.We aimed to evaluate the factors associated with transplant outcomes after allo-SCT,and establish a risk score to identify patients with different probabilities of relapse.The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.Results:All patients achieved neutrophil engraftment,and 95.4%of patients achieved platelet engraftment.The 5-year cumulative incidence of relapse(CIR),overall survival(OS),leukemia-free survival(LFS),and non-relapse mortality were 20.7%,70.4%,65.6%,and 13.9%,respectively.Multivariate analysis showed that patients with positive post-transplantation minimal residual disease(MRD),transplanted beyond the first complete remission(≥CR2),and without chronic graft-versus-host disease(cGVHD)had higher CIR(P<0.001,P=0.004,and P<0.001,respectively)and worse LFS(P<0.001,P=0.017,and P<0.001,respectively),and OS(P<0.001,P=0.009,and P<0.001,respectively)than patients without MRD after transplantation,transplanted in CR1,and with cGVHD.A risk score for predicting relapse was formulated with the three above variables.The 5-year relapse rates were 6.3%,16.6%,55.9%,and 81.8%for patients with scores of 0,1,2,and 3(P<0.001),respectively,while the 5-year LFS and OS values decreased with increasing risk score.Conclusion:This new risk score system might stratify patients with different risks of relapse,which could guide treatment.
