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1.
Article in Chinese | WPRIM | ID: wpr-928729

ABSTRACT

OBJECTIVE@#To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen.@*METHODS@#106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children.@*RESULTS@#The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon.@*CONCLUSION@#Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.


Subject(s)
Blood Platelets , Burkitt Lymphoma , Child , Disease-Free Survival , Humans , Neoplasm, Residual/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Retrospective Studies
2.
Article in Chinese | WPRIM | ID: wpr-928724

ABSTRACT

OBJECTIVE@#To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease.@*METHODS@#The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis.@*RESULTS@#There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections.@*CONCLUSION@#The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.


Subject(s)
Animals , Body Weight , Disease Models, Animal , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma
3.
Article in Chinese | WPRIM | ID: wpr-928717

ABSTRACT

OBJECTIVE@#To establish 10-color fluorescent antibody combination panels for the detection of minimal residual disease (MRD) of acute myeloid leukemia (AML) in our laboratory and discuss the value of clinical application.@*METHODS@#According to the antigen expression characteristics of leukemia cells of incipient AML patients, MRD in bone marrow were detected by multiparameter flow cytometry, and the test results were compared with both bone marrow cell morphology and PCR results, then 10-color fluorescent antibody combination panels in our lab for MRD detection was determined.@*RESULTS@#The immunophenotypic characteristics of 392 incipient patients with AML in the First Affiliated Hospital of Zhengzhou University were analyzed, among them 357 (91.07%) cases showed abnormal immunophenotypes, which mainly included cross-lineage expression, cross-stage expression, deficiency of antigen expression or abnormal antigen intensity and other abnormal expression. The 10-color fluorescent antibody combination panels established according to abnormal immunophenotypic characteristics of leukemia cells were applied for detecting MRD in 156 patients with AML, the positive rate (43.6%) was higher than 26.8% of morphology, and the results were highly consistent with PCR detection results (96.49%), moreover, the recurrence rate of MRD positive patients (86.96%) was significantly higher than 5.75% of MRD negative patients. Therefore, this method could truly reflect the load of leukemia cells and prompt change of disease condition.@*CONCLUSION@#Multiparameter flow cytometry can detect various abnormal immunophenotypes of AML. The 10-color fluorescent antibody combination panels in our lab based on the characteristics of antigens expression in leukemia cells can well detect MRD of leukemia cells, so as to predict relapse and provide basis for clinical treatment.


Subject(s)
Bone Marrow , Flow Cytometry/methods , Humans , Immunophenotyping , Leukemia, Myeloid, Acute/diagnosis , Neoplasm, Residual/diagnosis
4.
Article in Chinese | WPRIM | ID: wpr-928641

ABSTRACT

OBJECTIVES@#To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).@*METHODS@#A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors.@*RESULTS@#Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05).@*CONCLUSIONS@#Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.


Subject(s)
Acute Disease , Antigens, Neoplasm/therapeutic use , Child , Humans , Neoplasm, Residual/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis
5.
Article in Chinese | WPRIM | ID: wpr-939681

ABSTRACT

OBJECTIVE@#To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry.@*METHODS@#MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival (OS) time and relapse-free survival (RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis.@*RESULTS@#ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly higher than that of MRD-negative patients [52.45% (75/143 cases) vs 35.97% (50/139 cases), P=0.005]. The patients in MRD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group (P<0.005). Survival analysis showed that OS and RFS time of patients with MRD persistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation (P<0.005). There was no significant difference in OS and RFS between MRD negative to positive group and MRD persistent positive group (P>0.005), either between MRD persistent negative group and MRD positive to negative group (P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level (95%CI: 1.000-1.013, P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation (HSCT) was 9.694 times higher than that in patients who received HSCT (95%CI: 1.720-54.651, P=0.010), and in the high-risk group was 5.848 times higher than that in the low-risk group (95%CI: 1.418-24.121, P=0.015).@*CONCLUSION@#The prognosis of AML patients with different MRD changes is significantly different. No matter MRD-positive or MRD-negative at the initial remission, dynamic detection of MRD after treatment is more helpful to accurately guide treatment.


Subject(s)
Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/drug therapy , Neoplasm, Residual/diagnosis , Prognosis , Recurrence , Transplantation, Homologous
6.
Article in Chinese | WPRIM | ID: wpr-939672

ABSTRACT

OBJECTIVE@#To establish the droplet digital PCR (ddPCR) assay for the detection of NPM1 type A mutation in patients with acute myeloid leukemia (AML), and to evaluate its specificity, sensitivity and its value in clinical application.@*METHODS@#NPM1 mutant and wildtype plasmids were used to verify the performance of ddPCR. Both ddPCR and Sanger sequencing were used to detect the bone marrow samples of 87 AML patients, which were confirmed by next generation sequencing (NGS). Moreover, NPM1 mutation burden was dynamically monitored in five patients by ddPCR.@*RESULTS@#The limit of blank (LOB) of ddPCR established for NPM1 mutation detection was 1.1 copies/μl, and the limit of detection (LOD) was 2.43 copies/μl, which had good linearity. Among the 87 newly diagnosed AML patients, ddPCR identified seventeen cases positive for NPM1 mutation (19.5%), which was consistent with Sanger sequencing. NGS confirmed 12 positive cases, including 8 of type A mutations, 2 of type D mutations, and 2 of rare type mutations. The results of dynamic monitoring of NPM1 mutation burden in 5 patients showed that the NPM1 mutation burden decreased obviously even close to 0, when patients achieve complete remission after chemotherapy. However, the mutation burden was increased again at the time of relapse.@*CONCLUSION@#In this study, we established a ddPCR method for detection of NPM1 mutation with good sensitivity and repeatability, which can be used for screening NPM1 mutation in newly diagnosed AML patients and for minimal residual disease monitoring after remission in positive AML patients to guide treatment.


Subject(s)
Humans , Leukemia, Myeloid, Acute/therapy , Mutation , Nuclear Proteins/genetics , Nucleophosmin , Polymerase Chain Reaction , Prognosis
7.
Article in Chinese | WPRIM | ID: wpr-933478

ABSTRACT

To explore prognostic factors in intermediate-risk acute myeloid leukemia (AML) patients with minimal residual disease (MRD) negativity (MRD<0.1%,MRD-)receiving autologous hematopoietic stem cell transplantation (auto-HSCT).A total of 59 intermediate-risk AML patients with MRD-were treated with auto-HSCT from January 2015 to September 2021 at Affiliated People′s Hospital of Ningbo University. The clinical data and laboratory results were collected retrospectively. Efficacy, clinical outcome and prognostic factors were analyzed. Univariate analysis was conducted by using log-rank test, the multivariate analysis by Cox proportional risk model.Among 59 patients, there were 27 males and 32 females with median age of 55 (31-69) years old.The median follow-up was 761(317-1 861)days. The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 76.1%±11.4% and 73.4%±11.6% respectively.The univariate analysis showed that age older than 50 years, TET2 gene mutation (TET2 +), achieving MRD negativity over 30 days (MRD 30+) were unfavorable factors of OS ( χ2=6.20, 33.20, 7.18; P=0.013,<0.001, 0.007). TET 2+, WT1 gene mutation (WT1 +), CD34 +cells<2×10 6/kg, MRD 30+were negative factors of EFS ( χ2=17.29, 4.47, 3.94, 9.393; P<0.001, 0.035, 0.047, 0.002).Multivariate analysis showed that MRD 30+, TET2 + were independent prognostic factors of OS and EFS (OS: HR=9.251, 25.839, P=0.036, 0.001;EFS: HR=5.851, 9.199, P=0.043, 0.002). Intermediate-risk AML patients with MRD 30+or TET2 + have very poor prognosis after auto-HSCT. Alternative regimens should be investigated.

8.
Article in Chinese | WPRIM | ID: wpr-930422

ABSTRACT

Objective:To explore the clinical significance of the MYCN gene, PHOX2B gene and plasma cell-free DNA (cfDNA) in risk stratification and predicting the prognosis of high-risk neuroblastoma (NB). Methods:This was a prospective study involving 94 high-risk NB children admitted to Beijing Children′s Hospital, Capital Medical University from August 2017 to December 2018.Relative levels of MYCN and PHOX2B and cfDNA at diagnosis, and 4 and 6 cycles of chemotherapy were detected, and their differences were compared by the Chi- square test.Kaplan-Meier survival analysis was performed to explore their prognostic potential in high-risk NB. Results:Among the 94 high-risk NB children, 14 cases (14.9%) had MYCN amplification, 76 cases (80.8%) had positive expression of PHOX2B and 56 cases (59.6%) had cfDNA level higher than 100 μg/L.The proportion of high lactate dehydrogenase (LDH, ≥1 500 U/L) level in the MYCN gene amplification group (6/14 cases) was higher than that in the normal group (9/80 cases) ( P=0.009). The proportion of multi-site metastasis (54/76 cases) and high neuron specific enolase (NSE) level (NSE≥370 μg/L, 37/76 cases) in PHOX2B positive group were significantly higher than those in the negative group (5/14 cases, 2/14 cases) ( P=0.015, 0.020). The proportion of high LDH and high NSE in high cfDNA concentration (≥229.6 μg/L)group (13/37 cases, 28/37 cases) were significantly higher than those in low cfDNA concentration group (2/48 cases, 10/48 cases) (all P<0.001). With the decreased tumor burden during the treatment, the copy number of PHOX2B gene and cfDNA level were significantly lower than those at the initial diagnosis [0 (0-719.6) copies vs.1 723.5 (0-186 000.0) copies; 19.0 (1.1-225.5) μg/L vs.200.6 (8.0-5 247.4) μg/L, all P<0.001]. The 2-year event-free survival (EFS) rate of the MYCN gene amplification group was significantly lower than that of the normal group[(33.3±13.1)% vs.(58.5±7.1)%, P=0.020]. The 2-year EFS rate of PHOX2B positive group was significantly lower than that of the negative group[(47.9±7.1)% vs.(79.1±11.1)%, P=0.043]. EFS rate in high cfDNA concentration group was significantly lower than that in cfDNA low concentration group[(38.6±9.8)% vs.( 71.7±8.2)%, P=0.001]. After 6 cycles of chemotherapy, EFS rate in the PHOX2B positive group was significantly lower than that in the negative group [(16.7±14.4)% vs.( 60.6±6.6)%, P=0.014]; which was significantly lower in the Metaiodobenzylguanidine (MIBG) positive group than that of the negative group[(35.2±11.7)% vs.(65.8±7.1)%, P=0.037]. The MYCN gene and cfDNA concentration were not correlated with the prognosis of high-risk NB.Survival analysis of the combination of PHOX2B and MYCN gene ( PHOX2B+ /MIBG + , PHOX2B+ or MIBG + , PHOX2B-/MIBG -) showed a significant difference in the survival among three groups[0 vs.(53.6±1.2)% vs.(65.5±7.4)%, P=0.003]. Conclusions:The MYCN and PHOX2B gene and cfDNA concentration are of significance in risk stratification and predicting the prognosis of high-risk NB.Compared with the MYCN gene and cfDNA concentration, the PHOX2B gene is more suitable for monitoring the curative effect of chemotherapy on high-risk NB.A combined analysis of PHOX2B gene and MIBG before treatment can be more accurate in evaluating the treatment effect and residual lesions.

9.
Chinese Journal of Hematology ; (12): 221-228, 2022.
Article in Chinese | WPRIM | ID: wpr-929561

ABSTRACT

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .


Subject(s)
B-Lymphocytes , Graft vs Host Disease , HLA Antigens/genetics , Haplotypes , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Retrospective Studies , Siblings
10.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(3): 332-340, July-Sept. 2021. tab, graf
Article in English | LILACS | ID: biblio-1346264

ABSTRACT

Abstract Introduction: The minimal residual disease (MRD) status plays a crucial role in the treatment of acute lymphoblastic leukemia (ALL) and is currently used in most therapeutic protocols to guide the appropriate therapeutic decision. Therefore, it is imperative that laboratories offer accurate and reliable results through well standardized technical processes by establishing rigorous operating procedures. Method: Our goal is to propose a monoclonal antibody (MoAb) panel for MRD detection in ALL and provide recommendations intended for flow cytometry laboratories that work on 4-color flow cytometry platforms. Results and conclusion: The document includes pre-analytical and analytical procedures, quality control assurance, technical procedures, as well as the information that needs to be included in the reports for clinicians.


Subject(s)
Humans , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Flow Cytometry
11.
Article in Chinese | WPRIM | ID: wpr-912532

ABSTRACT

Objective:To investigate the value of minimal residual disease (MRD) in prediction of prognosis in acute lymphoblastic leukemia (ALL) patients with or above complete remission 2 (CR2) underwent.Methods:A retrospective analysis was performed on 201 ALL patients who received allogeneic stem cell transplantation (allo-SCT) and pretransplant disease status ≥CR2 in Peking University People′s Hospital from January 2009 to December 2018. MRD was measured by multi-parameter flow cytometry at 1 month before transplantation and 1 month, 2 months, 3 months, 4 months, 6 months, 9 months or 12 months after transplantation. To investigate the influence of dynamic changes of MRD before and after transplantation on prognosis.Results:201 ALL patients, including 126 males and 75 females, with a median age of 18 years. The 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), leukemia-free survival (LFS) and overall survival (OS) of all cases were 34%, 16%, 50%, and 56%, respectively. Positive pre-SCT MRD patients with higher 3-year CIR (47% vs 26%, P=0.003), lower 3-year LFS (40% vs 55%, P=0.047) and OS (42% vs 60%, P=0.065) than those with negative one. Subjects with positive post-MRD had higher 3-year CIR (73% vs 22%, P<0.001) and lower 3-year LFS (28% vs 56%, P=0.005) and OS (32% vs 60%, P=0.040) compared with those with negative one. Multivariate analysis showed that both pre-MRD and post-MRD were associated with higher CIR ( HR=1.823, P=0.018; HR=3.474, P<0.001), lower LFS ( HR=1.779, P=0.007; HR=2.185, P=0.001) and OS ( HR=1.609, P=0.034; HR=1.970, P=0.001). Negative pre-and post-SCT MRD group had lower 3-year CIR (17%, 42%, 82%; P<0.001) and higher 3-year LFS (61%, 44%, 18%; P<0.001) and OS (63%, 47%, 27%; P<0.001) compared with those unrisen post-SCT MRD group, and increased post-SCT MRD group. Multivariate analysis showed that pre-and post-SCT MRD dynamics were associated with CIR, LFS and OS ( P<0.01 for all) independently. The pre-and post-SCT MRD dynamics could better distinguish CIR (C=0.669) from that of pre-SCT MRD (C=0.587) and post-SCT MRD (C=0.629). Conclusion:Our data suggest that pre-SCT MRD, post-SCT MRD and the dynamic peri-SCT MRD could be used to predict transplant outcome of ALLpatients with or above CR2 who underwent allo-SCT.

12.
Article in Chinese | WPRIM | ID: wpr-912513

ABSTRACT

With the improvement of detective sensitivity, the application of circulating tumor DNA (ctDNA) has gradually expanded from advanced tumors to early stage. Recently, the detection of minimal residual disease (MRD) using ctDNA in solid tumors has attracted particular attention. MRD testing has shown an essential role in the risk assessment of solid tumor recurrence and treatment guidance. However, the MRD detection strategies used in each study are different, and the conclusions drawn as well. This paper reviewed the research progress of ctDNA for MRD detection in solid tumor, as well as its challenges of detection technology and application, in order to promote the clinical transformation and standardized application of MRD detection by ctDNA in solid tumors.

13.
Clin. biomed. res ; 41(3): 192-198, 20210000. graf
Article in English | LILACS | ID: biblio-1344765

ABSTRACT

Introduction: Treatment of childhood acute lymphoblastic leukemia (ALL) is based on risk stratification. This study aimed to assess the agreement between risk group classifications in the different childhood ALL treatment protocols used in a referral hospital in southern Brazil. Methods: We retrospectively reviewed the medical records of patients aged 1 to 18 years with B-cell ALL treated at a hospital from January 2013 to April 2017. Agreement between risk classifications was assessed by the kappa coefficient. Results: Seventy-five patients were analyzed. There was poor agreement between risk stratification by GBTLI 2009 and BFM 95 protocols (kappa = 0.22; p = 0.003) and by GBTLI 2009 and IC-BFM 2002 protocols (kappa = 0.24; p = 0.002). Risk group distribution was 13.3% for low risk, 32.0% for intermediate risk, and 54.7% for high risk based on stratification by the GBTLI 2009 protocol, and 28.0% for low risk, 42.7% for intermediate risk, and 29.3% for high risk based on stratification by the IC-BFM 2002 protocol. Overall survival was 68.6%. Conclusion: This study provides numerous points to ponder about the treatment of leukemia in Brazil. The percentage of patients classified as high risk in our sample was higher than that reported in the international literature. This difference, however, had no impact on overall survival, which was shorter than that reported in the international literature. (AU)


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Antineoplastic Combined Chemotherapy Protocols , Risk Factors , Cancer Survivors
14.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(4): 348-355, Oct.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1142973

ABSTRACT

ABSTRACT Background: The minimal residual disease (MRD) is the most important prognostic factor for acute lymphoblastic leukemia (ALL) in children. This study aimed to investigate the influence of detecting the MRD by the multiparametric flow cytometry (MFC) at day 15 (D15) of the induction on the analysis of the risk group classifications of the different childhood ALL treatment protocols used in a referral hospital in southern Brazil. Method: We retrospectively reviewed the medical records of patients with B-cell ALL, aged 1 to 18 years, treated at a hospital from January 2013 to April 2017. Main results: Seventy-five patients were analyzed. Regarding the MRD by the MFC at D15, the analyses showed statistical significance when the MRD was grouped into three categories, < 0.1%, 0.1-10%, and > 10%, with the following distribution: 30.7%, 52.0%, and 17.3%, respectively. There was a significant association between D15 MRD-MFC < 0.1% and the likelihood of dying or relapsing and between D15 MRD-MFC > 10% and the likelihood of dying or relapsing. The cumulative hazard ratio for the relapse of patients with D15 MRD-MFC < 0.1%, 0.1-10%, and > 10% was 19.2%, 59.8%, and 80.1%, respectively. Conclusion: Our analysis suggests D15 MRD-MFC < 0.1% as a cut-off point for patients with more favorable outcomes and that the MRD at D15 in risk classifications is particularly useful for the stratification of patients with a more favorable prognosis.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Prognosis , Referral and Consultation , Leukemia, Biphenotypic, Acute/therapy , Risk Factors , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma
15.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 269-274, July-Sept. 2020. ilus
Article in English | LILACS | ID: biblio-1134046

ABSTRACT

ABSTRACT Recent advances in chronic lymphocytic leukemia (CLL) includes description of disease genomic landscape, inclusion of prognostic relevant genetic tests in CLL workflow and evaluation of minimal residual disease (MRD)1 in parallel with the increase availability of novel therapy agents.In this review, the theoretical and practical aspects of response assessment have been discussed. These are based on updated recommendations of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) for genetic tests (TP53 mutation and IGHV status) and flow cytometry analysis for CLL. Methodological approaches and interpretation of results were also discussed.2,3


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Genes, p53 , Neoplasm, Residual , Flow Cytometry , Mutation
16.
Chinese Journal of Hematology ; (12): 16-22, 2020.
Article in Chinese | WPRIM | ID: wpr-799072

ABSTRACT

Objective@#To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR1) and negative minimal residual disease (MRD-) .@*Methods@#A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR1/MRD- from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy.@*Results@#A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR1/MRD- was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes.@*Conclusion@#Allo-HSCT for candidate patients without further consolidation when CR1/MRD- was attained was feasible.

17.
Frontiers of Medicine ; (4): 354-364, 2019.
Article in English | WPRIM | ID: wpr-771263

ABSTRACT

The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN- α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n = 47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P = 0.377) and 9.1% and 0.0% (P = 0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P = 0.891) and 84.3% and 84.6% (P = 0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.

18.
Chinese Journal of Hematology ; (12): 111-116, 2019.
Article in Chinese | WPRIM | ID: wpr-810463

ABSTRACT

Objective@#To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive.@*Methods@#Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored.@*Results@#Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively.@*Conclusion@#The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.

19.
Chinese Journal of Hematology ; (12): 105-110, 2019.
Article in Chinese | WPRIM | ID: wpr-810462

ABSTRACT

Objective@#To investigate the prognostic significance of detection of minimal residual disease after first induction treatment (MRD1) in adult acute lymphoblastic leukemia (ALL) patients treated with autologous stem cell transplantation (auto-HSCT).@*Methods@#The clinical data of 87 ALL patients who underwent auto-HSCT during February 2006 to April 2017 with MRD1 detection data by flow cytometry were analyzed retrospectively. The relationship between MRD1 and relapse and survival of ALL patients after auto-HSCT was studied.@*Results@#Of 87 patients, 26 (29.9%) were MRD1 positive. The proportion of high-risk immunophenotype (pro-B, pro-T, pre-T, mature T) was significantly higher in MRD1-positive patients than that in MRD1 negative patients (34.6% vs 14.5%, P=0.038). There was no significant difference between positive and negative MRD1 patients at age, sex, lineage (T/B), immunophenotype (standard risk/high risk), high white blood cell count (B-ALL>30×109/L or T-ALL>100×109/L), high-risk chromosome/gene ratio, the time from first complete remission to transplantation and pre-treatment regimen. The 5-year overall survival (OS) and leukemia-free survival (LFS) in MRD1 negative and positive patients were 72.7% vs 47.3% (P=0.004) and 75.7% vs 29.6% (P<0.001), respectively. Multivariate analysis showed that positive MRD1 was an independent risk factor for OS (HR=3.007, 95% CI 1.256-7.200, P=0.013) , and positive MRD1 and high-risk immunophenotype were risk factors for LFS (HR=3.986, 95% CI 1.813-8.764, P=0.001; HR=2.981, 95% CI 1.373-6.473, P=0.006) .@*Conclusions@#Auto-HSCT could not reverse the poor prognosis of MRD1 positive patients. Auto-HSCT treatment is optional for patients with MRD1 negative and maintaining MRD1 negative status during intensive therapy.

20.
Chinese Journal of Hematology ; (12): 584-588, 2019.
Article in Chinese | WPRIM | ID: wpr-805658

ABSTRACT

Objective@#To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) .@*Methods@#A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc.@*Results@#①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD-) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD- rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD- status. ②The 2-year PFS rate of patients with MRD- status was significantly higher than that of MRD+ status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD+) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD- status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD-status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD- status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD- duration (median MRD- duratio: 25 months vs 10 months, P=0.034) .@*Conclusion@#Our findings supported MRD+ status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD- status also played a significant role in evaluation of prognosis, while loss of MRD-status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

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