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With the great progress of precise medicine for lymphatic malignancies, minimal residual diseases (MRD) play an increasingly important role in their evaluation of treatment response, prognosis judgement, treatment decision guidance, and recurrence prediction. At present, nearly a thousand articles on hematological malignancies related to MRD detection are published annually. At the 65th American Society of Hematology annual meeting in 2023, nearly 500 articles on the application of MRD detection in the diagnosis and treatment of lymphatic malignancies cover a wide and rich range of content. This paper reviews the oral reports of MRD detection in acute lymphocytic leukemia, chronic lymphocytic leukemia, multiple myeloma and lymphoma.
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Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.
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ABSTRACT Introduction: B cell acute lymphoblastic leukemia-lymphoma (B-ALL) accounts for approximately 75% of ALL cases and is observed in children and adults. Recent advances in disease diagnosis, stratification and prognostication have led to a better characterization of different subgroups of ALL. Notwithstanding the significant improvement in the complete remission rate of B-ALL, patients with minimal residual disease (MRD) and relapsed/refractory (R/R) settings suffer from poor outcomes. Hypothesis: However, novel therapies, such as agents targeting tyrosine kinases or the CD20 molecule, combination therapies and improved supportive care, have changed the treatment landscape of B-ALL. Method and results: Meanwhile, blinatumomab has been FDA-approved for MRD-positive or R/R B-ALL patients. Blinatumomab is a bispecific T cell engager containing the CD3 and CD19 that recognize domains redirecting cytotoxic T cells to lyse B cells. Promising outcomes, including long-term overall survival and improved MRD-negative response rates, have been reported in patients who received this drug. Adding blinatumomab to new ALL regimens seems promising for achieving better outcomes in poor prognosis B-ALL patients. Nevertheless, the neurotoxicity and cytokine release syndrome are the two major adverse events following the blinatumomab therapy. Conclusion: This review summarizes the function and effectiveness of blinatumomab in R/R and MRD positive B-ALL patients. Furthermore, blinatumomab's positive and negative aspects as a novel therapy for B-ALL patients have been briefly discussed.
Subject(s)
Humans , Male , Female , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma , LymphomaABSTRACT
A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)
Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/therapy , Immunophenotyping/instrumentation , Neoplasm, Residual/diagnosis , Flow Cytometry/instrumentationABSTRACT
@#ObjectiveTo develop a highly sensitive method for detection of mutation of FMS-like tyrosine kinase-3-tyrosine kinase domain(FLT3-TKD)of acute myeloid leukemia(AML)and apply to the monitor of minimal residual disease(MRD).MethodsRecombinant plasmids containing wild FLT3 and mutant FLT3-D835Y were constructed respectively and mixed at certain ratios.The obtained standard plasmids with mutation rates of 50%,1%,0.1% and 0% respectively were determined by restriction fragment length polymorphism(RFLP)in combination with Sanger method.The plasmid DNA standards and blood DNA standards,at various FLT3-D835Y mutation rates,were determined by the developed method to verify the sensitivity.The genomic DNA samples of patients with AML before and after treatment were determined by the developed method to monitor the MRD.ResultsSequencing proved that both the recombinant plasmids containing wild FLT3 and mutant FLT3-D835Y were constructed correctly.The sensitivity of developed method increased to 0.1% through Sanger method combined with digestion with EcoR Ⅴ/Xho Ⅰ and recovery of mutant fragments in determination of purified plasmid DNA and collected blood DNA samples.MRD was detected in the peripheral blood sample of a patients with AML in complete remission period by the developed method but not by Sanger method.ConclusionA highly sensitive method for detection of FLT3-TKD mutation was developed,which was of an important clinical significance in guiding the treatment of AML and monitoring the MRD in complete remission period.
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How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Neoplasm, Residual/pathology , Biomarkers, Tumor/genetics , Computational BiologyABSTRACT
Minimal residual disease (MRD) has been used not only for relapse prediction, prognosis re-classification and directing pre-emptive therapy of patients with acute leukemia, but also in the field of therapy for patients with other hematological malignancies or solid tumors. A deep understanding of the intension and extension of MRD is important for exploring novel methods for accurate prediction of relapse and consummating the individualized intervention strategies for malignant tumors.
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Minimal residual disease (MRD) has been used for warning of relapse and guiding the therapy selection for hematological malignancies including acute leukemia. Based on MRD-related content reported at the 64th American Society of Hematology (ASH) Annual Meeting, this article discusses the progress of MRD-directed individualized therapy for hematological malignancies with a primary focus on acute myeloid leukemia.
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Acute lymphoblastic leukemia (ALL) is a malignancy originating from B-/T-lineage lymphoid progenitor cells. With the continuous development of new drugs as well as therapeutic regimens, adult ALL patients have improved complete remission rates and overall survival rates, but the survival rate of patients after relapse remains low. The positive minimal residual disease after complete remission is an important reason for relapse. Although minimal residual disease monitoring has been found to be important in predicting patients prognosis in recent years, the uniform stratified treatment protocols have not yet been developed in the clinical practice of adult ALL. This article reviews the prognostic significance of minimal residual disease monitoring at different time points, as well as the progress of removal methods of minimal residual disease.
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B-cell lymphoma is a group of heterogeneous hematologic malignant tumors originating from B cells, and it could be divided into invasive B-cell lymphoma and inert B-cell lymphoma. Currently, although disease remission rate has reached a high level, some patients still develop disease relapse or progression, thus, it is important to regularly monitor the disease and early identify the recurrence. At present, the recurrence of lymphoma mainly depends on imaging and clinical evaluation. However, some studies have shown that the minimal residual disease (MRD) monitoring based on flow or second-generation sequencing can provide a more accurate assessment of the depth of remission, predict the disease prognosis, and identify the early disease recurrence. This review summarizes the application of MRD in indolent lymphoma and aggressive lymphoma, mainly including the detection methods of MRD, research status and the application prospect of MRD in different lymphomas.
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Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.
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Objective:To assess the clinical significance of next-generation sequencing (NGS)-based IGH/ IGK gene rearrangement analysis versus flow cytometry (FCM) in diagnosing minimal residual disease (MRD) of children with acute B-cell lymphoblastic leukemia (B-ALL). Methods:Clinical data, NGS-MRD and FCM-MRD findings at the initial diagnosis and after induction chemotherapy of 85 children diagnosed as B-ALL in Children′s Hospital of Nanjing Medical University from July 2019 to July 2021, were retrospectively analyzed.The sensitivity of the two methods, and the positive rate were compared by χ2 test or Fisher′ s test.The correlation was identified by Spearman correlation analysis. Results:Dominant clone sequences were detected in all children at the initial diagnosis by NGS, while selection markers were identified by FCM in 75(88.2%) patients.Positive MRD rate detected by NGS-MRD was significantly higher than that of FCM-MRD at the same time point after induction chemotherapy[31.8%(27/85) vs.9.4%(8/85), P<0.001]. Compared with those of FCM-MRD, NGS-MRD had good sensitivity (100.0%), specificity (75.3%) and negative predictive value (100.0%), and the positive predictive value was 29.6%.MRD results detected by NGS were consistent with that of FCM ( r=0.569, P<0.001). By July 27, 2022, 2 patients with NGS-MRD (+ )FCM-MRD (-)relapsed during maintenance chemotherapy. Conclusions:NGS is highly consistent with FCM in the detection of MRD in children with B-ALL, which is more sensitive.The combination of NGS-MRD and FCM-MRD benefits more in monitoring MRD in children with B-ALL after induction chemotherapy.
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Objective:To explore the diagnostic value and problems of artificial intelligence (AI) bone marrow cell recognition technology in the detection of minimal residual disease (MRD) of leukemia.Methods:A total of 65 cases with minimal residual disease of leukemia confirmed by flow cytometry from the Hematology Medical Center of Xinqiao Hospital affiliated to the Army Medical University (AMMU) from November 1 to December 31, 2020 were collected. The bone marrow Wright′s staining smears were obtained, and all bone marrow smears were scanned and classified automatically without artificial intervention by the analysis system based on Artificial Intelligence platform (morphogo). AI-MRD was defined to positive when the proportion of primary cells was more than 3%. According to the number of AI automatic recognition cells, the cases were divided into 18 cases of less than 500 (L500), 35 cases of 500 to 1900 (between 500 and 1900, B1900), and 12 cases of more than 1900 (M1900), no overlap or omission between groups. Kappa consistency test was performed on the results of artificial intelligence test and the results of flow cytometry for minimal residual disease of leukemia (MFC-MRD) in each group. The receiver operating characteristic curve (ROC) of the artificial intelligence test results of each group of patients was drawn based on the MFC-MRD results, and the sensitivity, specificity and accuracy of the area under the curve (AUC) value and AI results were calculated.Results:After grouping according to the number of cells automatically recognized by AI, the detection results of L500 group were MFC-MRD+/AI-MRD+7 cases, MFC-MRD+/AI-MFC-2 cases, MFC-MRD-/AI-MRD+6 cases, MFC-MRD-/AI-MRD-3 cases; In B1900 group, MFC-MRD+/AI-MRD+13 cases, MFC-MRD+/AI-MFC-6 cases, MFC-MRD-/AI-MRD+6 cases, MFC-MRD-/AI-MRD-10 cases; The results of M1900 group were MFC-MRD+/AI-MRD+5 cases, MFC-MRD+/AI-MFC-0 cases, MFC-MRD-/AI-MRD+1 case, MFC-MRD-/AI-MRD-6 cases. Taking MFC-MRD as the determination standard, the sensitivity of AI-MRD detection in L500 group, B1900 group and M1900 group was 53.8%, 68.4% and 83.3%, the specificity was 60%, 62.5% and 100%, the accuracy was 55.6%, 65.7% and 91.7%, and the AUC value were 0.568 P=0.654, 0.678 P=0.069,1.000 P=0.000. Conclusions:This study preliminarily explored the diagnostic value and problems of AI bone marrow cell recognition in the detection of minimal residual disease of leukemia. It was confirmed that when 3% of the proportion of blasts in AI cell classification is set>3% as the positive threshold of AI-MRD, the consistency between AI and MFC-MRD detection increases with the increase of the number of cells recognized by AI.
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Objective:Central nervous system leukemia(CNSL)is one of the main causes of recurrence and death in patients with acute leukemia.This study aims to dynamically monitor minimal residual disease(MRD)in cerebrospinal fluid and bone marrow of patients with different types of acute leukemia by flow cytometry(FCM),and to compare the timeliness and consistency of MRD detection between the 2 methods to further explore the application value of monitoring MRD in cerebrospinal fluid. Methods:A total of 199 patients with acute leukemia admitted to the Guangdong Provincial people's Hospital between October 2018 and January 2022 were retrospectively analyzed,and multiparametric FCM method was adopted to summarize and analyze MRD in cerebrospinal fluid of patients with different types of leukemia and MRD in cerebrospinal fluid and bone marrow specimens of the same patients,and its role in assessing the prognostic value of patients was discussed. Results:Among the 199 acute leukemia cases,a total of 31 cases(15.58%)were positive MRD in the cerebrospinal fluid,of which 18 cases(58%)were detected earlier than the corresponding bone marrow specimens.Among the 19 patients with acute T lymphoblastic leukemia,134 patients with acute B lymphoblastic leukemia,and 46 patients with acute myeloid leukemia counted,there were 4,18,and 9 patients with positive MRD in the cerebrospinal fluid.The Kappa value of the concordance test between the results of cerebrospinal fluid MRD and bone marrow MRD in different types of acute leukemia was only 0.156,demonstrating a low concordance between them. Conclusion:Dynamic monitoring of cerebrospinal fluid MRD by FCM can be used as a monitoring index for central nervous system leukemia,and monitoring cerebrospinal fluid can detect MRD earlier compared with bone marrow,which complements each other as a sensitive index for evaluating prognosis with significant guidance in clinic.
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Circulating tumor DNA (ctDNA) is emerging as a novel biomarker for tumor evaluation, offering advantages such as high sensitivity and specificity, minimal invasiveness, and absence of radiation. Currently, various techniques including gene sequencing and PCR are employed for ctDNA detection. The utilization of ctDNA for monitoring minimal residual disease (MRD) enables comprehensive assessment of tumor status and early identification of tumor recurrence, achieving a remarkable detection sensitivity of 0.01%. Therefore, ctDNA holds promise as a biomarker for early diagnosis, treatment response monitoring, and prognosis prediction in solid tumors. This article reviews the commonly used methods for detecting ctDNA and their advantages in evaluating tumor MRD and guiding clinical diagnosis and treatment.
Subject(s)
Humans , Circulating Tumor DNA/genetics , Neoplasm, Residual/genetics , Biomarkers, Tumor/genetics , Neoplasm Recurrence, Local , PrognosisABSTRACT
OBJECTIVE@#To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis.@*METHODS@#The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed.@*RESULTS@#There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026).@*CONCLUSION@#In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.
Subject(s)
Male , Female , Child , Humans , Infant , Child, Preschool , Adolescent , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Neoplasm, Residual/diagnosis , Clinical Relevance , Retrospective Studies , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Burkitt Lymphoma , Basic Helix-Loop-Helix Transcription Factors/therapeutic useABSTRACT
With the advent of precision medicine, next-generation sequencing (NGS) is playing an increasingly important role in clinical oncology diagnosis and treatment with its advantages of high sensitivity, high accuracy, high efficiency and operability. NGS reveals the genetic characteristics of acute leukemia(AL) patients by screening for specific disease-causing genes to identify occult as well as complex genetic mutations in patients with AL, leading to early diagnosis and targeted drug therapy for AL patients, as well as to predict disease recurrence by detecting mnimal residual disease (MRD) and analyzing mutated genes to determine patient prognosis. NGS plays an increasingly important role in the diagnosis, treatment and prognosis assessment in AL, providing a direction for the pursuit of precision medicine. This paper reviews the research progress of NGS in AL.
Subject(s)
Humans , High-Throughput Nucleotide Sequencing , Leukemia, Myeloid, Acute/genetics , Acute Disease , Mutation , Recurrence , Neoplasm, Residual/geneticsABSTRACT
OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.
Subject(s)
Humans , Retrospective Studies , Flow Cytometry , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Bone Marrow , Neoplasm, Residual , RecurrenceABSTRACT
For locally advanced unresectable non-small cell lung cancer (NSCLC), the standard regimen is concurrent chemoradiotherapy (CCRT) followed by consolidation immunotherapy. Nevertheless, the majority of patients will experience recurrence. Traditional imaging examination has its limitations of passively identifying recurrence, unable to forecast the risk in advance. Minimal residual disease (MRD) based on circulating tumor DNA (ctDNA) has become a novel tumor biomarker. Existing studies have demonstrated that the levels of ctDNA initially increase and then decrease during CCRT for NSCLC. Monitoring ctDNA-MRD can not only robustly predict recurrence, but also guide the consolidation immunotherapy, evaluate the efficacy and predict clinical prognosis. Furthermore, ctDNA-MRD can be a reliable biomarker to explore other effective treatments. However, few ctDNA-MRD clinical studies related to guiding consolidation therapy have been performed, with small sample size and low-level evidence. The value of ctDNA-MRD still needs to be confirmed by prospective randomized studies.
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Acute myeloid leukemia (AML) is a group of highly-heterogeneous clonal diseases. Chemotherapy and hematopoietic stem cell transplantation are considered as effective treatment for AML. For high-risk AML patients, allogeneic hematopoietic stem cell transplantation is an effective therapeutic option. However, some AML patients may still face the problem of disease recurrence after hematopoietic stem cell transplantation. A majority of recurrent patients cannot be effectively treated by chemotherapy or secondary transplantation, which is the main cause of death after allogeneic hematopoietic stem cell transplantation. Therefore, it is of significance to strengthen follow-up of AML patients after allogeneic hematopoietic stem cell transplantation and implement appropriate measures to prevent postoperative recurrence. In this article, the monitoring, drug prevention and cell therapy of recurrence after allogeneic hematopoietic stem cell transplantation in high-risk AML patients were reviewed, aiming to provide reference for improving clinical prognosis of high-risk AML patients undergoing allogeneic hematopoietic stem cell transplantation.