BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To explore the correlation between single nucleotide polymorphisms (SNPs) of ARID5B gene and the risk of acute lymphoblastic leukemia (ALL) and minimal residual disease (MRD) in children of Hui and Han nationality in Ningxia. METHODS: In this case-control study, 54 ALL children and control group with matched age, sex and nationality were detected for the polymorphism of ARID5B gene using fluorescence resonance energy transfer technique, and the susceptibility of different ALL genotypes and their correlation with MRD were analyzed. RESULTS: There were no significant differences in genotype and allele frequency of rs10994982, rs7089424, rs10740055, rs7073837, rs4245595 and rs7090445 between the two groups (P >0.05). At the locus of rs10821936, the frequencies of T/T genotype and T allele in ALL group were significantly higher than those in the control group (both P < 0.05). The C/C genotype of ARID5B gene SNP rs10821936 was a risk factor for early MRD positive in ALL children ( P < 0.05). CONCLUSION ARID5B gene SNP rs10821936 is related to the development of childhood ALL and MRD.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Polymorphism, Single Nucleotide ; Case-Control Studies ; Neoplasm, Residual/genetics* ; DNA-Binding Proteins/genetics* ; Transcription Factors/genetics* ; Genotype ; Genetic Predisposition to Disease ; Gene Frequency ; Child ; Male ; Female ; Alleles ; Risk Factors ; Child, Preschool

Neoplasm, Residual ; Humans ; Neoplasms/pathology* ; Consensus ; Prognosis ; Neoplasm Recurrence, Local ; China

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10^-3 mm² s^-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10^-3 mm² s^-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10^-3 mm² s^-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.
Male ; Humans ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Androgens ; Neoplasm, Residual ; Retrospective Studies ; Magnetic Resonance Imaging/methods* ; Diffusion Magnetic Resonance Imaging/methods*

OBJECTIVES: To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. RESULTS: Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×10⁹/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). CONCLUSIONS The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.
Child ; Humans ; Retrospective Studies ; Trisomy ; Prognosis ; Treatment Outcome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Neoplasm, Residual ; Disease-Free Survival

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Humans ; Female ; Prognosis ; Breast Neoplasms/surgery* ; Ki-67 Antigen/analysis* ; Neoadjuvant Therapy/methods* ; gamma Catenin ; Neoplasm, Residual ; Disease-Free Survival ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Humans ; Female ; Prognosis ; Breast Neoplasms/surgery* ; Ki-67 Antigen/analysis* ; Neoadjuvant Therapy/methods* ; gamma Catenin ; Neoplasm, Residual ; Disease-Free Survival ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To summarize the therapeutic effects of Chinese Children Leukemia Group-acute lymphoblastic leukemia (CCLG-ALL) 2018 regimen in children with T cell acute lymphoblastic leukemia (T-ALL) and to find out risk indicators for prognosis. Methods: This study was a prospective multicenter cohort study involving 299 newly diagnosed T-ALL children in 21 Grade A tertiary hospitals nationwide. All patients received CCLG-ALL 2018 regimen and clinical data for treatment efficacy evaluating was collected. Variables associated with event free survival (EFS) rate, overall survival (OS) rate and cumulative recurrence rate were evaluated by Lasso regression analysis (including variables selection, model construction and hazard ratio calculating). Results: A total of 299 newly diagnosed T-ALL children were included, accounting for 9.9% (299/3 026) of all ALL patients. Among these patients, there were 224 males and 75 females, and the age of onset was 7.0 (4.7, 10.6) years. All patients received CCLG-ALL 2018 regimen treatment. After 31.1 (17.3, 43.8) months follow-up, 3-year EFS, 3-year OS and cumulative recurrence rate of them were (83.2±2.7)%, (91.3±1.8)%, and (7.9±1.7)%, respectively. Minimal residual disease (MRD) greater than 10.00% on day 15 of induction therapy was a risk factor for EFS (HR=1.89, 95%CI 1.04-3.44), OS (HR=2.82, 95%CI 1.35-5.92), and cumulative recurrence rate (HR=3.05, 95%CI 1.46-6.34). Compared with the medium-risk group, the high-risk group had higher induction failure rate (5.2% (7/134) vs. 0 (0/145), P=0.016) and lower complete remission rate (88.8% (119/134) vs.97.9% (142/145),P=0.004). Most complications happened during induction therapy (95 cases), and the most common complication was serious infection (158 cases). Conclusions: CCLG-ALL 2018 regimen shows good prognosis. MRD greater than 10.00% on day 15 of induction therapy is a strong risk factor, which can indicate the prognosis in the early stage of the disease and guide the appropriate treatment.
Male ; Female ; Humans ; Child ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Disease-Free Survival ; Prospective Studies ; Cohort Studies ; East Asian People ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Neoplasm, Residual

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.
Humans ; Circulating Tumor DNA/genetics* ; Neoplasm, Residual/genetics* ; Biomarkers, Tumor/genetics* ; Neoplasm Recurrence, Local ; Prognosis