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Zhongguo Dang Dai Er Ke Za Zhi =... May 2024To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors.
OBJECTIVES
To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors.
METHODS
A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022.
RESULTS
The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (<0.05). The children with platelet count >400×10/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (<0.05).
CONCLUSIONS
The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×10/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.
Topics: Humans; Male; Female; Child; Child, Preschool; Prognosis; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Adolescent; Infant; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38802906
DOI: 10.7499/j.issn.1008-8830.2311060 -
F1000Research 2022Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL...
BACKGROUND
Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells.
METHODS
NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were harvested for adhesion assay and migration assay . In experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry.
RESULTS
Both anaesthetics reduced migration and homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy.
CONCLUSION
Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing and via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.
Topics: Animals; Receptors, CXCR4; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Humans; Female; Cell Line, Tumor; Mice; Propofol; Sevoflurane; Osteopontin; Cell Movement; Anesthetics, General; Mice, Inbred C57BL; Drug Resistance, Neoplasm
PubMed: 38798305
DOI: 10.12688/f1000research.125877.2 -
Medicina (Kaunas, Lithuania) Apr 2024: Leukemia, characterized by abnormal leukocyte production, exhibits clonal origin from somatic mutations. Globally, it ranked 15th in cancer incidence in 2020, with...
: Leukemia, characterized by abnormal leukocyte production, exhibits clonal origin from somatic mutations. Globally, it ranked 15th in cancer incidence in 2020, with higher prevalence in developing countries. In Mexico, it was the ninth most frequent cancer. Regional registries are vital for understanding its epidemiology. This study aims to analyze the prevalence and age-standardized incidence rates of leukemias in a tertiary care hospital in the Mexican Bajio region. : Leukemia cases from 2008-2018 were analyzed, and 535 medical records were included in this study. The prevalence, distribution, and age-specific incidence rate of different types and subtypes of leukemia were determined according to sex and age groups. : Overall, 65.79% consisted of lymphocytic leukemia, 33.64% of myeloid leukemia, and 0.56% of monocytic leukemia. No significant sex-based differences were found, but age-specific patterns were observed. Leukemia distribution by age revealed significant associations. Lymphocytic leukemia dominated in the pediatric population, particularly acute lymphocytic leukemia, while myeloid leukemia shifted towards adulthood. Age-specific incidence patterns showed, first, that lymphocytic leukemia is the most common leukemia in pediatric ages, and second, there is a shift from acute lymphocytic leukemia dominance in pediatric ages to myeloid leukemia incidence in late adulthood, emphasizing nuanced epidemiological dynamics. : Acute leukemia cases occurred with high prevalence in our study population, with a high incidence in pediatric and adulthood populations, especially for acute lymphocytic leukemia, showing a (<18 years) 153.8 age-standardized incidence rate in the pediatric group, while in the adult population, the age-standardized rate was 59.84. In the age-specific analysis, we found that the childhood group (5-9 years) were the most affected by acute lymphocytic leukemia in the pediatric population, while in the adult population, the early-adulthood group (15-29 years) were the most affected age group. In contrast, chronic myeloid leukemia affected both adults and the pediatric populations, while chronic lymphocytic leukemia and monocytic leukemia were exclusive to adults. The study underscores the need for tailored diagnostic, treatment, and preventive strategies based on age, contributing valuable insights into the leukemia epidemiology of the Bajio region.
Topics: Humans; Mexico; Male; Female; Child; Adolescent; Adult; Child, Preschool; Middle Aged; Incidence; Aged; Infant; Leukemia; Young Adult; Prevalence; Age Factors; Aged, 80 and over; Registries
PubMed: 38792914
DOI: 10.3390/medicina60050731 -
Journal of Clinical Medicine May 2024Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare cutaneous disorder associated with various hematologic malignancies, most commonly chronic...
Eosinophilic dermatosis of hematologic malignancy (EDHM) is a rare cutaneous disorder associated with various hematologic malignancies, most commonly chronic lymphocytic leukemia. Detailed clinicopathologic studies of EDHM are lacking and the pathogenesis remains enigmatic. Initially thought to be a hypersensitivity reaction to insect stings, subsequent reports have challenged this understanding. The prognostic implications of EDHM remain unclear. A retrospective clinicopathologic study was performed on patients diagnosed with EDHM. Hematologic and dermatologic data were reviewed. Histologic specimens were re-evaluated and lesions were classified into acute/subacute, fully developed, and chronic/regressing. The study included 35 patients. In 80% of these patients, EDHM was diagnosed after the hematologic disorder. Approximately 45% of the cohort experienced hematologic disease progression or relapse, while 65% required therapeutic intervention during the course of their hematologic disease. In total, 15/19 CLL patients had non-mutated IgHV, a marker of a more aggressive hematologic disease course. Dermatologic lesion morphology was heterogeneous, with most lesions occurring on exposed areas, and a significant 94% of patients demonstrated lesion seasonality. Histopathologic findings were consistent with features typically associated with insect bites. In addition, examination of lesions at different chronological stages revealed substantial similarities with Wells syndrome. Our findings support the potential role of insect bites in triggering EDHM in the context of adaptive immune dysfunction. EDHM may be associated with a more aggressive disease course or may be a marker of disease progression. The observed co-occurrence of features typical of Wells syndrome in EDHM patients suggests that these conditions are part of a spectrum of disorders that vary in clinical expression.
PubMed: 38792476
DOI: 10.3390/jcm13102935 -
Biomolecules Apr 2024Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a...
Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4 T cell responses in vitro and whether gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4 T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, = 0.086) compared with normal embryonic kidney cells (Hek293). CD4 T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells ( = 0.0033). Significant differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL ( = 0.0011) and relapsed/refractory ( = 0.0051) B cell ALL ( = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 ( = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.
Topics: Humans; Receptors, Tumor Necrosis Factor, Member 14; Biomarkers, Tumor; Male; Female; Prognosis; Middle Aged; Adult; CD4-Positive T-Lymphocytes; K562 Cells; HEK293 Cells; Cell Proliferation; Aged; Cell Line, Tumor; Young Adult; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38785930
DOI: 10.3390/biom14050523 -
Cancer Medicine May 2024To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia...
BACKGROUND
To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia (B-ALL) in adults.
METHODS
Between September 2010 and January 2022, adult patients with B-ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions.
RESULTS
One hundred and forty-three B-ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo-HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo-HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo-HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo-HSCT and chemotherapy groups with negative MRD after consolidation therapy.
CONCLUSIONS
B-ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long-term outcomes even without allo-HSCT. Allo-HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.
Topics: Humans; Male; Adult; Female; Hematopoietic Stem Cell Transplantation; Neoplasm, Residual; Retrospective Studies; Prognosis; Middle Aged; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Adolescent; Treatment Outcome; Transplantation, Homologous
PubMed: 38785213
DOI: 10.1002/cam4.7310 -
Choanephora infundibulifera Rhinosinusitis in Man with Acute Lymphoblastic Leukemia, Tennessee, USA.Emerging Infectious Diseases Jun 2024Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for...
Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.
Topics: Humans; Male; Tennessee; Sinusitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Mucormycosis; Mucorales; Rhinitis; Adult; Antifungal Agents; Rhinosinusitis
PubMed: 38782142
DOI: 10.3201/eid3006.230794 -
BMC Infectious Diseases May 2024Diarrhea is a common disease in immunocompromised patients and can be associated with greater morbidity and even mortality. Therefore, the present study was designed to...
AIM
Diarrhea is a common disease in immunocompromised patients and can be associated with greater morbidity and even mortality. Therefore, the present study was designed to determine the prevalence of Aeromonas spp., Campylobacter spp., and C. difficile among immunocompromised children.
METHODS
This study was conducted on 130 stool samples from patients with diarrhea who had defects in the immune system and were referred to Hazrat Masoumeh Children's Hospital in Qom. Demographic information, clinical symptoms, immune status, and duration of chemotherapy were also recorded for each child. DNAs were extracted from the stool, and then direct PCR assays were done by specific primers for the detection of Aeromonas spp., Campylobacter spp., and toxigenic C. difficile, including tcdA/B and cdtA/B genes. Co-infection in patients was also evaluated.
RESULTS
60.8% and 39.2% were male and female, respectively, with a m ± SD age of 56.72 ± 40.49 months. Most cases of immunocompromised states were related to Acute Lymphocytic Leukemia (77.7%) and Non-Hodgkin Lymphoma (14.6%). 93.1% of patients were undergoing chemotherapy during the study. Among patients, most clinical symptoms were related to bloody diarrhea (98.5%) and fever (92.3%). Based on PCR, 14.6, 9.2, and 1.5% were positive for Aeromonas spp., C. difficile, and C. jejuni, respectively. Among the C. difficile-positive cases, the tcdA gene was only detected in one patient. In total, three co-infections were identified, which included Aeromonas spp./C. difficile (tcdA), C. jejuni/C. difficile, and C. jejuni/Aeromonas spp.
CONCLUSIONS
This is the first study in Iran to investigate the simultaneous prevalence of some pathogens in immunocompromised children with diarrhea. Because Aeromonas spp., Campylobacter spp., and C. difficile are not routinely detected in some laboratories, infections caused by them are underappreciated in the clinic. Our results showed that these pathogens are present in our region and can cause gastroenteritis in children, especially those with underlying diseases. Therefore, increasing the level of hygiene in some areas and controlling bacterial diarrheal diseases should be given more attention by health officials.
Topics: Humans; Female; Immunocompromised Host; Male; Child, Preschool; Diarrhea; Child; Aeromonas; Prevalence; Clostridioides difficile; Campylobacter; Infant; Feces; Clostridium Infections; Gram-Negative Bacterial Infections; Adolescent; Campylobacter Infections; Coinfection
PubMed: 38778271
DOI: 10.1186/s12879-024-09372-3 -
Life Science Alliance Aug 2024The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21) translocation, is known to have a complex karyotype defined by a series of large-scale...
The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21) translocation, is known to have a complex karyotype defined by a series of large-scale chromosomal rearrangements. Taken from a 15-yr-old at relapse, the cell line offers a practical model for the study of pediatric B-ALL. In recent years, short- and long-read DNA and RNA sequencing have emerged as a complement to karyotyping techniques in the resolution of structural variants in an oncological context. Here, we explore the integration of long-read PacBio and Oxford Nanopore whole-genome sequencing, IsoSeq RNA sequencing, and short-read Illumina sequencing to create a detailed genomic and transcriptomic characterization of the REH cell line. Whole-genome sequencing clarified the molecular traits of disrupted ALL-associated genes including , , , , and , as well as the glucocorticoid receptor Meanwhile, transcriptome sequencing identified seven fusion genes within the genomic breakpoints. Together, our extensive whole-genome investigation makes high-quality open-source data available to the leukemia genomics community.
Topics: Humans; Cell Line, Tumor; Whole Genome Sequencing; High-Throughput Nucleotide Sequencing; Translocation, Genetic; Oncogene Proteins, Fusion; Genomics; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transcriptome; Gene Expression Profiling; Core Binding Factor Alpha 2 Subunit; Karyotyping; Sequence Analysis, RNA
PubMed: 38777370
DOI: 10.26508/lsa.202302481 -
Journal of Translational Medicine May 2024Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in...
BACKGROUND
Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application.
METHODS
We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro.
RESULTS
In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them.
CONCLUSIONS
We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.
Topics: Antigens, CD19; Animals; Humans; Receptors, Chimeric Antigen; Cell Line, Tumor; Immunotherapy, Adoptive; Drug Resistance, Neoplasm; Mice; Coculture Techniques; Xenograft Model Antitumor Assays; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38773607
DOI: 10.1186/s12967-024-05254-z