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Cancer Epidemiology Dec 2011Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results...
BACKGROUND
Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results have been remarkably consistent, but there is still no explanation for this increase. In this study we evaluated the effect of 60 Hz magnetic fields on acute lymphocytic leukemia (ALL) in the State of São Paulo, Brazil.
METHODS
This case-control study included ALL cases (n=162) recruited from eight hospitals between January 2003 and February 2009. Controls (n=565) matched on gender, age, and city of birth were selected from the São Paulo Birth Registry. Exposure to extremely low frequency magnetic fields (ELF MF) was based on measurements inside home and distance to power lines.
RESULTS
For 24h measurements in children rooms, levels of ELF MF equal to or greater than 0.3microtesla (μT), compared to children exposed to levels below 0.1 μT showed no increased risk of ALL (odds ratio [OR] 1.09; 95% confidence interval [95% CI] 0.33-3.61). When only nighttime measurements were considered, a risk (OR 1.52; 95% CI 0.46-5.01) was observed. Children living within 200 m of power lines presented an increased risk of ALL (OR 1.67; 95% CI 0.49-5.75), compared to children living at 600 m or more of power lines. For those living within 50 m of power lines the OR was 3.57 (95% CI 0.41-31.44).
CONCLUSIONS
Even though our results are consistent with the small risks reported in other studies on ELF MF and leukemia in children, overall our results do not provide support for an association between magnetic fields and childhood leukemia, but small numbers and likely biases weaken the strength of this conclusion.
Topics: Brazil; Case-Control Studies; Child; Child, Preschool; Electromagnetic Fields; Female; Housing; Humans; Infant; Male; Odds Ratio; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 21840286
DOI: 10.1016/j.canep.2011.05.008 -
Bosnian Journal of Basic Medical... Apr 2021Childhood leukemia is cancer that seriously threatens the life of children in China. Poor sensitivity to chemotherapy and susceptibility to drug resistance are the... (Review)
Review
Childhood leukemia is cancer that seriously threatens the life of children in China. Poor sensitivity to chemotherapy and susceptibility to drug resistance are the reasons for the treatment of T-cell acute lymphocytic leukemia (T-ALL) being extremely difficult. Moreover, traditional intensive chemotherapy regimens cause great damage to children. Therefore, it is highly important to search for targeted drugs and develop a precise individualized treatment for child patients. There are activating mutations in the NOTCH1 gene in more than 50% of human T-ALLs and the Notch signaling pathway is involved in the pathogenesis of T-ALL. In this review, we summarize the progress in research on T-ALL and Notch1 signaling pathway inhibitors to provide a theoretical basis for the clinical treatment of T-ALL.
Topics: Child; Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Receptor, Notch1; Signal Transduction
PubMed: 32415821
DOI: 10.17305/bjbms.2020.4687 -
Italian Journal of Pediatrics Jun 2022Breastfeeding might prevent childhood cancer by stimulating the immune system. (Review)
Review
BACKGROUND
Breastfeeding might prevent childhood cancer by stimulating the immune system.
METHODS
The following databases, including PubMed, Embase, and Cochrane Library, were searched from inception to January 10, 2021.
RESULTS
In dose-dependent manner, there was a statistically significant inverse association between any breastfeeding and the incidence of childhood cancer. There was no evidence that breastfeeding was inversely related to childhood cancer of the skeletal, reproductive, or sensory systems. However, breastfeeding was inversely associated with the incidence of hematological malignancies and cancers of the nervous and urinary systems. Among hematological malignancies, the relationship was significant for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), but not for acute non-lymphocytic leukemia (ANLL), Hodgkin's lymphoma (HL), or non-HL.
CONCLUSIONS
The evidences demonstrated that breastfeeding have a potential protective role in preventing selective childhood cancer growth, especially for ALL, AML, cancer of nervous and urinary systems. This study recommended that breastfeeding be extended for as long as possible or maintained for at least 6 months to prevent selective childhood cancer growth.
Topics: Breast Feeding; Female; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35710389
DOI: 10.1186/s13052-022-01292-9 -
Internal Medicine (Tokyo, Japan) 2023Objective To investigate the pathogenesis of Philadelphia (Ph)-positive acute lymphocytic leukemia (ALL), we established a lymphoblastoid cell line. Methods Bone marrow...
Objective To investigate the pathogenesis of Philadelphia (Ph)-positive acute lymphocytic leukemia (ALL), we established a lymphoblastoid cell line. Methods Bone marrow cells from a patient with Ph-positive ALL were enriched by Ficoll-Hypaque centrifugation and cultured in medium with fetal calf serum. Materials The mononuclear cells of bone marrow aspirate were obtained from an adult man with ALL after he experienced relapse following induction therapy including imatinib mesylate. Results The cell line termed TNA-M was established, carrying a three-way Ph translocation involving two chromosome 9s and one chromosome 22 as a sole karyotypic abnormality. Furthermore, the cells were positive for CD13 and CD33 in addition to CD19, CD22 and CD79a antigens. Conclusion This unique cell line is expected to be a valuable tool for understanding the pathogenesis of Ph-positive ALL.
Topics: Adult; Male; Humans; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Cell Line; Imatinib Mesylate; Sialic Acid Binding Ig-like Lectin 3
PubMed: 36858620
DOI: 10.2169/internalmedicine.9359-22 -
International Journal of Molecular... Apr 2022Refractory disease and relapse remain the main causes of cancer therapy failure. Refined risk stratification, treatment regimens and improved early diagnosis and... (Review)
Review
Refractory disease and relapse remain the main causes of cancer therapy failure. Refined risk stratification, treatment regimens and improved early diagnosis and detection of minimal residual disease have increased cure rates in malignancies like childhood acute lymphoblastic leukaemia (ALL) to 90%. Nevertheless, overall survival in the context of drug resistance remains poor. The regulatory role of micro RNAs (miRNAs) in cell differentiation, homeostasis and tumorigenesis has been under extensive investigation in different cancers. There is accumulating data demonstrating the significance of miRNAs for therapy outcomes in lymphoid malignancies and some direct demonstrations of the interplay between these small molecules and drug response. Here, we summarise miRNAs' impact on chemotherapy resistance in adult and paediatric ALL and chronic lymphocytic leukaemia (CLL). The main focus of this review is on the modulation of particular signaling pathways like PI3K-AKT, transcription factors such as NF-κB, and apoptotic mediators, all of which are bona fide and pivotal elements orchestrating the survival of malignant lymphocytic cells. Finally, we discuss the attractive strategy of using mimics, antimiRs and other molecular approaches pointing at miRNAs as promising therapeutic targets. Such novel strategies to circumvent ALL and CLL resistance networks may potentially improve patients' responses and survival rates.
Topics: Adult; Child; Drug Resistance, Neoplasm; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; MicroRNAs; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Signal Transduction
PubMed: 35563051
DOI: 10.3390/ijms23094657 -
Hematology. American Society of... Dec 2022The outcome for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved, mostly based on the use of pediatric-inspired intensive...
The outcome for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved, mostly based on the use of pediatric-inspired intensive protocols. Due to increasing disease resistance and treatment-related toxicity with age, further improvements are now expected from the expanding knowledge of ALL biology, more accurate risk stratification, and the early introduction of targeted small molecules and immunotherapy. In the last decade, the rate of AYA with B-cell precursor ALL with undetermined genetic drivers ("B-other") has shrunk from 40% to fewer than 10%. The high-risk subgroup of Philadelphia-like ALL is the most frequent entity diagnosed in this age range, offering a multitude of potentially actionable targets. The timely and accurate identification of these targets remains challenging, however. Early minimal residual disease (MRD) monitoring has become a standard of care for the risk stratification and identification of patients likely to benefit from an allogeneic hematopoietic stem cell transplantation. Recently approved immunotherapies are moving frontline to eradicate MRD, to improve the outcome of high-risk patients, and, eventually, to reduce treatment burden. Comprehensive care programs dedicated to AYA with cancer aim at improving inclusion in specific clinical trials and at giving access to appropriate psychosocial support, fertility preservation, and survivorship programs.
Topics: Young Adult; Adolescent; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematopoietic Stem Cell Transplantation; Neoplasm, Residual; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Immunotherapy
PubMed: 36485092
DOI: 10.1182/hematology.2022000336 -
Blood Jan 2017Hypodiploidy <40 chromosomes is an uncommon genetic feature of acute lymphoblastic leukemia (ALL) in both children and adults. It has long been clear by cytogenetic... (Review)
Review
Hypodiploidy <40 chromosomes is an uncommon genetic feature of acute lymphoblastic leukemia (ALL) in both children and adults. It has long been clear by cytogenetic analyses, and recently confirmed by mutational profiling, that these cases may be further subdivided into 2 subtypes: near-haploid ALL with 24 to 30 chromosomes and low-hypodiploid ALL with 31 to 39 chromosomes. Both groups are associated with a very poor prognosis, and these patients are among those who could benefit most from novel treatments.
Topics: Adult; Aneuploidy; Antineoplastic Agents; Child; Child, Preschool; Female; Genotype; Haploidy; Humans; In Situ Hybridization, Fluorescence; Induction Chemotherapy; Karyotyping; Male; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Survival Analysis
PubMed: 27903530
DOI: 10.1182/blood-2016-10-743765 -
Oncology (Williston Park, N.Y.) Apr 2011Survival in acute lymphoblastic leukemia (ALL) has improved in recent decades due to recognition of the biologic heterogeneity of ALL, utilization of risk-adapted... (Review)
Review
Survival in acute lymphoblastic leukemia (ALL) has improved in recent decades due to recognition of the biologic heterogeneity of ALL, utilization of risk-adapted therapy, and development of protocols that include optimized chemotherapy combinations, effective central nervous system (CNS) prophylaxis, post-induction intensification of therapy, and a prolonged maintenance phase of treatment. Recent molecular studies have yielded novel insights into both leukemia biology and host pharmacogenetic factors; also, large cooperative group clinical research studies have successively refined effective treatment strategies. While children have higher remission and cure rates than adults, both populations have benefited from these discoveries and innovations. Future challenges in this field include improving outcomes for high-risk patients and those with relapsed disease, and developing and integrating novel targeted therapeutic agents into current regimens to reduce toxicities while further improving outcomes.
Topics: Clinical Trials as Topic; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Risk Factors
PubMed: 21618954
DOI: No ID Found -
Journal of B.U.ON. : Official Journal... 2021To explore the efficacy of chimeric antigen receptor (CAR)-T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia (B-ALL) and the...
PURPOSE
To explore the efficacy of chimeric antigen receptor (CAR)-T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia (B-ALL) and the influencing factors for their prognosis.
METHODS
A retrospective analysis was performed on the clinical data of 46 children with relapsed or refractory B-ALL, who were admitted to and treated in our hospital from January 2015 to October 2017, and the remission and post-infusion adverse reactions were observed in all the patients. Besides, the survival of the patients was followed up and recorded, and the influencing factors for the prognosis were identified by univariate and multivariate Cox regression analyses.
RESULTS
Bone marrows were routinely monitored after infusion of CAR-T cells. It was found that 35 children patients achieved morphologic complete remission, had a lower level of minimal residual disease (MRD) than that before treatment and exhibited a response rate of 76.1%, of whom there were 33 cases of MRD-negative remission. Different degrees of cytokine release syndrome (CRS) occurred in 41 out of 46 children, consisting of 37 (80.4%) cases of grade I-II CRS and 4 (8.7%) cases of grade III-IV CRS. The concentrations of serum interleukin (IL)-6, interferon-γ (IFN-γ), ferritin and C-reactive protein (CRP) obviously rose during CRS, and their peak values in the patients with grade III-IV CRS were notably higher than those in grade I-II CRS patients (p<0.001). At the end of follow-up, the median follow-up time was 28.2 months, and the 3-year overall survival (OS) and event-free survival (EFS) rates were 28.3% and 13.0%, respectively. The results also showed that tumor burden ≥5% prior to CAR-T cell therapy [hazard ratio (HR) =3.496, 95% confidence interval (CI) =1.448-9.891, p=0.014] and non-combination with hematopoietic stem cell transplant (HSCT) therapy (HR =0.890, 95% CI =0.543-0.904, p=0.025) were independent risk factors for the prognosis of the patients.
CONCLUSIONS
Anti-cluster of classification (CD) 19 CAR-T cell therapy is safe and efficacious against relapsed or refractory B-ALL in children. Reducing the tumor burden before infusion of CAR-T cells and combined with HSCT after infusion are independent factors for improving the prognosis of the patients.
Topics: Antigens, CD19; B-Lymphocytes; Child; Female; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Receptors, Chimeric Antigen; Retrospective Studies; Survival Analysis
PubMed: 33721447
DOI: No ID Found -
The Lancet. Haematology Jul 20215-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free... (Review)
Review
5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.
Topics: Antineoplastic Agents; Blindness; Child; Hearing Loss; Hematologic Diseases; Humans; Physicians; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Renal Insufficiency
PubMed: 34171282
DOI: 10.1016/S2352-3026(21)00136-8