Childhood Leukemia Research Articles

Oral Manifestations: A Warning-Sign in Children with Hematological Disease Acute Lymphocytic Leukemia.

Acute lymphocytic leukemia (ALL) is the most frequent form of all childhood leukemias, mostly affecting children between 2 and 4 years old. Oral symptoms, such as mouth ulcers, mucositis, xerostomia, Herpes or Candidiasis, gingival enlargement and bleeding, petechiae, erythema, mucosal pallor and atrophic glossitis, are very common symptoms of ALL and can be early signs of the disease. Secondary and tertiary complications, a direct effect of chemo and radiotherapy, are associated with more severe bleeding, higher susceptibility to infections, ulcerations, inflammation of the mucous membranes, osteoradionecrosis, xerostomia, taste alterations, trismus, carious lesions and dental abnormalities. Immunotherapy, though less toxic, causes oral dysesthesia and pain. Overall, the effects in the oral cavity are transient but there are long-term consequences like caries, periodontal disease and tooth loss that impair endodontic and orthodontic treatments. Also, dental abnormalities resulting from disturbed odontogenesis are known to affect a child's quality of life. The medical dentist should identify these complications and perform appropriate oral care in tandem with other health professionals. Thus, poor oral hygiene can lead to systemic ALL complications. The aim of this review is to describe the oral complications in children with ALL who are undergoing chemo, radio or immunotherapy.

Pesticides as a potential independent childhood leukemia risk factor and as a potential confounder for electromagnetic fields exposure

BackgroundBoth pesticides and high magnetic fields are suspected to be childhood leukemia risk factors. Pesticides are utilized at commercial plant nurseries, which sometimes occupy the areas underneath high-voltage powerlines. ObjectivesTo evaluate whether potential pesticide exposures (intended use, chemical class, active ingredient) utilized at plant nurseries act as an independent childhood leukemia risk factor or as a confounder for proximity to, or magnetic fields exposure from, high-voltage powerlines. MethodsWe conducted a state-wide records-based case-control study for California with 5788 childhood leukemia cases and 5788 controls that examined specific pesticide use, magnetic field exposures and distances to both powerlines and plant nurseries. Exposure assessment incorporated geographic information systems, aerial satellite images, and other historical information. ResultsChildhood leukemia risk was potentially elevated for several active pesticide ingredients: permethrin (odds ratio (OR) 1.49, 95% confidence interval (CI) (0.83–2.67), chlorpyrifos (OR 1.29, 95% CI 0.89–1.87), dimethoate (OR 1.79, 95% CI 0.85–3.76), mancozeb (OR 1.41, 95% CI 0.85–2.33), oxyfluorfen (OR 1.41, 95% CI 0.75–2.66), oryzalin (OR 1.60, 95% CI 0.97–2.63), and pendimethalin (OR 1.82, 95% CI 0.81–2.25). Rodenticide (OR 1.42, 95% CI 0.78–2.56) and molluscicide (OR 1.22, 95% CI 0.82–1.81) exposure also presented potentially elevated childhood leukemia risks. Childhood leukemia associations with calculated fields or powerline proximity did not materially change after adjusting for pesticide exposure. Childhood leukemia risks with powerline proximity remained similar when pesticide exposures were excluded. DiscussionPesticide exposure may be an independent childhood leukemia risk factor. Childhood leukemia risks for powerline proximity and magnetic fields exposure were not explained by pesticide exposure.

Risk factors associated with paediatric leukemia – a preliminary study amongst parents

Background: Acute lymphoblastic leukemia (ALL) is the most common leukemia seen among pediatric patients. Exposure to agents such as pesticides, tobacco smoke, solvents, and air pollution associated with traffic, factories, and incinerators is consistently associated with an increased risk of developing childhood leukemia. The purpose of this article is to attempt to assess the knowledge of parents of oncology patients about possible risk factors for the development of ALL acute lymphoblastic leukemia and the need for educational campaigns to increase cancer awareness in the community.
 Material and methods: For the study, the authors created a structured questionnaire that included 15 questions. The printed questionnaire was then distributed to parents staying with their children in the pediatric oncology and hematology department and the hematology-oncology outpatient clinic at 2 clinical hospitals in Poland. The survey was conducted from February to May 2023.
 Results: The study group was formed by 256 people. 13% of respondents believe that breastfeeding increases a child's risk of leukemia. One in three questioned pointed to vaccinations as a possible trigger for cancer. The majority of respondents consider care facilities such as the nursery as exposure to the development of leukemia. The vast majority of respondents are dissatisfied with their knowledge of proliferative diseases.
 Conclusions: The overall level of parents' knowledge of leukemia risk factors is inadequate. A large percentage of respondents indicate vaccination as a risk factor for the development of ALL There is a need for educational campaigns on childhood cancer. There is a need to verify the sources of medical knowledge used by patients, especially on the Internet.

Sexual Problems as Late Effects: Awareness and Information Needs Among 1870 Long-term Norwegian Childhood, Adolescent, and Young Adult Cancer Survivors (The NOR-CAYACS Study).

Purpose: Treatment-related sexual problems are common, but understudied, among survivors of Childhood, Adolescent, and Young Adult Cancer Survivors (CAYACS). We investigated awareness of, and information needs regarding, sexual problems as late effects in a nation-wide sample of long-term CAYACS. Methods: Five-year survivors were identified by the Cancer Registry of Norway, diagnosed between 1985 and 2009 with any childhood cancer (0-18 years of age, excluding central nervous system tumors), leukemia, colorectal cancer, breast cancer, non-Hodgkin lymphoma, or malignant melanoma (19-39 years of age). Malignant melanoma survivors treated with local surgery only served as an unmatched reference group. Survivors were mailed a survey, including items on awareness and information needs. Descriptive statistics and logistic regression analyses were used for data analyses. Results: Of 5361 CAYACS invited, 2104 responded (39%), of which 1870 were eligible for inclusion. In all, 62% were aware of sexual problems as late effects (46% aware only, 16% experienced it) and 31% reported information needs. Of all groups, childhood cancer survivors reported the lowest level of awareness (43% aware, 7% experienced it) and the highest information needs (38%). In multivariable models, awareness was associated with higher education, shorter time since treatment, more intense treatments, and experiencing hormonal changes and reduced fertility. Information needs were associated with having experienced sexual problems, female gender, higher treatment intensity, chronic fatigue, and increased depressive symptoms. Conclusions: A substantial proportion of long-term CAYACS report being unaware of, and have information needs regarding sexual problems as late effects decades beyond treatment. Addressing such issues during follow-up care is important.

Unveiling the Rarity: Chronic Myeloid Leukaemia in Children and Adults: A Comparative Analysis

Unveiling the Rarity: Chronic Myeloid Leukaemia in Children and Adults: A Comparative Analysis

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Rearrangement of KMT2A Characterizes a Subset of Pediatric Parotid Mucoepidermoid Carcinomas Arising Metachronous to Acute Lymphoblastic Leukemia

Introduction: Metachronous mucoepidermoid carcinomas (MMEC) may occur in association with childhood leukemias and lymphomas. We compared molecular abnormalities of MMEC in patients with ALL with the abnormalities found in primary mucoepidermoid carcinomas (MECs) in pediatric cases and young adults. Materials and methods: Immunohistochemical stains for p63 and SOX10, molecular alterations in MAML2 and KMT2A genes detected by FISH and/or next-generation sequencing were studied in 12 pediatric MMECs secondary to ALL and six primary MECs in pediatric patients and young adults. Follow-up information of patients in both groups was obtained. Results: KMT2A rearrangements were detected in pediatric MMECs, and they were associated with remarkable histomorphological changes, including deposits of abundant stromal collagen and intratumoral lymphoid proliferations. No KMT2A rearrangements were found in primary MECs. The prognosis of MMEC in patients with ALL, especially in KMT2A-rearranged cases, was worse than in primary MECs. Kruskal-Wallis test showed a statistically significant difference in overall survival between KMT2A-rearranged MMECs and KMT2A-intact MMECs in cases with ALL (p = 0.027). Conclusion: KMT2A-rearranged MMECs in ALL patients may have inherently more aggressive behavior, even when the histomorphology of MMEC suggests a low-grade malignancy.

Evaluación de la función diastólica mediante strain de la aurícula izquierda en largos supervivientes de leucemia linfoblástica aguda infantil

Introduction and objectivesSurvivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to exposure to cardiotoxic treatment. Although assessment of diastolic function is challenging in this relatively young population, left atrial strain might provide a novel insight in this evaluation. Our aim was to examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia by using left atrial strain and conventional echocardiographic parameters. MethodsLong-term survivors who were diagnosed at a single center between 1985 and 2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and atrial strain were compared, and the latter was measured during the 3 atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups. ResultsWe analyzed 90 survivors (age, 24.6±9.7 years, time since diagnosis 18 [11-26] years) and 58 controls. PALS and LACS were significantly reduced compared with the control group: 46.4±11.2 vs 52.1±11.7; P=.003 and 32.5±8.8 vs 38.2±9.3; P=.003, respectively. Conventional diastolic parameters and PACS were similar between the groups. The reductions in PALS and LACS were associated with exposure to cardiotoxic treatment in age- and sex-adjusted analysis (≥ moderate risk, low risk, controls): 45.4±10.5, 49.5±12.9, 52.1±11.7; Padj=.003, and 31.7±9.0, 35.2±7.5, 38.2±9.3; Padj=.001, respectively. ConclusionsLong-term childhood leukemia survivors showed a subtle impairment of diastolic function that was detected with atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher exposure to cardiotoxic treatment.

Biochemical and Hematologic Profiles in B-Cell Acute Lymphoblastic Leukemia Children.

B-cell acute lymphoblastic leukemia is the most common type of leukemia found in children. Timely diagnosis, white blood cell count, age of onset, and sex are considered the most important prognostic factors in childhood leukemia. Hematological and biochemical profiles are crucially important to infer the health of leukemia patient pre-chemotherapy and post-chemotherapy treatment. In the current study 200 cases were taken and evaluated for hematological (complete blood count and white blood differential count) and biochemical parameters (renal function tests, liver function tests, serum electrolytes and serum proteins) by comparison with normal reference values. Most of the cases were male under 5 years of age. Hematology parameters including red blood cells, hemoglobin and platelet levels were relatively low whereas white blood cells level was high in cases as compared with normal reference value. Sex-wise and age-wise comparison of biochemical profile showed significant difference among B-cell acute lymphoblastic leukemia cases whereas hematological profile did not show any visible difference.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6months and in meta-analyses. Our data suggest that breastfeeding does not protect against CBT.

Outcome of hematopoietic stem cell transplantation in pediatric patients with acute lymphoblastic leukemia not in remission enrolled in JACLS ALL-02.

Hematopoietic stem cell transplantation (HSCT) is only indicated for acute lymphoblastic leukemia (ALL) patients for whom other treatments are unlikely to be curative. However, outcomes of patients not in complete remission (CR) at HSCT remain very poor. To improve the outcomes of patients receiving HSCT, it is important to obtain detailed clinical information about patients with ALL receiving HSCT in CR and not in CR. Patients enrolled in the Japan Association of Childhood Leukemia Study ALL-02 who underwent HSCT and were not in CR (non-CR patients, n = 55) were examined. The 1-year overall survival (OS) rate of non-CR patients was 27.3%. Compared with CR patients, non-CR patients experienced very early and early relapse significantly more frequently and had poorer prognostic factors. Most interestingly, high hyperdiploid (HHD) patients showed an excellent 1-year OS of 80%. In addition, long-term survival among surviving HHD patients was longer than 5years. All eight patients who survived after undergoing HSCT while not in CR were younger than 10years at initial diagnosis and were negative for central nervous system involvement. While limited, these results suggest that a subset of patients may benefit from HSCT while not in CR.

Role of breastfeeding on maternal and childhood cancers: An umbrella review of meta-analyses.

Multiple studies and meta-analyses have claimed that breastfeeding is inversely correlated with maternal and childhood cancers. These results could either be causal or confounded by shared risk factors. By conducting an umbrella review, we aimed to consolidate the relationship between breastfeeding and maternal and childhood cancers. We searched PubMed, Embase, Web of Science, Elsevier ScienceDirect, and Cochrane Library databases from inception to December 2022. Two reviewers independently extracted the data and assessed the quality of the studies using standardised forms. We considered two types of breastfeeding comparisons ("ever" vs "never" breastfeeding; and "longest" vs "shortest" duration). We estimated the pooled risk and 95% confidence interval (CI) for each meta-analysis. We included seventeen meta-analyses with 55 comparisons. There was an inverse correlation between breastfeeding and childhood leukaemia (pooled risk = 0.90, 95% CI = 0.81-0.99), neuroblastoma (pooled risk = 0.81, 95% CI = 0.71-0.93), maternal ovarian cancer (pooled risk = 0.76, CI = 0.71-0.81), breast cancer (pooled risk = 0.85, 95% CI = 0.82-0.88), and oesophageal cancer (pooled risk = 0.67, 95% CI = 0.54-0.81) for "ever" vs "never" breastfeeding; and with childhood leukaemia (pooled risk = 0.94, 95% CI = 0.89-0.98), and maternal ovarian cancer (pooled risk = 0.84, 95% CI = 0.78-0.90) and breast cancer (pooled risk = 0.92, 95% CI = 0.89-0.96) for "longest" vs "shortest" breastfeeding duration. We found evidence that breastfeeding may reduce the risk of maternal breast cancer, ovarian cancers, and childhood leukaemia, suggesting positive implications for influencing women's decision in breastfeeding. PROSPERO (CRD42021255608).

Identifying childhood leukemia with an excess of hematological malignancies in first-degree relatives in Brazil.

Familial aggregation in childhood leukemia is associated with epidemiological and genomic factors. Albeit epidemiological studies on the familial history of hematological malignancies (FHHMs) are scarce, genome-wide studies have identified inherited gene variants associated with leukemia risk. We revisited a dataset of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients to explore the familial aggregation of malignancies among their relatives. A series of 5,878 childhood leukemia (≤21 years of age) from the EMiLI study (2000-2019) were assessed. Lack of well-documented familial history of cancer (FHC) and 670 cases associated with genetic phenotypic syndromes were excluded. Leukemia subtypes were established according to World Health Organization recommendations. Logistic regression-derived odds ratios (ORs) and 95% confidence intervals (CIs) were performed and adjusted by age as a continuous variable, where ALL was the reference group for AML and conversely. The pedigree of 18 families with excess hematological malignancy was constructed. FHC was identified in 472 of 3,618 eligible cases (13%). Ninety-six of the 472 patients (20.3%) had an occurrence of FHHMs among relatives. Overall, FHC was significantly associated with AML (OR, 1.36; 95% CI, 1.01-1.82; p = 0.040). Regarding the first-degree relatives, the OR, 2.92 95% CI,1.57-5.42 and the adjOR, 1.16 (1.03-1.30; p0.001) were found for FHC and FHHM, respectively. Our findings confirmed that AML subtypes presented a significant association with hematological malignancies in first-degree relatives. Genomic studies are needed to identify germline mutations that significantly increase the risk of developing myeloid malignancies in Brazil.

Incidence and Outcome of Childhood Acute Leukemia in A Tertiary Care Hospital of Bangladesh Armed Forces

Background: Worldwide cancer is the second leading cause of death in children under 15 years and acute leukemia is the most prevalent cancer among children.
 Objective: The objective of the study was to analyze the incidence and overall outcome of childhood leukemia patients aged 0-12 years in Combined Military Hospital (CMH), Dhaka.
 Methods: It was a retrospective cross-sectional study. Children below 12 years of age with confirmed diagnosis of leukemia and received treatment from the paediatric oncology unit of department of paediatrics of CMH, Dhaka were taken for this study. Data has been collected from Hospital based cancer registry records from 2011 to 2021. There present status has been collected from regular OPD or by phone calls.
 Results: The commonest cancer was found Acute Leukemia (52%), among them Acute Lymphoblastic Leukemia (ALL) 83.15% and Acute Myeloid Leukemia (AML) 16.85%. Morphological (FAB classification) sub-divisions revealed ALL-L2 (31%) was the commonest group for ALL. In case of AML, AML-M3 (APML) was the commonest (27%). Immunophenotyping of cells revealed Pre-B ALL was the commonest. Cytogenetic analysis revealed ETV6-RUNX1 (21%), t(1;19) ((q23,p13) E2A/PBX1 (11%) were two most common genetic abnormalities found in ALL and t(15;17) (q22;q12) M3,M3v PML-RARA was the commonest cytogenetic abnormalities and (8;21) (q22;q22) RUNX1/RUNX1T1 for AML. In case of ALL overall survival was 54% and in case of AML 40%. About 10% of patients reported relapses.
 Conclusion: Incidence of acute leukemia was the highest among all childhood cancer. At the end of the study, overall survival was 52% of cases, and relapses were seen in 10% of cases.
 DS (Child) H J 2021; 38(1): 17-26

Fostering a Positive Breastfeeding Environment for the Urologic Resident

As more female trainees enter the workforce, 1 Nam C.S. Daignault-Newton S. Herrel L.A. Kraft K.H. The Future is Female: Urology Workforce Projection From 2020 to 2060. Urology. 2021; 150: 30-34https://doi.org/10.1016/j.urology.2020.08.043 Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar more urologic residents are likely to become breastfeeding mothers during their training. Breastfeeding has been shown to lower maternal incidence of hypertension, type 2 diabetes, and ovarian cancer. 2 Meek J.Y. Noble L. Section on Breastfeeding. Policy Statement: Breastfeeding and the Use of Human Milk. Pediatrics. 2022; 150e2022057988https://doi.org/10.1542/peds.2022-057988 Crossref Scopus (92) Google Scholar Additionally, children who are breastfed have lower incidences of several pediatric disorders including: sudden infant death syndrome (SIDS), childhood obesity, and childhood leukemia among others. 2 Meek J.Y. Noble L. Section on Breastfeeding. Policy Statement: Breastfeeding and the Use of Human Milk. Pediatrics. 2022; 150e2022057988https://doi.org/10.1542/peds.2022-057988 Crossref Scopus (92) Google Scholar The American Association of Pediatrics (AAP) recently released recommendations acknowledging the health advantages of continued breastfeeding beyond two years of age. These recommendations include exclusive breastfeeding for 6 months, with breastfeeding duration for greater than two years “as mutually desired”.

Estimation of the general population and children under five years of age in France exposed to magnetic field from high or very high voltage power line using geographic information system and extrapolated field data

BackgroundThe effects of extremely low-frequency magnetic fields, especially their long-term health effects, including childhood leukaemia, remain elusive. The International Agency for Research on Cancer has classified the exposure to magnetic fields >0.4 μT as ‘possibly carcinogenic to humans (group 2 B)’ for childhood leukaemia. However, the number of exposed individuals, particularly children, remains poorly documented in international literature. The objective of this study was to estimate the number of individuals living near a high or very high voltage line in France (≥63 kV), among the general population and children under the age of five years. MethodsThe estimate considered different exposure scenarios depending on the line voltage and the distance of the housing from it, and whether the line is overhead or underground. The exposure scenarios were obtained using a multilevel linear model created from a measurement database published by “Réseau de transport d'électricité”, the operator of the French electricity transmission network. ResultsBetween 0.11% (n = 67,893) and 1.01% (n = 647,569) of the French population and between 0.10% (n = 4712) and 1.03% (n = 46,950) of children under five years of age were estimated to be living in an area potentially exposed to a magnetic field, depending on the exposure scenario (>0.4 μT and >0.1 μT, respectively). ConclusionsBy making it possible to estimate the total number of residents, schools, and health institutions near high-voltage power lines, the proposed methodology can help identify potential co-exposures near high-voltage power lines, which are regularly cited as a possible explanation for contradictory results from epidemiological studies.

Partitioning for Easy Multiplexing: A Versatile Droplet PCR Application for Clone Monitoring in Tumors

Clinical genome-wide next-generation sequencing (NGS) has brought new challenges to genetic laboratories. The identification of numerous patient-specific variants that may require to be screened for on multiple other samples poses an issue when striving for time and cost-effectiveness. Here, we propose d-multiSeq, a straightforward method utilizing the advantages of droplet PCR for multiplexing combined with amplicon-based NGS. By comparing d-multiSeq with a standard multiplex amplicon-based NGS, it was shown that partitioning prevents the amplification competition seen when multiplexing and leads to a homogeneous representation of each target in the total read count for up to a 40-target multiplex without the need for prior adjustment. Variant allele frequency was reliably evaluated with a sensitivity of 97.6% for variant allele frequency up to 1%. The applicability of d-multiSeq was also tested on cell-free DNA with the successful amplification of an eight-target multiplex panel. Preliminary application of the technique to assess the clonal evolution in a childhood leukemia harboring high interpatient variability in its somatic variants is shown. d-multiSeq represents a turnkey solution for analyzing large sets of patient-specific variants on low DNA amounts and cell-free DNA.

Hyperleukocytosis in Childhood Acute Leukemia: Early Complications and Survival Outcomes

Hyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of childhood leukemia patients with hyperleukocytosis. The medical records of 690 children newly diagnosed with acute leukemia between January 1998 and December 2017 were retrospectively reviewed. The Kaplan–Meier method and log-rank test were used to assess and compare the survival outcomes. Multivariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. We found that 16.6% of 483 childhood acute lymphoblastic leukemia (ALL) patients and 20.3% of 207 childhood acute myeloid leukemia (AML) patients had hyperleukocytosis at diagnosis. ALL patients with hyperleukocytosis had more early complications than those without hyperleukocytosis (p < 0.05). Among the ALL group, the 5-year overall survival rate for those with hyperleukocytosis was significantly lower than for those without hyperleukocytosis (37.2% vs. 67.8%, p < 0.0001), while the difference was not statistically significant in the AML group (19.0% vs. 30.2%, respectively, p = 0.26). Hyperleukocytosis (hazard ratio [HR]: 2.04), extreme hyperleukocytosis (HR: 2.71), age less than 1 year (HR: 3.05), age greater than 10 years (HR: 1.64), and male sex (HR: 1.37) were independently associated with poorer overall survival in childhood ALL patients. Extreme hyperleukocytosis (HR: 2.63) and age less than 1 year (HR: 1.82) were independently associated with poorer overall survival in AML patients. Hyperleukocytosis was associated with adverse survival outcomes in childhood leukemia.

Residential exposure to magnetic fields from high-voltage power lines and risk of childhood leukemia

BackgroundSeveral studies have suggested an excess risk of leukemia among children living close to high-voltage power lines and exposed to magnetic fields. However, not all studies have yielded consistent results, and many studies may have been susceptible to confounding and exposure misclassification. MethodsWe conducted a case-control study to investigate the risk of leukemia associated with magnetic field exposure from high-voltage power lines. Eligible participants were children aged 0–15 years residing in the Northern Italian provinces of Modena and Reggio Emilia. We included all 182 registry-identified childhood leukemia cases diagnosed in 1998–2019, and 726 age-, sex- and province-matched population controls. We assessed exposure by calculating distance from house to nearest power line and magnetic field intensity modelling at the subjects’ residence. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders (distance from nearest petrol station and fuel supply within the 1000 m-buffer, traffic-related particulate and benzene concentrations, presence of indoor transformers, percentage of urban area and arable crops). ResultsIn multivariable analyses, the OR comparing children living <100 m from high-voltage power-lines with children living ≥400 m from power-lines was 2.0 (95% CI 0.8–5.0). Results did not differ substantially by age at disease diagnosis, disease subtype, or when exposure was based on modeled magnetic field intensity, though estimates were imprecise. Spline regression analysis showed an excess risk for both overall leukemia and acute lymphoblastic leukemia among children with residential distances <100 m from power lines, with a monotonic inverse association below this cutpoint. ConclusionsIn this Italian population, close proximity to high-voltage power lines was associated with an excess risk of childhood leukemia.

6-Mercaptopurine potently inhibits recruitment of SHP2 by phosphorylated PD-1 to inhibit PD-1 signalling and enhance T cell function.

Antibody inhibitors that block PD-1/PD-L1 interaction have been approved for oncological clinics, yielding impressive treatment effects. Small molecules inhibiting PD-1 signalling are at various stages of development, given that small molecular drugs are expected to outperform protein drugs in several ways. Currently, a significant portion of these small molecular inhibitors achieve this purpose by binding to a limited region of the PD-L1 protein, thereby limiting the choice of chemical structures. Alternative strategies for developing small-molecular PD-1 inhibitors are urgently needed to broaden the choice of chemical structures. Here, we report that 6-mercaptopurine (6-MP) inhibits PD-1 signalling, activates T cell function in vitro and in vivo and shrinks tumours by activating cytotoxic T cells. Mechanistically, 6-MP potently inhibited PD-1 signalling by blocking the recruitment of SHP2 by PD-1. Considering that 6-MP is a chemotherapeutic agent already approved by the FDA for childhood leukaemia, our work revealed a novel anti-tumour mechanism for this drug and suggests that 6-MP warrants further clinical evaluation for other tumour types.