Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963-2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5-5.3) for SMNs and 10.4%(95%CI: 8.9-12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1-3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3-7.9), and without TBI (HR:4.0,95%CI: 1.2-13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4-4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors.

Patterns of the Leukemia Records that were Referred to the Regional Laboratory in Makkah, Saudi Arabia.

BACKGROUND: Leukemia is the fifth most common cancer in Saudi Arabia. The aim of this study was to assess the various patterns of leukemia associated with age, gender, and nationality in this region. METHODS: This cross-sectional study was conducted at the regional laboratory in Makkah, Saudi Arabia, from April to November 2023. Descriptive statistics were presented as frequencies and percentages by using the GraphPad Prism software. RESULTS: This study included 107 patients, and the results showed that leukemia cases were higher in males than females and more prevalent in older patients (above 50 years of age). Overall, acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were the most common types of leukemia among Saudi patients. In addition, AML was the most prevalent type of leukemia in males and females, followed by ALL. Data also revealed that ALL was the most common type in the younger population, whereas AML was highly prevalent in older patients. CONCLUSIONS: In conclusion, this study provides valuable information about the patterns of leukemia reported at the regional laboratory in Makkah and will help in designing management and preventive approaches for these patients. This epidemiological investigation is also valuable for establishing proper medical databases.

High ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia: an observational study.

BACKGROUND: High ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukaemia is the most common malignancy in children, the incidence is increasing, and in the USA disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia. METHODS: We used data from California birth records (children born from Jan 1, 1982, to Dec 31, 2015) and California Cancer Registry (those diagnosed with childhood cancer in California from Jan 1, 1988, to Dec 31, 2015) to identify acute lymphoblastic leukaemia cases diagnosed in infants and children aged 14 years and younger and controls matched by sex, race, ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. The association between ambient temperature and acute lymphoblastic leukaemia was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy), adjusted for relative humidity and particulate matter less than 2·5 microns in aerodynamic diameter, and constructed an alternatively matched dataset for exposure contrast by seasonality. FINDINGS: 6849 cases of childhood acute lymphoblastic leukaemia were identified and, of these, 6258 had sufficient data for study inclusion. We also included 307 579 matched controls. Most of the study population were male (174 693 [55·7%] of the 313 837 included in the study) and of Latino ethnicity (174 906 [55·7%]). The peak association between ambient temperature and risk of acute lymphoblastic leukaemia was observed in gestational week 8, where a 5°C increase was associated with an odds ratio of 1·07 (95% CI 1·04-1·11). A slightly larger effect was seen among Latino children (OR 1·09 [95% CI 1·04-1·14]) than non-Latino White children (OR 1·05 [1·00-1·11]). The sensitivity analyses supported the results of the main analysis. INTERPRETATION: Our findings suggest an association between high ambient temperature in early pregnancy and risk of childhood acute lymphoblastic leukaemia. Further replication and investigation of mechanistic pathways might inform mitigation strategies. FUNDING: Yale Center on Climate Change and Health, The National Center for Advancing Translational Science, National Institutes of Health.

Nutritional Status and Body Composition at Diagnosis, of South Indian Children with Acute Lymphoblastic Leukaemia (ALL).

BACKGROUND: Accurate estimation of body composition, particularly, Body Cell Mass (BCM), which is independent of hydration status is important in children with cancer. This study aimed to accurately measure the anthropometry and body composition of children with Acute Lymphoblastic Leukaemia (ALL) at diagnosis and compare them with healthy children from South India. METHODS: This was a cross-sectional study in children aged 2 to 8 y with ALL from St. John's Medical College Hospital, Bengaluru, and age and sex-matched, normal-weight children recruited as controls from communities. Anthropometry (weight, height, circumferences), skinfolds and body composition measurements using a whole-body potassium counter were performed. Body mass index-for-age, weight and height for age z-scores were calculated using WHO child growth standards. Biochemical markers, dietary intake and physical activity details were recorded. Categorical and continuous variables were analyzed by chi-square and independent t-tests respectively.     Results: The mean age of the children with ALL (n = 39) was 4.6±1.9 y and control group (n=39) was 4.7±1.9 y; 61.5% were boys. The prevalence of underweight, overweight/obesity and stunting were 17.9%, 7.7%, and 10.3% respectively. The mean weight and height, of children with ALL and children in the control group were 16.8±6.2 kg and 16.4±4.1 kg, 104.3±14.9 cm and 105.1±12.2 cm, respectively with no statistical difference. Children with ALL showed lower body cell mass index kg/m2 (4.6± 0.8), compared to children in the control group (4.7±0.9) p=0.527, but higher fat mass index kg/m2 (3.6±1.1 vs. 3.4±0.8) p=0.276. CONCLUSION: At diagnosis, anthropometric and body composition measurements were similar between children with ALL and children in the control group. The BCM showed a non-significant trend of being lower in children with ALL, which requires close monitoring during treatment. Evaluating early-stage nutritional status and body composition can help in planning appropriate interventions during treatment to prevent long term non-communicable diseases.

Coinfections and comorbidities observed in COVID-19 during the influenza season in the pediatric patient.

OBJECTIVE: To evaluate if the comorbidity and coinfections presented by SARS-CoV-2 infection vs. COVID-19 impact our Mexican children. METHOD: Prospective and observational study that included the 2020-2021 peak influenza season. All patients with a diagnosis of infection by SARS-CoV-2 vs. COVID-19 who were admitted to the Hospital Infantil de Mexico were analyzed. Real-time RT-PCR for SARS-CoV-2 was performed in all patients, determining E, RdRp and RP genes and protein N, as well as RT-PCR for detection of respiratory viruses. RESULTS: The inclusion criteria were met by 163 patients. The group with the highest risk of becoming ill was adolescents (40.4%), followed by schoolchildren and preschoolers (21.4% and 19.6% of the cases, respectively). There were three cases with viral coinfection: two (1.2%) with parvovirus B-19 and one (0.6%) with herpes type I; another two (1.2%) showed bacterial coinfection. The main comorbidity were obesity, acute lymphoblastic leukemia and arterial hypertension. Regarding mortality, we only had four cases (2.4%). CONCLUSIONS: Obesity, cancer, hypertension, heart disease and diabetes are comorbidity present in our patients, as referred to in literature, but not coinfections. In our study, we did not have any associated mortality related to comorbidity.

OBJETIVO: Evaluar el impacto de la comorbilidad y de las coinfecciones presentadas por la infección por SARS-CoV-2 vs. COVID-19 en niños mexicanos. MÉTODO: Estudio prospectivo y observacional que comprendió la temporada alta de influenza 2020-2021, analizando todos los pacientes con diagnóstico de infección vs. enfermedad por SARS-CoV-2 vs. COVID-19 que ingresaron al Hospital Infantil de México. Se realizó en todos RT-PCR en tiempo real para SARS-CoV-2, determinando gen E, gen RdRp, gen RP y proteína N, y RT-PCR multiplex para detección de virus respiratorios. RESULTADOS: Los criterios de inclusión los cumplieron 163 pacientes. El grupo con mayor riesgo de enfermar fueron los adolescentes (40.4%), seguidos de los escolares y preescolares (21.4% y 19.6% de los casos, respectivamente). Hubo tres casos con coinfección viral: dos (1.2%) con parvovirus B-19 y uno (0.6%) con herpes tipo I; hubo otros dos (1.2%) con coinfección bacteriana. La principal comorbilidad correspondió a obesidad, leucemia linfoblástica aguda e hipertensión arterial. En cuanto a mortalidad, solo hubo cuatro casos (2.4%). CONCLUSIONES: Obesidad, cáncer, hipertensión, cardiopatías y diabetes constituyen la comorbilidad en nuestros pacientes, como se refiere en la literatura, no así las coinfecciones. En nuestro estudio no hubo casos de mortalidad relacionada con la comorbilidad.

Epidemiology of acute lymphoblastic leukaemia in Sardinia, Italy: Age, sex, and environmental correlates.

Using a database of 1974-2003 incident cases of haematological malignancies, we explored the time trend, geographic spread and socio-economic and environmental correlates of ALL incidence in Sardinia, Italy, by sex and age. The age- and sex-standardized (World population) ALL incidence rate was 2.0 per 100,000 (95% CI 1.8 - 2.1) and showed variable trend patterns by sex and age. In the total population, ALL incidence showed an annual per cent change of -1.4% (95% CI -0.59 - -3.34) over the study period, with a knot separating a downward slope in 1974-1996 from an increase in 1996-2003. ALL incidence replicated such pattern in women but not men, whose incidence did not substantially vary over the study period (APC = -2.57%, 95% CI -5.45 - 0.26). Among women, the spatial analysis suggested a clustering of ALL in the southwestern part of the region, whilst only a commune had a high posterior probability of a high ALL incidence among men. Three unrelated communes showed a high posterior probability of ALL at age ≤ 24; only the most populated urban centre showed excess cases at age ≥ 25 years. There was no correlation between the geographic spread of ALL at ages ≤ 24 and ≥ 25 years (p = 0.082). Urban residence was a risk factor for the younger age group. Residences near industrial settlements and in the most populated urban centre were risk factors for subjects aged ≥ 25 years. Our findings suggest age-related differences in ALL aetiology.

Experience in improving treatment outcomes for childhood acute lymphoblastic leukemia: real-world results for a province in China, 2011-2020.

The present study aimed to investigate the real-world results of childhood acute lymphoblastic leukemia (cALL) cases in Fujian, China. The clinical data of 1414 patients with newly diagnosed cALL in Fujian were retrospectively analyzed. Patients were treated according to the Chinese Children Leukemia Group 2008 protocol (CCLG-ALL 2008 group) or Chinese Children's Cancer Group 2015 protocol (CCCG-ALL 2015 group). Cumulative incidence of treatment abandonment (TA) at 5 years was 4.2% ± 0.6% and significantly associated with treatment period and risk stratification. The 5-OS and EFS were significantly higher in the CCCG-ALL 2015 group than in the CCLG-ALL 2008 group. Patients treated with CCCG-ALL 2015 from Fujian Medical Union Hospital had a significantly higher 4-year OS and EFS than did those from the other four hospitals. Real-world TA of cALL greatly decreased, and its long-term survival significantly increased in Fujian, which may be related to optimizing programs, multi-center collaboration, and improving treatment compliance.

Association between direct acting agents used for chronic hepatitis C virus infection and the occurrence of acute leukaemia - A disproportionality analysis.

BACKGROUND AND AIMS: A recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection. METHODS: We conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls. The primary outcome was AML. Secondary outcomes were AML without MPAL, MPAL, acute lymphoid leukemia (ALL) and acute leukemia (AL, high-level term encompassing AML, ALL, MPAL and unspecified acute leukemia [UAL]). The information component (IC0.25) and proportional reporting ratio (PRR0.25) were computed to assess a potential pharmacovigilance signal. RESULTS: We identified 49 notifications reporting any AL occurrence after anti-HCV treatments from June 1997 to December 2020: 23 (47%) involved a DAA, 24 (49%) interferon and 12 (24%) ribavirin. The DAAs sofosbuvir and ledipasvir were suspected in 74% (n = 17) and 39% (n = 9) of cases. The events reported were AML (n = 22), ALL (n = 11), AML and ALL (n = 1) and UAL (n = 15) and no MPAL. DAA, interferon or ribavirin were not significantly associated with AML, ALL or AL. CONCLUSION: This study did not find any association between DAA exposure and the occurrence of AML. Nevertheless, vigilance should remain, particularly for MPAL, which may not have been well captured in our study because of its rareness and high risk of misclassification.

Impact of the COVID-19 pandemic on utilization and cost for care of pediatric and young adult ALL.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and among the most common malignancies in young adults and requires a unique pattern of healthcare utilization including an acute/emergent presentation and an intensive initial 8 months of therapy followed by two years of outpatient treatment. The COVID-19 pandemic caused massive global disruptions in healthcare use and delivery. This report aims to examine the effects of the COVID-19 pandemic on the presentation, diagnosis and continued management of childhood and young adult ALL in regard to utilization and cost of care among commercially insured individuals in the United States. RESULTS: Utilizing a commercial insurance claims database, 529 pediatric and young adult patients were identified who were diagnosed with ALL between January 2016 and March 2021. New diagnoses were evaluated by era and demographics. Utilization was measured by COVID-related era as number of inpatient and outpatient encounters, inpatient days, and cumulative cost during the initial 8 months of therapy. None of these cost or utilization factors changed significantly during or shortly after the pandemic. These findings reinforce that the necessary care for pediatric and young adult ALL was unwavering despite the massive shifts in the healthcare system caused by the COVID-19 pandemic. This provides a valuable benchmark as we further examine the factors that influence the pandemic's impact on health equity and access to care, especially in vulnerable pediatric and young adult populations. This is the first investigation of the effect of the COVID-19 pandemic on utilization and cost of care in pediatric and young adult cancer.

Epidemiological characteristics and influencing factors of acute leukemia in children and adolescents and adults: a large population-based study.

OBJECTIVE: To assess the epidemiological characteristics and prognostic factors of acute leukemia (AL) in children and adolescents, and make comparisons between pediatric and adult patients. METHODS: This retrospective cohort study enrolled AL patients from the Surveillance, Epidemiology, and End Results (SEER) 1975-2016. OS in children and adolescents and adults with AL was compared and analyzed separately by age and AL subtype. RESULTS: Totally 61,694 AL patients were identified, with 45,411 (73.6%) adults and 16,283 (26.4%) children and adolescents. From 2000 to 2016, the incidence rates of AL [annual percent changes (APC) = 1.2, 95%CI = 0.9-1.6, P < 0.05] and acute lymphoblastic leukemia (ALL) (APC = 1.5, 95%CI = 1.1-1.8, P < 0.05) in children and adolescents were significantly increasing. For adults, AL (APC = 0.9, 95%CI = 0.3-1.5, P < 0.05), ALL (APC = 2.5, 95%CI = 2.0-3.1, P < 0.05) and acute myeloid leukemia (AML) (APC = 0.9, 95%CI = 0.4-1.5, P < 0.05) had significantly elevated incidence rates. Overall survival (OS) in children and adolescents with AL was significantly higher than that in adults with AL (log-rank P < 0.0001). OS in children and adolescents and adults with ALL, AML and AUL decreased with age (all log-rank P < 0.0001). Older age, male sex and black race were risk factors for the survival of children and adolescents and adults with ALL, AML and AUL. CONCLUSION: From 2000 to 2016, the incidence rates of AL in children and adolescents and adults were increasing. Children and adolescents with AL had significantly better OS than adults with AL, and OS declined with age in both children and adolescents and adults with ALL, AML and AUL.

Feasibility and limitations of using commercial databases to evaluate residential mobility in registry-based research on childhood cancer.

BACKGROUND: Researchers have used commercial databases containing residential addresses to reduce exposure misclassification in case-control studies. Our objective is to evaluate the potential systematic bias regarding case status when reconstructing residential locations from commercial databases. METHODS: Our study population of 3640 Colorado-born children includes 520 children diagnosed with acute lymphocytic leukemia between 2002 and 2019. We aligned addresses and date ranges obtained from LexisNexis with registry dates to determine three dichotomous outcomes: Found in LexisNexis, conception date found in LexisNexis, and reference date/diagnosis date found in LexisNexis. We applied logistic regression to determine whether outcomes differed by case status. RESULTS: Mothers of cases were 39% more likely to be found in LexisNexis than mothers of controls (OR = 1.39, 95% CI: 0.97, 2). Of the mothers found in LexisNexis, a conception address was 33% more likely (OR= 1.33, 95% CI: 1.06, 1.66) and a reference/diagnosis address was 60% more likely (OR= 1.60, 95% CI: 1.21, 2.12) to be found for mothers of cases than mothers of controls. CONCLUSION: This study indicates that use of commercial databases to reconstruct residential locations may systematically bias results in case-control studies of childhood cancers.

"Characterization of residential proximity to sources of environmental carcinogens in clusters of Acute Lymphoblastic Leukemia in San Luis Potosi, Mexico".

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most prevalent neoplasia in children and teenagers in Mexico. Although epidemiological data supports that children's residence close to emissions from vehicular traffic or industrial processes increases the risk of ALL; and the IARC states that benzene, PAHs, and PM 2.5 are well-known environmental carcinogens, there is a gap in linking these carcinogenic hazards with the sources and their distribution from scenario perspective. AIM: To identify ALL clusters in the population under 19 years of age and characterize the environment at the neighborhood level by integrating information on sources of carcinogenic exposure using spatial analysis techniques in the Metropolitan Area of San Luis Potosi, Mexico. METHODS: Using the Kernel Density test, we designed an ecological study to identify ALL clusters from incident cases in the population under 19 years of age. A multicriteria analysis was conducted to characterize the risk at the community level from carcinogenic sources. A hierarchical cluster analysis was performed to characterize risk at the individual level based on carcinogenic source count within 1 km for each ALL case. RESULTS: Eight clusters of carcinogenic sources were located within the five identified ALL clusters. The multicriteria analysis showed high-risk areas (by density of carcinogenic source) within ALL clusters. CONCLUSIONS: This study has a limited source and amount of available data on ALL cases, so selection bias is present as well as the inability to rule out residual confounding factors, since covariates were not included. However, in this study, children living in environments with high vehicular density, gas stations, brick kilns, incinerators, commercial establishments burning biomass, or near industrial zones may be at higher risk for ALL.

Epidemiology and risk factors of bloodstream infections among adolescents and young adults with acute lymphoblastic leukaemia: An 11-year retrospective cohort study.

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 µmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children.

Exclusive Breastfeeding Duration and Risk of Childhood Cancers.

Importance: Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone. Objective: To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers. Design, Setting, and Participants: This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023. Exposure: Duration of exclusive breastfeeding in infancy. Main Outcomes and Measures: Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models. Results: A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to decreased risk of BCP-ALL (AHR, 0.62; 95% CI, 0.39-0.99), but not with risk of central nervous system tumors (AHR, 0.96; 95% CI, 0.51-1.88) or solid tumors (AHR, 0.87; 95% CI, 0.55-1.41). Conclusions and Relevance: In this cohort study, longer duration of exclusive breastfeeding was associated with reduced risk of childhood BCP-ALL, corroborating results of previous case-control investigations in this field. To inform future preemptive interventions, continued research should focus on the potential biologic mechanisms underlying the observed association.

Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-Hodgkin lymphoma in a US population-based dataset.

BACKGROUND: Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced. METHODS: We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables. RESULTS: There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0-3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures. CONCLUSIONS: Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication.

COVID-19 in Pediatric Patients With Acute Lymphoblastic Leukemia or Lymphoma.

Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes. Objective: To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy. Design, Setting, and Participants: This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period. Exposures: SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2. Main Outcomes and Measures: Description of the spectrum of COVID-19 illness and chemotherapy modifications. Results: Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021). Conclusions and Relevance: In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.

The burden of acute lymphoid leukemia among adolescents and young adults in the Western Pacific Region: evidence from Global Burden Disease 2019.

PURPOSE: Acute lymphoblastic leukemia (ALL) is a type of blood cancer that affects white blood cells. Here, we use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, to estimate the burden and incidence rate changes in adolescents and young adults (AYA) ALL in the Western Pacific Region and to reveal potential risk factors of incidence- and mortality rates. METHODS: The GBD 2019 study data was stratified by sex, age, country, and territory. We calculated the Estimated annual percentage changes (estimated APC) in mortality and incidence rates for each of the 25 countries and territories of the western Pacific region from 1990 to 2019. RESULTS: This study found global AYA ALL incidence rates had increased while the mortality rates had decreased between 1990 and 2019. Moreover, healthcare access and quality (HAQ), and government per capita health spending were identified as country-level risk factors of AYA ALL incidence rates, while HAQ, male education, and sex were identified as mortality rate predictors in 25 Western Pacific Region countries. CONCLUSION: To address and reduce the burden of incidence and mortality among AYA, various regions around the world, particularly developing countries, could revise their AYA prevention and treatment strategies.

Pediatric leukemia and maternal occupational exposure to anticancer drugs: the Japan Environment and Children's Study.

ABSTRACT: Occupational exposure to medical agents and ionizing radiation has been suggested as a possible risk factor for childhood cancer. However, the relationship between such exposure and pediatric malignant neoplasms has not yet been comprehensively studied. This cohort study aimed to investigate the association between parental occupational exposure to hazardous medical agents or ionizing radiation and the risk of childhood cancer in offspring. Data from a large birth cohort in Japan, which included 104 062 fetuses, were analyzed. The primary outcome was the development of leukemia or brain tumors diagnosed by community physicians during the first 3 years after birth. Exposure factors were medical agents, including anticancer agents, ionizing radiation, and anesthetics, handled by mothers during pregnancy or by fathers for 3 months before conception. The incidence of leukemia, but not of brain tumors, was higher in mothers exposed to anticancer drugs. Multivariable regression analysis showed that maternal exposure to anticancer drugs was associated with an increased risk of leukemia in offspring older than 1 year (adjusted relative risk, 7.99 [95% confidence interval, 1.98-32.3]). Detailed information obtained from medical certificates of patients with identified leukemia revealed no infant leukemia but acute lymphoblastic leukemias in the exposed group. Our findings suggest that maternal occupational exposure to anticancer drugs may be a potential risk factor for acute lymphoblastic leukemia in offspring older than 1 year. Effective prevention methods may be necessary to prevent maternal exposure to anticancer drugs and to reduce the risk of childhood malignant neoplasms.