Childhood Leukemia Research Articles

Spatio-temporal quasi-experimental methods for rare disease outcomes: the impact of reformulated gasoline on childhood haematologic cancer

Abstract Although some pollutants emitted in vehicle exhaust, such as benzene, are known to cause leukaemia in adults with high exposure levels, less is known about the relationship between traffic-related air pollution (TRAP) and childhood haematologic cancer. In the 1990s, the US EPA enacted the reformulated gasoline program in select areas of the U.S., which drastically reduced ambient TRAP in affected areas. This created an ideal quasi-experiment to study the effects of TRAP on childhood haematologic cancers. However, existing methods for quasi-experimental analyses can perform poorly when outcomes are rare and unstable, as with childhood cancer incidence. We develop Bayesian spatio-temporal matrix completion methods to conduct causal inference in quasi-experimental settings with rare outcomes. Selective information sharing across space and time enables stable estimation, and the Bayesian approach facilitates uncertainty quantification. We evaluate the methods through simulations and apply them to estimate the causal effects of TRAP on childhood leukaemia and lymphoma.

The Association between Allergies and Hematologic Tumors — A Review

Introduction: Dysfunctions of the immune system in allergic diseases and hematological malignancies are the subject of many studies due to the mechanisms that link them. Chronic inflammation created in the immune response in an allergic reaction has been associated with developing neoplastic diseases. Aim of the study: This review examines the potential correlation between Allergies and Hematologic Tumors: acute lymphoblastic leukemia, childhood leukemias, non-Hodgkin and Hodgkin lymphomas. Material and methods: An English-language literature review was conducted, analyzing studies from the PubMed database up to October 2024 regarding the correlation between Allergies and Hematologic Tumors. The review was performed using the PubMed database, with 50 works used. Conclusions: The relationship between allergies and hematological tumors is unclear. According to some studies, this relationship does not exist; some state, however, that allergic diseases show correlations with hematological malignancies. The results of these studies do not provide a clear answer to whether this is a positive or negative relationship. Some studies suggest that allergies reduce the risk of hematological malignancies, while others contradict this, suggesting that allergies may increase the risk of hematological tumors. The results of studies showing an increased risk of hematological malignancies in people suffering from allergies can be due to the hypothesis of antigenic stimulation, which may explain the mechanism of correlation between those diseases. This hypothesis suggests that chronic immune stimulation predisposes to hematologic malignancies such as multiple myeloma, non-Hodgkin's lymphoma (NHL), and leukemia by promoting the development of randomly occurring pro-oncogenic mutations in actively dividing immune cells. Different results on this potential correlation showed that further studies are necessary.

Maternal illnesses during pregnancy and the risk of childhood cancer: A medical-record based analysis (UKCCS).

Often relying on mother's recollections of past events, the possible relationship between maternal illness in pregnancy and risk of malignancy in their offspring has long been a focus of research. Free from recall bias, this study of childhood cancer (0-14 years) examined these associations using data abstracted from mothers' primary-care (1623 cases, 2521 controls) and obstetric (2721 cases, 5169 controls) records. Maternal infections and other illnesses in pregnancy were examined for any possible associations with childhood leukaemia, lymphoma, CNS or embryonal tumours using pooled information from the two medical record sources (2885 cases and 5499 controls), accounting for potential confounders. Maternal anaemia was associated with childhood acute myeloid leukaemia (AML) (odds ratio, OR = 2.07, 95%CI [1.40-3.08]). Anaemia during pregnancy was also recorded more frequently in the notes of mothers of children with medulloblastoma, retinoblastoma and embryonal rhabdomyosarcoma: ORs 2.36 [1.36-4.11], 1.83 [1.01-3.33] and 2.91 [1.64-5.16] respectively. Other associations included urinary tract infections (UTIs) and non-Hodgkin lymphoma (NHL); preeclampsia and NHL; and polyhydramnios with both AML and NHL. No evidence was found to suggest that influenza during pregnancy impacted on childhood leukaemia risk. In conclusion, our findings are supportive of an association between maternal anaemia in pregnancy and childhood AML, and maternal anaemia and embryonal tumours; underscoring the need for further research exploring the potential causes and roles of iron and vitamin deficiencies. Due to small numbers and lack of corroborative evidence, the associations observed for UTIs, preeclampsia, and polyhydramnios must be treated cautiously.

Pioneering sustainable treatment delivery in childhood leukemia through synchronous telemedicine-A pilot study.

Cancer care places a heavy economic burden on families and health systems, driven by high treatment costs, lengthy hospital stays, and the necessity for extensive travel to specialized facilities. To address this challenge, an integrated health care network (IHCN) was implemented for maintenance treatment in acute leukemia. The IHCN encompassed outpatient services provided by local physicians and synchronous telemedicine consultation with pediatric oncologists. This study included twenty-two pediatric patients (eleven [50.0%] females; twenty [90.9%] with B-ALL and two [9.1%] with AML). The IHCN was offered to all rural patients (n = 17) with a one-way driving distance more than 30 km, while urban patients (n = 5) received regular cancer care. Throughout the study, rural patients had a total of 510 routine clinical visits, with 367 (72%) conducted through the IHCN. Physical examinations revealed similar frequency of new abnormal findings for urban and rural patients (22.4% vs. 17.8%; p = .31). Laboratory tests indicated no significant difference in the frequency of abnormal values for various parameters between both groups. Similarly, there was no discrepancy of drug modifications or interruption in maintenance therapy between the two settings (p = .85). Moreover, patients' health-related quality of life remained within the normative range, and user satisfaction with the IHCN was notably high. The implementation of the IHCN resulted in savings of 70,158 km, 950 h of travel, and 12,277 kg CO2 emissions. This pilot study underscores the efficacy of a telemedicine-based IHCN, ensuring safety, quality of care, cost reduction, and satisfaction for both families and health care providers in pediatric leukemia management.

OA28 Case report: chronic myeloid leukemia in childhood

OA28 Case report: chronic myeloid leukemia in childhood

Precision Medicine for Acute Lymphoblastic Leukemia in Children: A Review

The clinical outcome for children diagnosed with acute lymphoblastic leukemia is a testimony to the success of modern medicine. Over the past few decades, survival has climbed from ∼10% to >90% for certain subgroups. Yet, the outcome for those with relapsed disease is often poor, and survivors struggle with a multitude of healthcare issues, some of which are lifelong. In recent years, the advent of the widespread sequencing of tumors has made available patients with previously unrecognized subtypes of leukemia, who have the potential to benefit from the addition of targeted therapies. Indeed, the promise of precision medicine, encompassing a person’s environment, genetics and lifestyle, is likely to have profound impact on further tailoring therapies that are likely to improve outcomes, diminish toxicity and ultimately pave the pathway for a healthier population.

Mechanical thrombectomy by stent retriever for the treatment of arterial ischemic stroke in a pediatric patient with acute lymphoblastic leukemia: A case report

Introduction: Arterial ischemic stroke (AIS) caused by occlusion of large vessels in childhood is a devastating rare condition that can contribute to long-term disabilities. Childhood leukemia is identified as a recognized risk factor for ischemic strokes. Mechanical thrombectomy is standard of care for large vessel occlusions in adults. However, there are still no definite recommendations regarding application and outcomes of endovascular thrombectomy and the devices used for pediatric patients with arterial ischemic stroke. Case presentation: We report a 13-year-old female with acute lymphoblastic leukemia who developed AIS due to thrombosis in the left internal carotid and proximal middle cerebral artery in the induction phase of treatment. The patient underwent successful mechanical thrombectomy via Solumbra by using “Embolus Retriever with Interlinked Cages (ERIC)” stent retriever and Sofia plus catheter which resulted in successful recanalization of ICA and MCA. Discussion: Selected pediatric patients with AIS due to large vessel occlusions can benefit from mechanical thrombectomy. Although the recently published literature demonstrated the efficacy and safety of MT in children, strong guideline recommendations are still absent. At present, the last AHA/ASA guidelines for early management of AIS recommends intravenous thrombolysis and endovascular therapy in adults, whereas controversy still exists in children. An urgent approach within the defined therapeutic time frame and a multidisciplinary team specialized in pediatric stroke with professional trained interventional neuroradiologist is essential for achieving optimal results. Conclusion: Mechanical thrombectomy provides promising results with high rates of arterial recanalization and favorable outcomes in pediatric patients with AIS.

Clinical features and long-term prognostic analysis of relapsed pediatric acute lymphoblastic leukemia

Objective: To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse (HR=3.91, 95%CI 1.96-7.79; HR=4.15, 95%CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse (HR=6.50, 95%CI 2.58-16.34; HR=5.19, 95%CI 1.78-15.16), with ETV6::RUNX1 (HR=0.23, 95%CI 0.07-0.74) and HSCT after relapse (HR=0.24, 95%CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions: Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

Reducing Learning and Psychosocial Disparities in Latino Children with Cancer: A Randomized Intervention Trial.

We developed a high-intensity parenting intervention (HIP) to help parents support the academic success of childhood cancer survivors (CCSs), who often face post-treatment challenges affecting their school-related functioning. This randomized controlled trial (NCT03178617) evaluated HIP's efficacy compared to lower-intensity, single-session, treatment-as-usual services (LIP) in Latino families. Primary outcomes were parenting efficacy and CCSs' school functioning; secondary outcomes included parenting knowledge and measures of CCSs' academic performance, attention, and functioning outside of school. 106 Latino survivors of childhood leukemia and lymphoblastic lymphoma (aged 6-12 years) and their parents were randomly assigned to HIP (n = 54) or LIP (n = 52). Linear mixed-effects models evaluated group differences across baseline, 6-month (T2), and 12-month (T3) assessments. Parenting efficacy and knowledge improved significantly in the HIP arm, resulting in higher scores vs LIP at T2 and T3 (P ≤ .01). No significant between-group differences were found in child school functioning; however, HIP children showed significantly better social functioning and performance on one measure of attention (CPT-3 commissions) at T3 (P < .05). While HIP adherence challenges were observed, with only 33 (61%) completing the intervention, exploratory analyses suggest that benefits were most evident among those who fully engaged. Satisfaction and perceived benefit were greater for HIP vs LIP at both time points (P < .05). Our results suggest the potential value of parent-directed behavioral interventions like HIP for CCSs and their families. Further studies are needed to address participation barriers and enhance engagement to maximize and sustain benefits.

Quantification of deoxythioguanosine in human DNA with LC-MS/MS, a marker for thiopurine therapy optimisation.

In the treatment of diseases such as acute childhood leukaemia (ALL) and inflammatory bowel disease (IBD), the thiopurines azathioprine, 6-mercaptopurine, and 6-thioguanine are used. Thiopurines are antimetabolites and immunomodulators used to maintain remission in patients. They are all prodrugs and must be converted into thecompeting antimetabolites thioguanosine triphosphate and deoxythioguanosine triphosphate for final incorporation into RNA or DNA. The current therapeutic drug monitoring (TDM) method measures the sum of the formed metabolites in the sample, after acidic hydrolysis at high temperature. In this work, the goal is to measure these drugs closer to their pharmacological endpoints, once incorporated into DNA. After extracting DNA from whole blood, followed by DNA hydrolysis, 2'-deoxythioguanosine (dTG) and the complementary natural nucleobase 2'-deoxycytidine (dC) were measured. Chromatographic separation on a HSS T3 column followed by mass spectrometric detection was performed in multi-reaction monitoring (MRM) mode on a Xevo TQ-XS with ESI in positive mode, within 5 min. The concentration range for dTG was 0.04-5 nmol/L, and for dC, 0.1-12.5 µmol/L. The lower limit of detection was determined to a concentration of 0.003 nmol/L for dTG and 0.019 µmol/L for dC. The intra- and inter-assay imprecision for the quality controls ranged between 3.0 and 5.1% and between 8.4 and 10.9%, respectively. Sample stability for up to 4 years is shown. In summary, a sensitive method to quantify the thiopurines incorporated into DNA as dTG has been developed and will be used in further clinical studies for a better understanding of the mode of action of the thiopurines and the use of this method in TDM.

Infection Mortality in Acute Promyelocytic Leukemia in Children

Abstract Background Acute promyelocytic leukemia (APL) is a rare entity in children. The percentage of APL patients is 5-7% of all pediatric acute myeloid leukemia cases; a higher frequency (about 20%) is reported in children of Latino/Hispanic ancestry. The introduction of trans retinoic acid has been crucial for both antileukemic efficacy in APL and for prevention of early deaths. Furthermore, the use of arsenic trioxide (ATO) demonstrated to be highly effective in achieving high cure rates with reduced toxicity. However, there is a paucity of data concerning infection related deaths in APL. The objective was to describe the percentage of infection-related-deaths in APL in children; to describe the event free survival (EFS) and describe other main complications observed. Methods We identified 30 patients, as part of the Hospital Alejandro Posadas registry from a single center. We conducted a retrospective observational descriptive analysis. The patients were treated with the GIMEMA-AIDA 2000 protocol (n=23, 76.7%) and 1-LPA pediatrico-18-GALTA/CLEHOP (n=6, 20%). One patient died before treatment was given. The patients were diagnosed between 2000 to 2022. We used frequencies for descriptive variables, Chi2 /Fisher test for categorical data and time to event techniques for survival analysis. Any cause of mortality was extracted and analyzed. Results There were 66.7% of males; and median age was 12-year (IQR 8-15). PML-Rar alfa was positive (cytogenetics) in 23 (76.7%); Negative 6 (20%) and failed in 1 patient (3.3%). 100% had positive molecular biology for PML-rarAlfa transcript. Median white cells were 3.35x 109 /l (IQR 1.675-13.25). The patients were classified as high-risk (n=10, 33.3%) and standard risk (n=20, 66.7%). Four patients showed molecular relapse, 2 had CNS and one bone marrow involvement. Three patients died (10%), 2 due to endocranial hemorrhage, 1 as a consequence of complications of a hematological relapse. No patient died due to microbiologically documented infection or febrile neutropenia. With a mean estimated survival time (median not achieved) in years of 17.7 years, (CI 95% 14.6-20.7) the event free survival was 79% (SE 0.75), with 6 events. Cumulative competitive incidence of relapse 14% (SE 0.65). Conclusion In patients with APL, we could not find infections as cause of death. The overall results of APL management were very promising. Figure 1. Event Free Survival Acute Promyelocytic Leukemia.

The evolving hematopoietic niche during development.

Mammalian hematopoietic stem cells (HSCs) emerge from the hemogenic endothelium in the major embryonic arteries. HSCs undergo a complex journey first migrating to the fetal liver (FL) and from there to the fetal bone marrow (FBM), where they mostly remain during adult life. In this process, a pool of adult HSCs is produced, which sustains lifelong hematopoiesis. Multiple cellular components support HSC maturation and expansion and modulate their response to environmental and developmental cues. While the adult HSC niche has been extensively studied over the last two decades, the niches present in the major embryonic arteries, FL, FBM and perinatal bone marrow (BM) are poorly described. Recent investigations highlight important differences among FL, FBM and adult BM niches and emphasize the important role that inflammation, microbiota and hormonal factors play regulating HSCs and their niches. We provide a review on our current understanding of these important cellular microenvironments across ontogeny. We mainly focused on mice, as the most widely used research model, and, when possible, include relevant insights from other vertebrates including birds, zebrafish, and human. Developing a comprehensive picture on these processes is critical to understand the earliest origins of childhood leukemia and to achieve multiple goals in regenerative medicine, such as mimicking HSC development in vitro to produce HSCs for broad transplantation purposes in leukemia, following chemotherapy, bone marrow failure, and in HSC-based gene therapy.

Abstract A079: The impact of Indigenous American ancestry on the risk of acute lymphoblastic leukemia and the implications for future study designs

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino (H/L) children having up to 1.4 times the rate of ALL compared to their non-Hispanic White counterparts. This disparity has not been fully explained by environmental factors, suggesting the role of understudied genetic variants, particularly ones found in Indigenous American (IA) ancestry inherited by Latinos. In this study, we characterized the impact of IA ancestry on the frequency and effect size of known ALL risk alleles. We found that elevated risk of ALL in Latinos may be conferred by increased frequency of risk alleles due to IA ancestry. For instance, in an analysis of Latinos from the California Cancer Linkage Project (CCRLP; 1,930 cases, 2,103 controls) and the California Childhood Leukemia Study (CCLS; N = 605 cases, 515 controls), we found that, across independent known ALL loci (N=21), more loci than expected by chance showed a significant association between IA ancestry and increasing risk (p = 0.015). Compared to randomly-sampled, frequency-matched alleles from the genome, the risk alleles at all known ALL loci also showed a significant association with IA ancestry (46.9 % for known risk alleles vs. 43.5 % for matched alleles; ). The IA haplotype had 1.39 times the odds (95% CI: 1.35 – 1.43; ) of harboring the risk allele compared to the non-IA haplotype. Conversely, in a combined Latino sample of 2,535 cases and 9,035 controls, we found no evidence of GxAncestry interaction on ALL risk across all known loci (min P = 0.0026, prior to adjusting for multiple testing), suggesting that ALL risk alleles do not have increased effects on the IA ancestry background. This lack of synergism between local ancestry and genotype in ALL has methodological implications for gene discovery in admixed populations. To explore this, we implemented Tractor, a method that models genotype effects by ancestry, and thus is best powered in the presence of effect size heterogeneity by ancestry. Across known loci, we found that Tractor had 36.1% decreased power compared to standard GWAS. Taken together, our results suggest that the disproportionate burden of ALL in Latino populations may arise from the enrichment of risk alleles within the IA ancestry component, possibly driven by immunity- related selective pressures. Finally, future genetic studies of ALL in Latino patients may benefit from methods that incorporate contributions from ancestry to increase the statistical power in identifying associations, rather than leverage effect size heterogeneity across ancestries. Citation Format: Jalen Langie, Libby Morimoto, Xiaomei Ma, Catherine Metayer, Joseph L. Wiemels, Adam J. de Smith, Charleston W.K. Chiang. The impact of Indigenous American ancestry on the risk of acute lymphoblastic leukemia and the implications for future study designs [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A079.

Domestic radon exposure and childhood cancer risk by site and sex in 727 counties in the United States, 2001–2018

BackgroundChildhood cancer has few established risk factors and environmental influences are underexplored. This ecologic study investigated the association between domestic radon exposure and childhood cancer risk in a large sample of United States (U.S.) counties. MethodsMonthly ZIP code-level basement radon estimates from a geographic machine learning model were aggregated annually to counties, analyzed as continuous and dichotomized (cut point: 74 Bq/cubic meter (Bq/m3) or 2.0 picocuries/L (pCi/L)) versions, and lagged by one year. Annual county-level counts of sex- and site-specific (all, leukemia, brain and central nervous system [CNS], and other sites) incident cancer diagnoses among those 0–19 years from 2001 to 2018 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database. Sex- and site-specific counts were modeled as zero-inflated Poisson distributions in a Bayesian spatiotemporal framework and sequentially adjusted for random and fixed confounder effects. ResultsIn 727 counties across 14 states, the average population aged 0–19 years was 41,599 people at baseline. Results from fully adjusted spatiotemporal statistical models indicated 1.05 (95% credible interval, CrI: 1.00, 1.09) times higher relative risks (RRs) of leukemia among both sexes and a RR of 1.06 (95%CrI: 1.00, 1.12) in males from a 50 Bq/m3 (1.35 pCi/L) increase in radon concentration the year prior. For radon exposures ≥74 Bq/m3 (2.00 pCi/L) the year prior, RRs were 1.08 (95%CrI: 1.02, 1.15) for both sexes and 1.12 (95%CrI: 1.04, 1.22) for females. No associations were found with other cancer sites or sexes from prior year radon exposures. ConclusionsCounty-level childhood leukemia risk in both sexes were associated with average radon levels below U.S. Environmental Protection Agency guidelines recommending mitigation (148 Bq/m3 or 4.00 pCi/L). These findings warrant further investigation using population-based and individual-level study designs.

Adipocyte maturation impacts daunorubicin disposition and metabolism.

Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event-free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated. This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR). Using targeted LC-MS/MS multi-analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR-metabolizing enzymes aldo-keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR-metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR-, CBR-specific inhibitors. This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4- to 60- folds, p < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites. Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR-metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.

AML-259 Survival and Toxicity of Acute Promyelocytic Leukemia in Children: Single-Center Experience in Tashkent

AML-259 Survival and Toxicity of Acute Promyelocytic Leukemia in Children: Single-Center Experience in Tashkent

Analyzing leukemia content on social media: a comprehensive cross-sectional examination of Instagram and YouTube

Introduction: Leukemia is a hematologic malignancy characterized by the uncontrolled proliferation of abnormal white blood cells. Patients with childhood leukemia may turn to social media for emotional support and information. This study aimed to identify the quality, reliability, understandability, and actionability of posts related to leukemia on YouTube and Instagram. Methods: Apify, a web scraping tool was used to gather relevant posts. The top 100 posts in each hashtag “leukemia,” “childhoodcancer,” “childhoodcancerawareness,” “leukemiaawareness” on Instagram, and the top 60 videos on YouTube for the term “leukemia” were scraped on 24 September 2023, resulting in the collection of 361 Instagram and 58 YouTube videos. All posts and videos in English and related to leukemia were included in the analysis, and thus, a total of 231 Instagram posts and 56 YouTube videos were evaluated, guided by the strengthening the reporting of cohort studies in surgery guidelines and utilized standardized tools [Global Quality Scale (GQS), modified DISCERN, and Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V)]. Data analysis was done in R Studio (4.3.1.); Kruskal–Wallis test was used to determine statistical significance. Results: YouTube videos demonstrated commendable standards with moderate quality and reliability (GQS 3.1, modified DISCERN 2.9, PEMAT-A/V understandability averaged 89%, and actionability averaged 50%). The impact of the uploader type on content quality and reliability was insignificant on both platforms. However, a notable correlation between YouTube video duration and quality scores underscored the potential influence of content length on information presentation. Instagram posts exhibited comparatively lower scores (GQS 2, modified DISCERN 1.8, PEMAT-A/V understandability averaged 56%, and actionability averaged 15%), indicating a need for enhanced content quality. Personal narratives emphasized the significant role of lived experiences in shaping content. Conclusion: Despite high understandability, actionable content, particularly on Instagram, necessitated improvement, revealing a potential gap in disseminating practical information. While personal narratives contributed significantly, lower reliability scores highlighted inherent challenges, underscoring the pivotal role of healthcare provider engagement and content validation.

Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

Central nervous system complications during treatment in childhood acute leukemia.

Central nervous system (CNS) complications can be seen in patients with leukemia, depending on the disease itself and the chemotherapeutic agents used. This study focused on CNS complications during treatment in children with acute leukemia in a single pediatric institution. CNS complications were evaluated retrospectively in 115 patients with ALL and AML. Patients with CNS leukemia infiltration at the time of diagnosis or during a neurological event, late-onset encephalopathy, peripheral neuropathy, or a previous history of neurological abnormalities were excluded from the study. A total of 115 children's clinical records with acute leukemia over a four-year period were reviewed. Acute CNS complications developed in 23.1% of acute myeloid leukemia (AML) patients and in 13.5% of acute lymphoblastic leukemia (ALL) patients. CNS complications developed most frequently during the induction phase of the treatment (66.7%). Seizures were the most common symptom (9 patients, 50%), followed by hemiparesis (4 patients, 22.2%) and headache (4 patients, 22.2%). Six patients (33.3%) had chemotherapy-induced toxic leukoencephalopathy, two (11.1%) had Wernicke's encephalopathy, and one patient (5.6%) each had sinus vein thrombosis, posterior reversible encephalopathy syndrome, and CNS infection. Sequelae occurred in three patients (16.7%), and only one patient (5.6%) died due to a CNS complication. Awide variety of symptoms can be observed in childhood leukemia, depending on the disease itself, the chemotherapeutic agents used and a lot of other conditions such as nutritional problems. Our research shows that several CNS complications might manifest with similar symptoms; differentiated diagnosis between the underlying etiological reasons can be made by neuroimaging.

Changes in the Metabolome of Serum and Cerebrospinal Fluid During Intensive Treatment of Acute Lymphoblastic Leukemia in Children

Changes in the Metabolome of Serum and Cerebrospinal Fluid During Intensive Treatment of Acute Lymphoblastic Leukemia in Children