Pediatric Blood & Cancer[JOURNAL]
Sun
200 papers
Emerging roles of ADAM6 and PRSS1 as novel diagnostic/prognostic biomarkers for acute lymphoblastic and myeloid leukemia in adults.
Anis HM, Rakha NM, Kassem DH … +1 more , Kamal AM
BMC Cancer · 2025 May · PMID 40382561 · Full text
BACKGROUND: Acute leukemia is an aggressive, highly heterogeneous hematological malignancy. A Disintegrin And Metalloproteinase Domain-6 (ADAM6), a member of ADAMs family, has emerged recently as a potential novel player...
BACKGROUND: Acute leukemia is an aggressive, highly heterogeneous hematological malignancy. A Disintegrin And Metalloproteinase Domain-6 (ADAM6), a member of ADAMs family, has emerged recently as a potential novel player in pediatric acute lymphoblastic leukemia (ALL), and its function remains largely elusive. Serine Protease-1 (PRSS1) is another emerging molecular mediator in cancer development. However, its role in acute leukemia has not been adequately studied. Interestingly, ADAM6 and PRSS1 were identified among the genes with the highest percentage of chromosomal changes in profiled B-cell precursor ALL patients. Both are emerging novel mediators of extracellular matrix (ECM) remodeling. Thus, this study was designed to investigate the roles of ADAM6 and PRSS1 in ALL and acute myeloid leukemia (AML) in adults. METHODS: Adult patients with de novo ALL (n = 36), de novo AML (n = 40), and healthy control subjects (n = 55) were enrolled in this study. Circulating serum levels of ADAM6 and PRSS1 were measured by ELISA technique. RESULTS: Serum levels of ADAM6 were significantly higher in ALL and AML patients compared to healthy control subjects (208.7(178.3-337.3), 186.4(155.3-479.6), and 78.6(55.8-101.8) pg/ml, p < 0.0001), respectively. Whereas, serum levels of PRSS1 were found to be significantly lower in ALL and AML patients compared to healthy controls (175.1(153.7-232.2), 177.9(145.3-206.4), and 247.5(204.3-375.3) ng/ml, p < 0.0001), respectively. Both ADAM6 and PRSS1 exhibited a very good diagnostic potential by ROC analyses. ADAM6 levels significantly varied between CD22/CD22 and CD45/CD45, while PRSS1 levels significantly varied between HLA-DR/HLA-DR ALL patients, suggesting their prognostic implications. Also, ADAM6 and PRSS1 were found to be significantly correlated with each other. CONCLUSION: The results of the current study portray ADAM6 and PRSS1 as new potential diagnostic/prognostic biomarkers and potential therapeutic targets in adult acute leukemia patients, and shed light on their role as novel interrelated mediators possibly implicated in tumor micro-environment remodeling.
Study protocol of an early randomized intervention trial assessing the metabolic effects of two levels of exercise intensity in children undergoing cancer treatment: the APACIS study.
Thomas J, Filleron T, Auriol F … +2 more , Laurens C, Pasquet M
BMC Cancer · 2025 May · PMID 40346598 · Full text
BACKGROUND: Insulin sensitivity is a key factor of the development of metabolic diseases, highly prevalent in adult survivors of childhood cancers. The aim of the Adapted Physical Activity for children treated for Cancer...
BACKGROUND: Insulin sensitivity is a key factor of the development of metabolic diseases, highly prevalent in adult survivors of childhood cancers. The aim of the Adapted Physical Activity for children treated for Cancer and Insulin-Sensitivity (APACIS) study is to investigate the effects of two exercise programs started as early as diagnosis on metabolic profile and physical health. METHODS: APACIS is a trial that includes children at diagnosis of all pediatric cancers which are randomly allocated to the Soft group - for low intensity physical activity - or to the Strong group - for mixed, high intensity exercise. Both programs are done at least twice weekly for 30 to 60 min over 6 months, adapted to the health status of the children, with a follow-up of 18 months. The primary objective is the change in insulin sensitivity measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at 0, 3, 6, 12 and 24 months between the two groups. The secondary objectives include changes in cholesterol, triglycerides and cortisol blood levels, state of undernourishment, cardiorespiratory fitness (based on peak rate of oxygen uptake of the 6 Minute Walk Test), flexibility (sit and reach flexibility test), fat mass distribution (Waist-to-Hip Ratio) and level of physical activity assessed by questionnaire at 0, 3, 6, 12 and 24 months. On-therapy metabolic adaptation in the different patient groups will also be evaluated by an integrated pipeline combining the detection of 150 metabolites, with metabolic pathway enrichment and network mapping. This approach will be complemented by an analysis of intestinal and oral microbiota, to identify the species impacted by treatments and the influence of exercise on these toxicities. DISCUSSION: The APACIS study investigates the metabolic, motor, and nutritional effects in children with cancers performing low versus high intensity exercise with an innovative approach consisting of early practice since diagnosis. It will contribute to better personalize physical activity prescription during treatment of pediatric cancers. TRIAL REGISTRATION: The study has been registered on ClinicalTrials.gov (NCT05383092) the 7 of November, 2022.
The evolving therapeutic revolution in adult acute lymphoblastic leukemia.
Kantarjian H, Jain N, Litzow MR … +6 more , Luger SM, Papayannidis C, Ribera JM, Short NJ, Chifotides HT, Jabbour E
Cancer · 2025 May · PMID 40323723 · Full text
The past decade has witnessed remarkable advances in deciphering the pathophysiology of acute lymphoblastic leukemia (ALL) and in developing novel targeted therapies. Basic research and genomic mapping have identified ne...
The past decade has witnessed remarkable advances in deciphering the pathophysiology of acute lymphoblastic leukemia (ALL) and in developing novel targeted therapies. Basic research and genomic mapping have identified new prognostic biomarkers, targets, and ALL subtypes (e.g., Philadelphia-like ALL). The ongoing therapeutic revolution in ALL is driven by the addition to the treatment arsenal of therapies that target the ABL fusions, like the BCR::ABL1 tyrosine kinase inhibitors, as well as novel agents that target CD19 and CD22: the CD22 antibody-drug conjugate inotuzumab ozogamicin, the bispecific CD3/CD19 T-cell engager antibody blinatumomab, and CD19 chimeric antigen receptor T-cell therapies. These combinations have improved the long-term survival rates in B-cell ALL to 70%, and in Philadelphia chromosome-positive ALL to 80%-90%. The desired goals are to achieve cure rates comparable to those in pediatric ALL and to reduce or eliminate the need for prolonged intensive/maintenance chemotherapy and associated toxicities.
Efficacy of photobiomodulation for the prevention and treatment of chemotherapy-induced oral mucositis in pediatric patients with hematologic cancers: a randomized clinical trial.
Lavaee F, Rezazadeh F, Amanati A … +4 more , Sookhakian A, Amiri MA, Dehghani N, Fereidouni K
BMC Cancer · 2025 May · PMID 40316940 · Full text
BACKGROUND: Oral mucositis (OM) is a debilitating treatment-related complication that affects most children undergoing chemotherapy. This dual-arm clinical trial aimed to evaluate the efficacy of photobiomodulation (PBM)...
BACKGROUND: Oral mucositis (OM) is a debilitating treatment-related complication that affects most children undergoing chemotherapy. This dual-arm clinical trial aimed to evaluate the efficacy of photobiomodulation (PBM) for prevention and photodynamic therapy (PDT) using indocyanine green (ICG) and low-level laser for treating methotrexate (MTX)-induced OM in pediatric patients with hematologic cancers. METHODS: In the prevention arm, patients were initially assigned to a control group (received no laser) and subsequently reassigned to a PBM group in their next cycle, allowing intra-patient comparison under similar chemotherapy protocols. In the treatment arm, patients diagnosed with OM were randomly assigned to either a control group (sham laser) or a PDT group. RESULTS: In the prevention arm, PBM led to a significant reduction in the incidence of OM from 66.67% to 6.67% (p < 0.05). In the treatment arm, the PDT group showed a significant reduction in the scores of all scales (WHO, NCI, and WCCNR) at both 3 days and 5 days after starting the treatment compared to the control group (p < 0.05). Moreover, the reduction in the NCI score from the third to the fifth days after the starting treatment is higher in the PDT group compared to the control group (p < 0.05). CONCLUSION: PBM appears to be a safe and effective approach for the prevention of MTX-induced OM in pediatric patients with hematologic cancers. Additionally, PDT using ICG and a low-level laser demonstrates promising results in treating OM lesions. Therefore, these findings highlight the efficacy of PBM for managing MTX-induced OM in this patient group. TRIAL REGISTRATION: The study has been registered on irct.behdasht.gov.ir on 4 December 2022 (Trial Registration Number: IRCT20120101008585N16).
Impact of neighborhood archetypes on overall mortality among young patients with acute leukemia in California.
Winestone LE, Yang J, Banerjee T … +7 more , Sangaramoorthy M, Kahn J, Abrahão R, Keegan TH, Cheng I, Gomez SL, Shariff-Marco S
Cancer · 2025 May · PMID 40304597 · Full text
INTRODUCTION: Residence in lower socioeconomic neighborhoods is associated with lower survival in children, adolescents, and young adults with leukemia. We sought to evaluate the impact of neighborhood archetypes on acut...
INTRODUCTION: Residence in lower socioeconomic neighborhoods is associated with lower survival in children, adolescents, and young adults with leukemia. We sought to evaluate the impact of neighborhood archetypes on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) survival. METHODS: Patients aged 0 to 39 years diagnosed with ALL or AML from 2006 through 2016 in the California Cancer Registry were included. Nine-class neighborhood archetypes, generated by latent class analysis of 39 social and built environment attributes at the census tract level, were the primary exposure of interest. Cox proportional hazards models were used for statistical analyses, stratified by age. RESULTS: Among 8776 patients, 72% had ALL and 28% had AML. For ALL, increased risk of mortality was observed in mixed socioeconomic status suburbs (adjusted hazard ratio, 1.39; 95% CI, 1.06-1.84) and Hispanic small towns (adjusted hazard ratio, 1.33; 95% CI, 1.03-1.84) relative to upper middle-class suburbs. For AML, neighborhood archetypes were not associated with mortality. When stratified by age, we observed associations between neighborhood archetypes (mixed socioeconomic status class suburb, inner city, Hispanic small towns) and mortality in pediatric but not young adult ALL patients. CONCLUSIONS: Our findings demonstrate that neighborhood archetypes efficiently account for complex interactions across social and built environment attributes with leukemia survival. The greater effects of neighborhood archetype in pediatric ALL survival, as compared to AML, may be related to the prolonged, outpatient nature of ALL maintenance therapy and the challenges associated with treatment adherence among patients residing in disadvantaged neighborhoods.
A framework-based guide for adapting and implementing primary care-based pediatric interventions to the pediatric oncology setting: HPV PROTECT as an exemplar.
Klosky JL, Cherven B, Gilkey MB … +13 more , Aye J, Castellino SM, Gramatges MM, Lindemulder S, Russell TB, Turcotte LM, Campos González PD, Skipper KE, Chollette V, Mitchell SA, Colditz GA, Bhatia S, Landier W
Cancer · 2025 May · PMID 40297935 · Full text
Pediatric oncology providers can help childhood cancer survivors protect their health by ensuring they receive routine preventive services. Management of these services by survivorship providers is necessary due to patie...
Pediatric oncology providers can help childhood cancer survivors protect their health by ensuring they receive routine preventive services. Management of these services by survivorship providers is necessary due to patients' suboptimal rates of re-engaging with pediatric primary care after treatment completion. This is especially the case with cancer prevention interventions, like human papillomavirus (HPV) vaccination, as survivors have greater confidence in the recommendations offered by their oncology versus primary care providers when counseling of this nature occurs. As these preventive pediatric interventions have traditionally been tested and delivered in primary care, they may lack appropriate tailoring or adaptation to the pediatric oncology setting. This article serves as a guide for using a best practice (ADAPT) framework for adapting and implementing a provider-focused intervention to increase the uptake of HPV vaccination in the pediatric oncology setting. Once the rationale and guiding principles for engaging in this process are presented, the intervention adaptation processes are illustrated via descriptions of assessment, planning, piloting, evaluation, implementation, and maintenance. Additional considerations specific to the pediatric oncology setting are also provided. By applying ADAPT or other appropriate frameworks when adapting and implementing pediatric interventions in the cancer survivorship setting, progress will be made toward establishing a gold standard in approaching these tasks. Ultimately, these collective efforts will maximize the likelihood of effective intervention delivery and reduce health risk in this vulnerable population.
Testicular and ovarian Juvenile granulosa cell tumors in children and adolescents: Analysis of 113 patients registered to the German Registry for Rare Pediatric Tumors (STEP).
Schneider DT, Witowski A, Abele M … +10 more , Benesch M, Bernbeck B, Blessing T, Brummel B, Calaminus G, Göbel U, Graf N, Vokuhl C, Schultz KAP, Brecht IB
Cancer · 2025 May · PMID 40272823 · Full text
BACKGROUND: In juvenile granulosa cell tumors (juvGCTs), impaired survival was reported after preoperative tumor rupture, peritoneal metastases, or high mitotic rate (≥20 mitoses per 10 high-power fields). Therefore, a r...
BACKGROUND: In juvenile granulosa cell tumors (juvGCTs), impaired survival was reported after preoperative tumor rupture, peritoneal metastases, or high mitotic rate (≥20 mitoses per 10 high-power fields). Therefore, a risk stratification was developed to select patients for chemotherapy. METHODS: Between 2001 and 2019, 89 female patients and 24 male patients were prospectively enrolled. Histopathologic classification was according to the World Health Organization classification, and staging was according to Children's Oncology Group and International Federation of Gynecology and Obstetrics classification. RESULTS: Testicular juvGCTs were detected as scrotal swelling during infancy. No recurrences were reported after orchiectomy. Patients with ovarian juvGCTs presented at a median age of 9.8 years with abdominal discomfort, isosexual precocity, or amenorrhea. After tumor resection, two of 52 patients with stage IA disease, one of 14 with stage IC1 disease (intraoperative rupture), 13 of 18 with stage IC2 or IC3 disease (preoperative rupture), and all five patients with stage II/III disease received chemotherapy. Four recurrences with two deaths were reported. Three recurrent tumors were initially stage IA with a high mitotic rate, and one was a stage II tumor. No recurrences were observed among patients who had stage IC2/IC3 disease, who had unfavorable prognoses in historical cohorts. The 5-year event-free survival was 0.95 ± 0.03 (85 of 89 patients), and overall survival was 0.97 ± 0.02 (87 of 89 patients). CONCLUSIONS: Testicular and ovarian juvGCTs are clinically distinct entities. Although testicular juvGCTs exclusively present during infancy and have an excellent prognosis, ovarian juvGCTs may arise at any age and constitute potentially aggressive tumors. Centralized reference diagnostics and the establishment of counseling structures for the treatment of patients with ovarian juvGCTs improved prognosis compared with historical groups. The mitotic rate and incomplete surgery were identified as important risk factors in addition to tumor stage and should be considered in the risk-stratification of therapy.
Ovarian juvenile granulosa cell tumor: A report from the International Ovarian and Testicular Stromal Tumor and International Pleuropulmonary Blastoma/DICER1 Registries.
Harris AK, Nelson AT, Watson D … +20 more , Mallinger PHR, Messinger YH, Frazier AL, Stering A, Snyder SL, Levy CF, Kamihara J, Herzog CE, Lagmay J, Foresto S, Chen KS, Devins KM, Young RH, Hill DA, Dehner LP, Tadavarthy AK, Stall JN, Billmire DF, Schneider DT, Schultz KAP
Cancer · 2025 May · PMID 40267023 · Full text
BACKGROUND: Ovarian juvenile granulosa cell tumors (juvGCT) are rare sex cord-stromal tumors that occur primarily in children and adolescents. This study summarizes the clinical presentation and outcomes of patients with...
BACKGROUND: Ovarian juvenile granulosa cell tumors (juvGCT) are rare sex cord-stromal tumors that occur primarily in children and adolescents. This study summarizes the clinical presentation and outcomes of patients with juvGCT. METHODS: Patients were enrolled in the International Ovarian and Testicular Stromal Tumor and/or International Pleuropulmonary Blastoma/DICER1 Registries. Available medical records were abstracted, and pathology was centrally reviewed. Surgical staging was classified using the 2014 International Federation of Gynecology and Obstetrics (FIGO) criteria. RESULTS: In total, 70 patients with juvGCT enrolled and were diagnosed between 2001 and 2024; most patients (81%, 57 of 70) presented with FIGO stage I disease. Adjuvant chemotherapy was given in 30% (21 of 70); all regimens were platinum-based. Three-year event-free survival among patients with stage IA tumors was 80.2% (95% confidence interval [CI], 62.4%-100.0%), IC1 was 87.4 (95% CI, 72.4%-100.0%), IC2-IC3 was 63.6% (95% CI, 40.7%-99.5%), and II-IV was 48% (95% CI, 24.6%-93.8%). Of the patients with recurrent juvGCT with known mitotic index (MI), all had MI greater than 19 mitoses per 10 high power fields (HPF) at diagnosis. CONCLUSION: Outcomes were worse for patients with FIGO stage ≥IC2 disease and for tumors with >19 mitoses per 10 HPF. Given the prognostic significance of MI, the authors strongly recommend the assessment of MI for all juvGCTs. More information about tumor biology is critical to identify which patients may benefit from adjuvant chemotherapy and to facilitate the development of novel therapies.
Consensus recommendations regarding local and metastasis-directed therapies in the management of relapsed/recurrent Ewing sarcoma.
Shah C, Campbell SR, Murphy E … +11 more , Braunstein S, Dietz MS, Binitie O, Kastenberg ZJ, Yanagawa J, Halpern J, Kis B, Hunt S, Yazdanpanah F, Gupta A, Trucco M
Cancer · 2025 May · PMID 40251761 · Full text
Limited randomized or prospective data are available to guide local/metastasis directed therapy (LMDT) in relapsed/recurrent Ewing sarcoma (RR-ES), resulting in uncertainty regarding best clinical practice for these pati...
Limited randomized or prospective data are available to guide local/metastasis directed therapy (LMDT) in relapsed/recurrent Ewing sarcoma (RR-ES), resulting in uncertainty regarding best clinical practice for these patients. This report reviews the available literature on LMDT approaches and provides consensus recommendations regarding therapeutic decision making, timing, and indications for the use of LMDT in the management of RR-ES. LMDT should be considered on a case-by-case basis to assess appropriateness, optimal timing/modality, palliative versus curative intent, and its role in relation to chemotherapy. One commonly used LMDT is radiotherapy (RT), which can be delivered through standard, hypofractionated, or stereotactic techniques based on factors including prior RT, tumor size, and/or location. Chemotherapy can be combined with RT, although prospective data are limited in the relapse setting. Surgery for LMDT not only addresses the tumor but also provides tissue for analysis, though the potential surgical morbidity based on location, extent of resection, and recovery complications should be considered. Interventional radiology approaches also can procure tumor tissue while delivering LMDT; there are several different procedures available based on the location, size, and extent of disease. Finally, a combination of LMDT approaches can be used for patients with RR-ES. Decisions regarding the management of RR-ES should involve a multidisciplinary team and factor in the burden of disease, progression-free interval, life expectancy, toxicity profiles of LMDT, and quality of life. In such patients, informed and shared decision making with patients and their families is paramount.
Advancing the implementation of quality-assured oncological exercise therapy in Germany: protocol for the IMPLEMENT project.
Brandes M, Berling-Ernst A, Baurecht H … +30 more , Jensen W, Götte M, Herrmann A, Fuhr D, Schmidt H, Lucas A, Madl B, Elmers S, Schmidt T, Welker C, Golla A, Wehner A, Morlok D, Rueter J, Meuer J, Reitz M, Kersten J, Zimmer R, Gadczikowske Y, Stark R, Hegenberg K, Laxy M, Halle M, Jahn P, Bokemeyer C, Theurich S, Zeeb H, Leitzmann M, Baumann FT, IMPLEMENT consortium
BMC Cancer · 2025 Apr · PMID 40241071 · Full text
BACKGROUND: Although quality-assured oncological exercise therapy (qOET) has proven effective for cancer patients at any stage of treatment and during aftercare, it is not yet incorporated into standard care in Germany a...
BACKGROUND: Although quality-assured oncological exercise therapy (qOET) has proven effective for cancer patients at any stage of treatment and during aftercare, it is not yet incorporated into standard care in Germany and, to the best of our knowledge, in any other country. A collaboration involving eight German research institutions was initiated to investigate the barriers and facilitators to implementation and promote the wider dissemination of qOET for cancer patients across various settings in Germany. METHODS: The IMPLEMENT project is designed as an exploratory study with a quasi-experimental design and a mixed-methods approach, combining qualitative and quantitative data collection. Institutions involved in the treatment and/or aftercare of cancer patients will be approached to identify key barriers and facilitators of qOET. Based on these findings, a set of implementation strategies (IPS) will be developed, implemented, and evaluated to facilitate the delivery of qOET for cancer patients. We aim to develop a variety of IPS for different contexts: urban settings (e.g. qualifying local aftercare institutions to provide qOET); rural settings (e.g. a hybrid approach for areas with limited access to local qOET services); adult cancer patients (e.g. focussing on patient education); and children and young cancer patients (e.g. offering consultations with training therapy experts). Additionally, interface management, training concepts, digital support, and economic evaluation will be considered to further promote the wider dissemination of qOET. The impact of the IPS will primarily be measured by the reach of qOET, assessed by comparing the number of cancer patients receiving qOET before and after implementation. DISCUSSION: The aim of IMPLEMENT is to address key barriers and facilitators for the implementation of qOET in Germany, and to increase the number of cancer patients receiving qOET in the long term. Following the project, successful IPS will be disseminated for broader application. The IMPLEMENT consortium aims to make a significant contribution to the long-term integration of qOET into the standard care of cancer patients in Germany and prospectively for other countries as well. TRIAL REGISTRATION: Clin. TRIALS: NCT06496711. German Clinical Trial Register (Deutsches Register Klinischer Studien - DRKS): 00032292. Bavarian Cancer Research Center (Bayerisches Krebsforschungszentrum (BZKF bzw. ZKS): DZ-2024-2165-9.
Screening colorectal cancer associated autoantigens through multi-omics analysis and diagnostic performance evaluation of corresponding autoantibodies.
Qiu Z, Cheng Y, Liu H … +13 more , Li T, Jiang Y, Lu Y, Jiang D, Zhang X, Wang X, Kang Z, Peng L, Wang K, Dai L, Ye H, Wang P, Shi J
BMC Cancer · 2025 Apr · PMID 40240912 · Full text
BACKGROUND: This study aims to screen, validate novel biomarkers and develop a user-friendly online tool for the detection of colorectal cancer (CRC). METHODS: Multi-omics approach, comprising proteomic analysis and sing...
BACKGROUND: This study aims to screen, validate novel biomarkers and develop a user-friendly online tool for the detection of colorectal cancer (CRC). METHODS: Multi-omics approach, comprising proteomic analysis and single-cell transcriptomic analysis, was utilized to discover candidate tumor-associated antigens (TAAs). The presence of tumor-associated autoantibodies (TAAbs) in serum was subsequently assessed using enzyme-linked immunosorbent assays (ELISA) in 300 CRC patients and 300 healthy controls. Ten machine learning algorithms were utilized to develop diagnostic models, with the optimal one selected and integrated into an R Shiny-based GUI to enhance usability and accessibility. RESULTS: We identified twelve potential TAAs: HMGA1, NPM1, EIF1AX, CKS1B, HSP90AB1, ACTG1, S100A11, maspin, ANXA3, eEF2, P4HB, and HKDC1. ELISA results showed that five TAAbs including anti-CKS1B, anti-S100A11, anti-maspin, anti-ANXA3, and anti-eEF2 were potential diagnostic biomarkers during the diagnostic evaluation phase (all P < 0.05). The Random Forest model yielded an AUC of 0.82 (95% CI: 0.78-0.88) on the training set and 0.75 (95% CI: 0.68-0.82) on the test set, demonstrating the robustness of the results. Web-based implementations of CRC diagnostic tools are publicly accessible via weblink https://qzan.shinyapps.io/CRCPred/ . CONCLUSIONS: A five biomarker panel can server as complementary biomarker to CEA and CA19-9 in CRC detection.
The impact of a single HIIT intervention on the mobilization of NK cells and ILCs in adolescents and young adults (AYA) undergoing cancer treatment: an interventional controlled trial.
Deppe I, Beller R, Kiehl F … +5 more , Lazzari N, Bennstein SB, Reinhardt D, Dirksen U, Götte M
BMC Cancer · 2025 Apr · PMID 40229731 · Full text
OBJECTIVE: The study investigated the response of immune cells, particularly natural killer (NK) cells and innate lymphoid cells (ILCs), to acute exercise in adolescents and young adults (AYAs) undergoing cancer treatmen...
OBJECTIVE: The study investigated the response of immune cells, particularly natural killer (NK) cells and innate lymphoid cells (ILCs), to acute exercise in adolescents and young adults (AYAs) undergoing cancer treatment, to lower their treatment burden and evaluate the value of exercise in this vulnerable cohort. METHODS: An AYA cancer patient group (PG) (n = 20, 25 ± 7 years old) and an age-matched healthy control group (HG) (n = 20, 27 ± 5 years old) completed a twenty-minute high intensity interval training (HIIT) on a bicycle ergometer. Blood was taken at three timepoints during the intervention. Once immediately before (T0), once immediately after the intervention (T1), and after one-hour of recovery (T2). NK cells, ILCs, respectively their subpopulations, were determined by flow cytometry. RESULTS: Total NK cells (PG: p = 0.023; HG: p = 0.004), CD56NK cells (PG: p = 0.035; HG: p = 0.004), total ILCs (PG: p < 0.001; HG: p < 0.001), ILC1-like (PG: p = 0.001; HG: p = 0.004), ILC2 (PG: p = 0.006; HG: p = 0.003) and innate lymphoid cell precursors (ILCPs) (PG: p = 0.009; HG: p = 0.002) increased significantly from T0 to T1. CD56NK cells (HG: p = 0.011) increased significantly only in the HG. From T1 to T2 total NK cells (PG: p < 0.001; HG: p < 0.001), CD56NK cells (PG: p < 0.001; HG: p < 0.001), CD56NK cells (PG: p < 0.001; HG: p < 0.001), ILC2 (PG: p = 0.035; HG: p = 0.007) and ILCPs (PG: p = 0.006; HG: p = 0.003) decreased significantly. ILC1-like maintained their elevated cell count plateau during the recovery phase. No significant differences were found for NKp44ILC3 and for inter-group comparisons regarding the percentage changes of cell counts from T0 to T1 or T1 to T2. Younger age and higher heart rates (in percentage of age-predicted maximal heart rate) during the intervention were associated with an increased mobilization of immune cells, especially in NK cells and their subpopulations. CONCLUSION: We were able to show, that HIIT enhances the mobilization of NK cells and ILCs to the same extend in AYA cancer patients than in healthy controls. Our pilot study revealed, that exercise is likely to play an important role in the defense against pathogens and neoplastic cells and that AYA cancer patients might benefits from regular exercise programs during anti-cancer treatment. TRIAL REGISTRATION: The study was registered on 13.11.2022, registration number NCT05656651, in the international register of clinical trials https://www. CLINICALTRIALS: gov/ .
Multilevel mortality risk factors among pediatric hematology-oncology patients with deterioration.
Agulnik A, Robles-Murguia M, Chen Y … +45 more , Muñiz-Talavera H, Pham L, Carrillo A, Cardenas-Aguirre A, Costa J, Mendez Aceituno A, Acuña Aguirre C, Aguilar Roman AB, Alvarez Arellano SY, Andrade Sarmiento LA, Arce Cabrera D, Blasco Arriaga EE, De León Gutiérrez CM, Diaz-Coronado R, Diniz Borborema MDC, do Nascimento Othero Campacci M, Drumond Alberto L, Gonzalez NS, Herrera Almanza M, Jimenez Antolinez V, Laffont Ortiz MD, Lemos De Mendonça E Fontes L, López Facundo NA, López Vázquez CB, Lozano Lozano IM, Mijares Tobias JM, Mora Robles LN, Noriega Acuña B, Endo Marques FP, Pérez Fermín CK, Quijano Lievano ML, Ribeiro Pereira Aguiar De Paula A, Rios L, Rivera J, Sahonero MA, Salas Mendoza B, Sánchez-Martín M, Sepúlveda Ramírez J, Soto Chávez V, Velásquez Cabrera DM, Villanueva Hoyos EE, Zuñiga Quijano LY, Devidas M, Rodriguez-Galindo C, Escala de Valoracion de Alerta Temprana Study Group
Cancer · 2025 Apr · PMID 40193253 · Full text
BACKGROUND: Hospitalized pediatric hematology-oncology patients have frequent clinical deterioration events (CDEs) requiring intensive care unit (ICU) interventions and resulting in high mortality, particularly in resour...
BACKGROUND: Hospitalized pediatric hematology-oncology patients have frequent clinical deterioration events (CDEs) requiring intensive care unit (ICU) interventions and resulting in high mortality, particularly in resource-limited settings. This study identifies independent risk factors for CDE mortality in hospitals providing childhood cancer care in Latin America and Spain. METHODS: Centers implemented a prospective CDE registry, defined as unplanned transfer to a higher level of care, use of ICU-level interventions on the ward, or nonpalliative ward death. The authors analyzed registry data from April 2017 to December 2022. The primary outcome was CDEs mortality, defined as death occurring during ICU admission, <24 hours of ICU discharge, or end of ward-based ICU interventions. Multilevel modeling identified event-, patient-, and hospital-level independent risk factors for CDE mortality. RESULTS: Among 69 participating hospitals in 18 countries, 4134 CDEs were reported in 3319 pediatric hematology-oncology patients with an event mortality of 26.8% (1108 events). Of all CDEs, 33.7% used ICU interventions on the ward and 87.5% were transferred to a higher level of care. In multilevel modeling, significant independent risk factors for event mortality present at the start of deterioration included patient (disease relapse) and event (e.g., reason for hospital admission, use of ICU intervention on wards, abnormal lactate, platelets, or C-reactive protein, reason for deterioration, and number of organs with dysfunction); hospital factors were not significant predictors of mortality. CONCLUSIONS: Hospitalized pediatric hematology-oncology patients with CDE have high mortality with significant variability across centers. Mortality, however, is largely driven by modifiable event-level factors, demonstrating the need for targeted interventions to improve survival.
Association between NAT10 gene rs8187 G > A polymorphism and Wilms tumor susceptibility in Chinese Han children: a five-center case-control study.
Deng C, Zhu J, Duan F … +9 more , Zhang W, Zhou H, Li S, Zhang J, Cheng J, Fu W, He J, Niu H, Hua RX
BMC Cancer · 2025 Mar · PMID 40098076 · Full text
BACKGROUND: Wilms tumor, a prevalent pediatric kidney cancer, has been extensively studied to elucidate its genetic mechanisms. NAT10 (N-acetyltransferase 10) is a gene encoding acetyltransferase, which is involved in va...
BACKGROUND: Wilms tumor, a prevalent pediatric kidney cancer, has been extensively studied to elucidate its genetic mechanisms. NAT10 (N-acetyltransferase 10) is a gene encoding acetyltransferase, which is involved in various cellular processes, including RNA modification, DNA repair, and protein acetylation. The oncogenic role of NAT10 in cancer has garnered significant attention. However, research on NAT10 genetic variants and their associations with cancer is nascent. METHODS: This study investigated the link between NAT10 genetic variants and Wilms tumor risk via a case‒control design with genomic DNA from 414 patients and 1199 controls. Genotyping was performed via the TaqMan method, and logistic regression statistical analysis was conducted to identify significant associations, followed by extra analysis to minimize false positive significant results. RESULTS: Our findings revealed that the rs8187 G > A polymorphism in the NAT10 gene is significantly correlated with a decreased risk of developing Wilms tumor (GA vs. GG, adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI) = 0.46-0.77, P < 0.0001; GA/AA vs. GG, AOR = 0.74, 95% CI = 0.59-0.93, P = 0.011). Stratified analyses further revealed a significant association in children aged 18 months or under and in subgroups with stage II, stage IV, or combined stage I + II tumors. CONCLUSION: These results highlight the potential of NAT10 rs8187 G > A polymorphism as genetic markers for Wilms tumor susceptibility. This study clarifies the genetic basis of Wilms tumor susceptibility and highlights the role of NAT10 rs8187 G > A polymorphism in early detection and risk assessment.
The effect of online cognitive behavioral therapy for insomnia in adolescents and young adults after childhood cancer: Results from a randomized controlled trial.
van der Hoek H, Peersmann SHM, Maurice-Stam H … +10 more , Kaspers GJL, van den Bergh EMM, Tissing WJE, Kremer LCM, Abbink F, de Vries ACH, Loonen J, van Straten A, Grootenhuis MA, van Litsenburg RRL
Cancer · 2025 Mar · PMID 40045689 · Full text
BACKGROUND: Insomnia is common during and after childhood cancer and associated with negative health outcomes and impaired quality of life. Many adolescents and young adults do not receive treatment. Internet-delivered c...
BACKGROUND: Insomnia is common during and after childhood cancer and associated with negative health outcomes and impaired quality of life. Many adolescents and young adults do not receive treatment. Internet-delivered cognitive behavioral therapy for insomnia (iCBT-i) can fill this gap. This study assesses the effectiveness of the iCBT-i intervention "iSleep youth". METHODS: Patients (12-30 years old) with an Insomnia Severity Index ≥8, ≥6 months after treatment, and <10 years after diagnosis were 1:1 randomized to iSleep youth or the wait list-control group. iSleep youth consists of five online sessions with a coach. Outcomes were sleep efficiency (actigraph-based), insomnia, fatigue, and health-related quality of life (HRQOL). Differences over time between iSleep youth and controls, 3 months (T3) and 6 months (T6) from baseline, were assessed with linear mixed models, controlling for age, sex, and time since end of treatment. iSleep youth also had a follow-up measurement after 12 months (T12). RESULTS: Fifty-four (response rate, 49%) patients participated: 68.9% females, mean age, 18.5 years (SD = 3.5), and mean time since end of treatment 3.8 years (SD = 2.3). No significant effects between the two groups were found for sleep efficiency. However, iSleep youth had a beneficial effect on insomnia severity at T3 (β = -0.79) and T6 (β = -0.55), on fatigue at T3 (β = -1.08) and T6 (β = -0.52) and on HRQOL at T3 (β = 0.46) and T6 (β = 0.62). The scores did not change from T6 to T12 in iSleep youth. CONCLUSIONS: iSleep youth is effective in treating insomnia and concurrent fatigue in adolescents and young adults after childhood cancer and should be implemented.
Development and validation of a predictive model for diagnosing EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis.
Yin Y, Zhang W, Zhao L … +4 more , Li Y, Huang M, Han Y, Wu X
BMC Cancer · 2025 Mar · PMID 40045277 · Full text
PURPOSE: This study aims to identify distinguishing factors between EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis and non-neoplastic EBV-associated hemophagocytic lymphohistiocytosis. Additionally,...
PURPOSE: This study aims to identify distinguishing factors between EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis and non-neoplastic EBV-associated hemophagocytic lymphohistiocytosis. Additionally, we developed and validated a predictive diagnostic model based on these factors. METHODS: To evaluate the early identification of individuals with EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis versus non-neoplastic EBV-associated hemophagocytic lymphohistiocytosis, we carried out a retrospective cohort research. The medical records system included 148 individuals' diagnoses of EBV-associated hemophagocytic lymphohistiocytosis between 2015 and 2023. RESULTS: In this study, 148 patients were included, 75 of whom had non-neoplastic EBV-associated hemophagocytic lymphohistiocytosis and the remaining 73 had EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis. The highest AUC, with a good predictive value, was found for IL-10 > 39.87 pg/ml in separating EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis from non-neoplastic EBV-associated hemophagocytic lymphohistiocytosis. The diagnosis of EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis was influenced by platelets < 33.5*10/L, IL-6 > 20.79 pg/ml, and IFN-γ > 12.12 pg/ml as independent variables. These factors were combined with the predictive value of IL-10 > 39.87 pg/ml to establish the predictive model of the nomogram for diagnosis. The training set's and validation set's areas under the ROC curves were 0.825 and 0.812, respectively, showing that the model had good discrimination, a well-calibrated model, and a clinically valid model as indicated by the clinical decision curve. CONCLUSION: The results of this study showed that the prediction model based on platelets < 33.5*10/L, IL-6 > 20.79 pg/ml, IFN-γ > 12.12 pg/ml, and IL-10 > 39.87 pg/ml could more accurately distinguish between EBER-positive lymphoma-associated hemophagocytic lymphohistiocytosis and non-neoplastic EBV-associated hemophagocytic lymphohistiocytosis. This could aid clinicians in the early detection and convenient individualization of treatment for EBV-associated hemophagocytic lymphohistiocytosis.
Gem-TIP as a salvage therapy for pediatric extracranial malignant rhabdoid tumors: insights from a retrospective case series.
Li J, He L, Hu T … +6 more , Lin X, Zhao Q, Shen Q, Zhou J, Li T, Zhou L
BMC Cancer · 2025 Feb · PMID 40001009 · Full text
OBJECTIVE: This retrospective case series aimed to provide initial insights into the potential effectsof Gemcitabine (Gem), Nab-paclitaxel, Ifosfamide, and Cisplatin (Gem-TIP) combination therapy in children with relapse...
OBJECTIVE: This retrospective case series aimed to provide initial insights into the potential effectsof Gemcitabine (Gem), Nab-paclitaxel, Ifosfamide, and Cisplatin (Gem-TIP) combination therapy in children with relapsed/progressive extracranial malignant rhabdoid tumors (eMRTs). METHODS: A retrospective review of patients treated with Gem-TIP following relapse/progression was conducted. Radiologic responses were assessed using RECIST 1.1 criteria, with supplemental imaging data provided for detailed evaluation. Details of concurrent therapies, including radiotherapy, were documented to better delineate their influence on treatment outcomes. RESULTS: Ten patients were included, with a median age of 29.5 months at diagnosis. Tumor origins were predominantly renal (8 cases). Patients received a median of 3.1 cycles of Gem-TIP. The overall response rate (ORR) was 40% (1 CR, 3 PR), and the disease control rate (DCR) was 70%. Median event-free survival (EFS) and overall survival (OS) were 4 and 7.5 months, respectively. Radiotherapy and secondary surgery administered to 3 patients after Gem-TIP chemotherapy, likely contributed to improved local control. Toxicities included grade 4 neutropenia (50%) and thrombocytopenia (70%). However, limited data on hearing evaluation due to the retrospective design was noted. CONCLUSIONS: Gem-TIP chemotherapy demonstrated preliminary evidence of therapeutic activity in relapsed/progressive eMRTs, but its role requires to be verified by large, prospective multi-center studies of rigorous design.
The effect of oral curcumin on vincristine-induced neuropathy in pediatric acute lymphoblastic leukemia: A double-blind randomized controlled clinical trial.
Eghbali A, Adibifar M, Ghasemi A … +5 more , Afzal RR, Moradi K, Eghbali A, Faress F, Ghaffari K
BMC Cancer · 2025 Feb · PMID 40000988 · Full text
BACKGROUND: Peripheral neuropathy is a major adverse effect of Vincristine (VCR) in pediatric acute lymphoblastic leukemia (ALL) patients. Curcumin can prevent the development of many neurological diseases. METHOD: This...
BACKGROUND: Peripheral neuropathy is a major adverse effect of Vincristine (VCR) in pediatric acute lymphoblastic leukemia (ALL) patients. Curcumin can prevent the development of many neurological diseases. METHOD: This clinical trial study was conducted on 141 pediatric ALL patients, all over 5 years old. The subjects were randomly divided into a curcumin-treatment group and a placebo group. In the curcumin-treatment group, patients received 3 mg/kg oral curcumin capsules twice a day for 3 months. In the placebo cohort, participants were administered placebo capsules twice a day for 3 months. Administration of VCR was started in all patients in both groups, with a weekly dose of 1.5 mg/m. RESULT: Overall, 39.4% of participants in the curcumin treatment group and 70.0% in the placebo group had VIPN. Thus, a significant difference in the incidence of VIPN was observed in the two groups (P < 0.001). A significantly higher frequency of motor nerve abnormalities in all types of nerves was observed in the placebo group than in the curcumin treatment group (P < 0.05). CONCLUSIONS: The results of our study showed that curcumin is effective in preventing the development of VIPN and leads to the improvement of VIPN in these patients. Our findings indicate that the prevalence of VIPN was substantially lower in the curcumin-treated group compared to the placebo group, as confirmed by both NCS and EMG assessments. Furthermore, curcumin demonstrated a protective effect against motor and sensory nerve damage, with a significant reduction in motor nerve abnormalities. TRIAL REGISTRATION: This study was registered at https://irct.behdasht.gov.ir/trial/73161 . TRIAL REGISTRATION NUMBER: IRCT20201107049296N3. Date of registration: 2022-09-11.
Quercetin affects apoptosis and autophagy in pediatric acute myeloid leukaemia cells by inhibiting PI3K/AKT signaling pathway activation through regulation of miR-224-3p/PTEN axis.
Sun J, Sha M, Zhou J … +1 more , Huang Y
BMC Cancer · 2025 Feb · PMID 39984900 · Full text
OBJECTIVE: The aim of this study was to investigate the mechanism by which quercetin (Que) affects apoptosis and autophagy in pediatric acute myeloid leukaemia (AML) cells by inhibiting the activation of the PI3K/AKT sig...
OBJECTIVE: The aim of this study was to investigate the mechanism by which quercetin (Que) affects apoptosis and autophagy in pediatric acute myeloid leukaemia (AML) cells by inhibiting the activation of the PI3K/AKT signaling pathway through the regulation of the miR-224-3p/PTEN axis. METHODS: Blood samples were collected from AML children and healthy volunteers. miR-224-3p and PTEN expression levels were measured. AML cells were pre-treated with Que. MiR-224-3p and PTEN expression levels in AML cells were altered via plasmid transfection. After intervention, PI3K/AKT phosphorylation, AML cell proliferation and apoptosis, concentrations of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in AML cell culture supernatant, apoptosis-related genes Bax and Bcl-2, and autophagy markers LC3-I and LC3-II were tested. The targeting relationship between miR-224-3p and PTEN was identified. RESULTS: MiR-224-3p expression was elevated in AML children, while PTEN was decreased. Que was available to accelerate AML cell apoptosis and restrain its autophagy. Que inhibited miR-224-3p expression and promoted PTEN expression. Upregulating miR-224-3p or downregulating PTEN weakened the effect of Que on AML cell apoptosis and autophagy. MiR-224-3p negatively modulated PTEN expression. Up-regulation of PTEN reversed the effects of up-regulation of miR-224-3p on apoptosis and autophagy in AML cells. In addition, Que inhibited PI3K/AKT signaling pathway activation, while up-regulation of miR-224-3p or down-regulation of PTEN could attenuate the inhibitory effect of Que on PI3K/AKT signaling pathway. Moreover, up-regulation of PTEN reversed the effect of up-regulation of miR-224-3p on the PI3K/AKT signaling pathway. CONCLUSION: Que affects apoptosis and autophagy in pediatric AML cells by inhibiting PI3K/AKT signaling pathway activation through regulation of miR-224-3p/PTEN axis.
Association between TRMT61B gene polymorphism and Wilms tumor susceptibility in Chinese children.
Huang X, Lu J, Deng C … +8 more , Tang W, Wang X, Zhou H, Zhang J, Cheng J, Li S, He J, Ruan J
BMC Cancer · 2025 Feb · PMID 39953499 · Full text
BACKGROUND: Wilms tumor is among the most common pediatric malignant tumors. Although mA modification influences the structure and function of RNA and participates in tumorigenesis, the relationship between mA methyltran...
BACKGROUND: Wilms tumor is among the most common pediatric malignant tumors. Although mA modification influences the structure and function of RNA and participates in tumorigenesis, the relationship between mA methyltransferase TRMT61B gene polymorphisms and Wilms tumor susceptibility is unclear. METHODS: We examined the relationship between TRMT61B gene rs4563180 G > C polymorphism (detected by TaqMan probe method) in 414 children with Wilms tumor and 1199 healthy controls. The relationship between the genotype of each sublayer and the risk of Wilms tumor was studied by stratified analysis. The GTEx database was used to analyze the influence of TRMT61B rs4563180 G > C polymorphism on mRNA expression. RESULTS: The TRMT61B gene polymorphism significantly reduced the susceptibility to Wilms tumor (GC vs. GG: adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.56-0.93, P = 0.012; GC/CC vs. GG: AOR = 0.76, 95% CI = 0.60-0.96, P = 0.021). GC/CC genotype had a protective effect in boys and children with stage III tumors compared with rs4563180 GG genotype. Additionally, the C allele was significantly associated with decreased mRNA expression of TRMT61B gene compared with rs4563180G allele in cultured fibroblasts (P = 3.3e - 80), EBV-transformed lymphocytes (P = 9.5e - 14), and whole blood (P = 6.0e - 12). CONCLUSIONS: Our results confirm that TRMT61B gene is associated with the development of Wilms tumors, but its underlying mechanism requires further exploration.
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