Search Results (178)

The major subtypes of leukemia show sex differences. This review summarizes current knowledge and identifies gaps regarding sex differences across acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphoblastic leukemia in epidemiology, mortality and survival rates, risk factors, and epigenetic, metabolomic, and sex-specific patterns. Males have higher incidence and mortality rates of leukemia compared to females, emphasizing the importance of biological sex. Underreporting of sex differences in leukemia is highlighted, suggesting that sex is often overlooked as a research variable. A significant clinical observation is that women demonstrate higher overall survival rates but experience more severe treatment-related toxicity. Clinically, women tend to survive longer but experience more severe side effects. In contrast, a significant clinical observation in pediatric leukemia contradicts this enigma, suggesting that sex differences may be less pronounced during childhood. These differences play a significant role in how the disease develops. This review presents a sex-based perspective for hematological and biochemical patterns, genetic risk factors, environmental, lifestyle, and parental risk factors, epigenetics and metabolites. Furthermore, males and females might have different responses to the same toxic, environmental, and hormonal exposures. Trying to understand these disparities better based on molecular mechanisms is considered an approach for precision medicine. Full article

(1) Background: Cutaneous secondary malignant neoplasms are a growing survivorship burden after pediatric cancers and hematopoietic stem cell transplantation (HSCT), yet skin-focused surveillance remains inconsistently implemented. (2) Objective: To synthesize current molecular dermatology insights relevant to prevention, early detection, and treatment of basal cell carcinoma (BCC) in high-risk survivors, while anchoring the discussion in a detailed case of multiple BCCs after childhood acute lymphoblastic leukemia and HSCT. (3) Methods: Narrative review integrating clinical, dermoscopic, molecular, and translational data from recent high-impact studies; case retained in full. (4) Results: Radiation exposure (especially total body irradiation), prior immunosuppression, and persistent immune dysregulation synergize with ultraviolet mutagenesis to create a “field cancerization” state characterized by Hedgehog-pathway activation (Patched1/Smoothened), impaired Deoxyribonucleic Acid damage response, and stromal remodeling. Dermoscopy, when embedded in routine whole-body examinations, markedly improves accuracy for keratinocyte cancers. Chemoprevention (e.g., nicotinamide) and targeted therapies (hedgehog inhibitors; Programmed Death-1 blockade) represent key translational levers for care innovation. (5) Conclusions: Integrating structured dermatologic surveillance with molecularly informed prevention and therapy should be standard in survivorship pathways for hematopoietic stem cell transplantation/Radiotherapy-exposed patients. Full article

Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy with promising survival. ALL treatment involves the use of cardiotoxic anthracyclines. The data for children on new methods of echocardiographic detection of early-onset anthracycline-related left ventricle dysfunction is lacking. Methods: Consecutive children with ALL were prospectively enrolled. The echocardiography was performed after ALL diagnosis and before initiation of anthracyclines (first assessment) and after induction and intensification therapy completion (second assessment). The left ventricle echocardiographic assessment involved conventional two-dimensional (2D) echocardiography, 2D speckle tracing, and three-dimensional (3D) echocardiography with offline analysis for 3D speckle tracing. Results: The preliminary group of 32 children presented with mean time between the first and second assessment of 7.3 ± 1.5 months (min.5.3–max.11.4). All children were treated by the same treatment protocol and received doxorubicin and daunorubicin. The mean cumulative equivalent anthracycline dose was 165.6 ± 54.0 mg/m². Statistically significant differences between the first and the second echocardiography were observed in LV-GLS-2D −24.6 ± 3.3% vs. −21.0 ± 3.3%; p < 0.001, LVEF-3D 59.7 ± 7.3% vs. 55.1 ± 3.0%; p = 0.010, LV-GLS-3D −23.3 ± 5.3% vs. −20.4 ± 2.8%; p = 0.031 and LV-GCS-3D −26.3 ± 5.9% vs. −21.9 ± 3.2%; p = 0.017. The differences in LVEF-2D and LV-GRS-3D were not statistically significant. The decrease of >15% from the first assessment was observed in 9 (28%) in LV-GLS-2D, 8 (25%) in LV-GLS-3D, 11 (34%) in LV-GCS-3D and only in 4 (13%) patients in LV-GRS-3D. Conclusions: Two-dimensional and three-dimensional speckle tracing and 3D-LVEF may be sensitive indicators of subclinical left ventricular function impairment in children treated for ALL with anthracyclines. However, this is a preliminary analysis of the planned cohort; our results should be interpreted with caution. Full article

KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL), particularly in infants, represents one of the most aggressive pediatric hematological malignancies with a historically dismal prognosis. While KMT2A-AFF1 (t(4;11)) is the most prevalent fusion, a diverse array of partner genes exists, each conferring distinct biological and clinical features. This review focuses on the rare but clinically significant KMT2A-AFF3 subtype, which arises from the t(2;11)(q11.2;q23) chromosomal translocation. This review summarizes the molecular pathogenesis driven by the KMT2A-AFF3 fusion oncoprotein, which functions as an aberrant transcriptional complex. This complex hijacks essential epigenetic machinery, including the recruitment of DOT1L and interaction with Menin, leading to pathogenic histone modifications (e.g., H3K79 hypermethylation) and the subsequent upregulation of critical target genes, notably the HOXA cluster and MEIS1, thereby enforcing a B-lymphoid differentiation arrest at the pro-B/pre-B stage. Clinically, KMT2A-AFF3 ALL is characterized by high-risk features, including infant onset, hyperleukocytosis, central nervous system (CNS) involvement, and a distinct CD10-negative immunophenotype. This review highlights the evidence defining its poor prognosis, which is primarily driven by profound chemoresistance to conventional therapies, including glucocorticoids. Finally, we discuss the rapidly evolving therapeutic landscape, detailing the limitations of standard intensive chemotherapy and the immense promise of novel targeted strategies, such as Menin inhibitors (e.g., Revumenib), DOT1L inhibitors, and immunotherapies (e.g., CAR-T cells, Blinatumomab), which hold the potential to revolutionize outcomes for this high-risk leukemia subtype. Full article

Background and Objectives: Childhood acute lymphoblastic leukemia (ALL) carries substantial morbidity, mortality, and economic burden, particularly in middle-income countries. The Pediatric Early Warning System (PEWS) is designed to trigger timely escalation of care, yet its independent impact on survival among critically ill leukemic children has not been well defined in Kazakhstan and Central Asia. Materials and Methods: We conducted a retrospective review all ICU admissions for patients aged 0–18 years with ALL at the National Center of Pediatrics, Almaty, across two periods: pre-implementation (January 2020–December 2022) and post-implementation of 24 h PEWS monitoring (September 2023–December 2024). The primary outcome was ICU mortality. Seven domains of covariates—demographic, clinical history, transfusion, vital signs, symptoms, laboratory, and instrumental data—were extracted. Univariable and multivariable logistic regression models were used to assess associations with mortality. Results: Among 255 admissions (105 during PEWS implementation; 150 prior to PEWS implementation), overall ICU mortality was 21.7%. After adjustment, PEWS implementation was not associated with reduced ICU mortality (AOR 0.89), despite a lower unadjusted mortality (15.9% vs. 26.6%). The most clinically relevant secondary findings included strong associations between mortality and bilateral pneumonia (AOR 7.45), ≥4 episodes of hyperthermia within 24 h of ICU admission (AOR 5.42), and systemic inflammatory response syndrome (AOR 4.61). Conclusions: These findings suggest that, within this high-acuity cohort, inflammatory and cardiorespiratory derangements outweigh any potential survival benefit from ward-based PEWS surveillance. Optimizing outcomes will require integrating early warning systems with timely deterioration management, focused cardiopulmonary support, and resource allocation tailored to the clinical context—rather than relying solely on surveillance scores. Full article

Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and while chemotherapy has significantly improved survival rates, it can also lead to long-term side effects, including immune system dysfunction. This study aimed to investigate in detail, using flow cytometry, the T-cell subpopulations in the peripheral blood of children who have completed ALL treatment and compare them to a group of healthy children. The study group consisted of 20 patients, aged 5 to 18 years, with blood samples collected at least one year after treatment completion. Of the 52 T-cell subpopulations analyzed, 16 showed statistically significant differences. Children after ALL treatment had lower absolute values of TCRγδ+ and higher values of double-positive CD4+CD8+ and CD8+ T cells. They also had higher absolute numbers of memory T cells, including total CD45RO+ T cells, and the CD45RO+CD8+ and CD45RO+CD27+ subpopulations. Furthermore, post treatment patients showed higher absolute values of activated T cells (HLA-DR+, HLA-DR+CD8+, HLA-DR+CD57+, and CD25+CD8+), as well as CD57+ and CCR7+ T cells. The absolute leukocyte and granulocyte counts were lower in the study group, while the total lymphocyte count was significantly higher compared to the control group. The findings indicate persistent changes in T-cell subpopulations after ALL treatment, suggesting ongoing immune system rebuilding and chronic antigenic stimulation, possibly due to viral reactivation or chemotherapy-related tissue damage. The increased number of TCRγδ+ cells, which are responsible for eliminating cancer cells, may be a positive aspect of this rebuilding. Full article

Primary cardiac tumors are rare, with an estimated incidence of 0.001% to 0.3% in autopsy series. Most are benign, the most common being cardiac myxomas, which typically originate in the left atrium. Right ventricular myxoma is among the rarest primary cardiac tumors, and its true incidence is difficult to determine, as most data come from isolated case reports. This paper aims to report a case of right ventricular myxoma in a young woman with a history of childhood malignancy and to discuss the possible association between the two conditions. Echocardiography, thoracic computed tomography (CT), and pulmonary CT angiography were used to assess the presence, location, and size of the tumor. The definitive diagnosis was established by histopathological examination. A 34-year-old woman, with a past medical history of acute lymphoblastic leukemia (ALL) in childhood, presented with a dry cough and exertional dyspnea persisting for three weeks. Transthoracic echocardiography revealed a mass located in the right ventricular outflow tract (RVOT), attached near the tricuspid valve and intermittently prolapsing into the pulmonary trunk. CT imaging confirmed the presence of the tumor in the RVOT and the main pulmonary artery. Because of the high risk of massive pulmonary embolism, the patient underwent urgent surgical excision of the tumor. Histopathological analysis confirmed the diagnosis of cardiac myxoma. The postoperative recovery was uneventful, and the three-month follow-up showed no recurrence or signs of pulmonary embolism. The patient’s history of ALL raised the question of a possible association; however, a review of the literature revealed no previously reported link. In conclusion, right ventricular myxomas are extremely rare. The occurrence of cardiac myxoma in this patient following childhood ALL appears to be incidental. Further research is needed to determine whether ALL survivors have an increased predisposition to subsequent cardiac tumors. Full article

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; 30–50% of its cases are caused by the BCR-ABL1 fusion gene as a driver oncogene. In this research work, a study of the cytotoxic properties of phthalimido-1,3-thiazole derivatives against the BCR-ABL protein PDB ID: 4WA9 was carried out using a combination of different computational chemistry methods, including a molecular docking/dynamics study and ADM-T evaluation. Six top hits were identified based on their free energy scores, namely 4WA9-L21, 4WA9-L20, 4WA9-L22, 4WA9-L19, 4WA9-L18 and 4WA9-L18, which demonstrated better binding affinity (from −8.36 to −9.29 kcal/mol). Furthermore, MD studies support the molecular docking results and validate the stability of the studied complexes under physiological conditions. These results confirm that the hits selected are verifiable inhibitors of the BCR-ABL protein, implying a good correlation between in silico and in vitro studies. Moreover, in silico ADME-TOX studies were used to predict the pharmacokinetic, pharmacodynamics, and toxicological properties of the studied hits. These findings support the future role of phthalimido-1,3-thiazole derivatives against the ALL disease and may help to find a new therapeutic combination of drugs to treat relapsed acute lymphoblastic leukemia and improve overall survival. Full article

Background/Objectives: In children developing B-cell acute lymphoblastic leukemia (B-ALL), an immune evasion event takes place where otherwise “silent” preleukemic cells undergo a malignant transformation while escaping immune control, often through unknown mechanisms. Methods and Results: Here, we identify the upregulation of PD-1 expression in preleukemic cells, triggered by Pax5 inactivation in mice and correlating with the time of conversion to leukemia, as a novel marker that favors leukemia evasion. This increase in PD-1 expression is apparent across diverse molecular B-ALL subtypes, both in mice and humans. PD-1 is not required for B-cell leukemogenesis, but, in the absence of PD-1, tumor cells express NK cell inhibitory receptors, highlighting the necessity for leukemic cells to evade the host’s NK immune response in order to exit the bone marrow. PD-1 expression reduces natural antitumor immune responses, but it sensitizes leukemic cells to immune checkpoint blockade strategies in mice and humans. PD-1 targeting confers clinical benefits by restoring NK-mediated tumor cell killing in vitro and eliminating tumor cells in vivo in mice engrafted with B-ALL. Conclusions: These results identify PD-1 as a new therapeutic target against leukemic progression, providing new opportunities for the treatment and possibly also the prevention of childhood B-ALL. Full article

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet diagnosis still relies primarily on invasive bone-marrow procedures and advanced laboratory assays. Non-invasive, rapid, and cost-effective tools remain an unmet need. Fourier-transform infrared (FTIR) spectroscopy has shown promise for detecting cancer-associated biochemical changes in biofluids and cells. Methods: Serum from pediatric ALL patients and controls (n = 103; ALL = 45, controls = 58: healthy = 14, hematology controls = 44 with anemia, thrombocytopenia, leukopenia, and pancytopenia) was analyzed using FTIR. Spectra (800–1800, 2800–3500 cm⁻¹) were preprocessed with baseline correction, derivative filtering, and normalization. Group differences were assessed statistically, and logistic regression with stratified 10-fold cross-validation was applied; Receiver operating characteristic (ROC)\precision–recall (PR) analyses were based on out-of-fold predictions. Results: Distinct spectral alterations were observed between ALL and controls. Leukemia samples showed higher amide I (~1640 cm⁻¹) and amide II (~1545 cm⁻¹) absorbance, lower lipid-related bands (~1450, ~2920 cm⁻¹), and increased nucleic-acid–associated signals (~1080 cm⁻¹). Differences were significant (q < 0.05) with moderate effect sizes. Logistic regression achieved area under the curve (AUC) ≈ 0.80 with sensitivity ~0.73–0.84 across practical decision thresholds (0.50 → 0.30) and higher recall attainable at the expense of specificity. Principal component analysis (PCA)\hierarchical cluster analysis (HCA) indicated partial but consistent group separation, aligning with supervised performance. Conclusions: Serum FTIR spectroscopy shows promise for distinguishing pediatric ALL from controls by reflecting disease-related metabolic changes. The technique is rapid, label-free, and requires only small serum volumes. Our findings represent proof-of-concept, and validation in larger, multi-center studies is needed before clinical implementation can be considered. Full article

Background: Pediatric acute myeloid leukemia (pAML) is the second most common type of childhood leukemia, behind acute lymphoblastic leukemia. High-throughput technologies have enabled the identification of increasing molecular alterations linked to AML prognosis, revealing genomic heterogeneity among individual patients and providing clinically valuable diagnostic and prognostic information. This study systematically analyzed the correlation between high-frequency mutated genes and prognosis in pAML by performing whole-transcriptome sequencing (WTS) of bone marrow samples from newly diagnosed AML children in Southwest China and mapping their genetic profiles. Methods: pAML patients treated at the Department of Hematology and Oncology, Children’s Hospital of Chongqing Medical University, from January 2015 to October 2024, were enrolled, and WTS was performed. The study described the frequency, pathogenicity classification, and risk stratification of mutation genes and fusion genes, and constructed a genetic landscape. For high-frequency pAML mutations, the impact on early induction remission rate (CR) and long-term event-free survival (EFS) was evaluated. Results: A total of 134 pediatric AML patients from Southwest China were included, with a male-to-female ratio of 74:60 and a median diagnosis age of 5.96 years. Based on pathogenicity classification using WTS, fusion genes were categorized into level 1, level 2, and level 3 genes, as well as mutation genes. The study identified five fusion genes of level 1, the most frequent being RUNX1::RUNX1T1 (32/134, 23.88%), KMT2A rearrangements (29/134, 21.64%), and CBFB::MYH11 (13/134, 9.7%). Sixteen mutation genes of level 1 were detected, seven of which recurred in over 5% of patients, including NRAS (31/134, 23.13%), FLT3 (25/134, 18.66%), KIT (24/134, 17.91%), CEBPA (14/134, 10.45%), WT1 (13/134, 9.7%), KRAS (11/134, 8.2%), and PTPN11 (7/134, 5.22%). Sex-based analysis revealed that PTPN11 mutations were significantly more frequent in males (9.45% vs. 0%, p = 0.023), as were KIT mutations (24.32% vs. 10.00%, p = 0.044). Risk-stratified analysis showed that WT1 mutations (14.13% vs. 0%, p = 0.031) and FLT3-ITD mutations (13.19% vs. 0%, p = 0.042) were enriched in intermediate- and high-risk groups, whereas CEBPA (25.64% vs. 5.43%, p = 0.012), KIT (35.90% vs. 10.87%, p = 0.003), and KIT-E8 (20.51% vs. 1.10%, p < 0.001) mutations were more prevalent in low-risk groups. Prognostic analysis indicated that PTPN11 and KIT mutations did not affect CR or EFS across sexes, nor did WT1, CEBPA, or KIT mutations influence outcomes by risk stratification. However, FLT3-ITD-positive patients had significantly lower CRs (χ² value = 11.965, p = 0.007), although EFS differences were nonsignificant. In contrast, WT1 mutations were associated with inferior EFS compared to wild-type (p = 0.036). Furthermore, the univariate and multivariate Cox regression revealed consistent results with the above findings, indicating that WT1 mutation was an independent adverse prognostic factor for EFS (HR = 2.400, 95% CI: 1.101–5.233, p = 0.028). The results of univariate and multivariate logistic regression analyses also confirmed that FLT3-ITD mutation was an independent predictor of initial treatment response in our cohort (OR = 10.699, 95% CI: 2.108–54.302, p = 0.004). Conclusions: This study delineated the genetic landscape of pAML in Southwest China and explored the prognostic value of gene fusions and mutations in early and long-term outcomes. These findings provide a foundation for understanding the genetic heterogeneity of pAML and offer evidence for the development of precision medicine approaches. Full article

Acute lymphoblastic leukemia (ALL) remains the most frequent pediatric malignancy, accounting for approximately 34% of all pediatric cancers, with remarkable improvements in survival (approximately 85%) due to advances in chemotherapy, radiotherapy, and supportive care. However, as survival rates have increased, new challenges have emerged—particularly the growing prevalence of obesity and metabolic syndrome among survivors. This review compiles evidence from the past decade on the relationship between leukemia treatment, obesity, and metabolic risk. The findings indicate that cranial radiotherapy, corticosteroid use, and younger age at diagnosis are key risk factors for excessive weight gain and long-term metabolic disturbances. Genetic factors such as FTO, MC4R, and LEPR polymorphisms may further influence susceptibility to obesity. Nutritional analyses highlight poor diet quality, insufficient micronutrient intake, and high-fat, energy-dense dietary patterns in survivors. Beyond endocrine dysfunction, obesity and metabolic syndrome are associated with elevated cardiovascular morbidity and reduced quality of life. Personalized medicine approaches—integrating genomics, metabolomics, and lifestyle data—hold promise for targeted prevention and intervention strategies. Early detection, continuous metabolic monitoring, and health education remain essential components in the long-term management of childhood leukemia survivors. In this review, we analyzed the dietary patterns of children and long-term leukemia survivors explaining why higher rates of obesity and comorbidities appear during or after treatments, and discussed interventions to prevent these conditions. Full article

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. In Mexico, its higher incidence and lower survival suggest a role for epigenetic factors like DNA methylation (DNAme). We conducted an epigenome-wide association study (EWAS) to define the methylation landscape and identify the profiles associated with ALL and relapse. Bone marrow or peripheral blood samples from pediatric ALL patients at diagnosis and controls without ALL were analyzed using an Infinium MethylationEPIC v2.0 array. Differential methylation was assessed using the ChAMP package. We identified a significant hypermethylated profile in ALL patients compared to controls. Probes in MAD1L1 and RPTOR contained the most differentially methylated CpG sites. Key affected pathways included proliferation, neurotransmission, and neuronal signaling. Survival analysis revealed that hypomethylation of four specific CpGs—cg01052776 (RNH1), cg20747787, cg05001671, and cg01767116 (FBXL22)—was significantly associated with an increased risk of relapse, highlighting their potential as prognostic biomarkers. This study underscores the importance of epigenetic mechanisms in pediatric ALL. Full article

Background/Objectives: Acute leukemias (AL) in children under 1-year-old are combined under the term “infant leukemia” and are a very rare malignancies, accounting for up to 5% of all childhood AL cases. The predominance of unfavorable clinical and laboratory characteristics leads to unsatisfactory treatment results, even with the use of modern treatment protocols. Patients/Methods: A comprehensive search through MEDLINE, PubMed, Scopus, and ScienceDirect using infant leukemia-related keywords was performed and included a final set of 52 academic articles. Our own experience included 11 patients with infant leukemia underwent allo-HSCT (allogeneic hematopoietic stem cell transplantation) at the NN Blokhin National Medical Research Center of Oncology in 2021–2023. Types of leukemia included acute myeloid leukemia, lymphoblastic leukemia, and mixed-phenotype acute leukemia. The most frequent cytogenetic aberration was KMT2A. All patients were in clinical and hematological remission, but four had positive MRD status (minimal residual disease). Donors: haploidentical—5 (45.4%), matched unrelated donor—5 (45.4%), and matched related donor—1 (9.2%). Graft manipulations: post-transplant cyclophosphamide was given to three patients with haplo-HSCT, and TCRαβ/CD19 depletion was performed in two patients. The type of immunosuppressive therapy (IST) varied based on the donor. Conditioning regimens were myeloablative. Results: Median follow-up was 23.5 months. Acute GVHD grade I–II developed in two patients (18%) and grade III–IV in three patients (27%). The overall survival rate was 54.5% (n = 6). The relapse rate after allo-HSCT was 18% (n = 2). The most common cause of treatment failure was infectious complications in the early post-transplant period (70%). Conclusions: Our center’s experience demonstrated acceptable transplant-related mortality and satisfactory relapse rates after allo-HSCT in patients with infant leukemia. The treatment of acute leukemia in infants is challenging, and optimal protocols are being developed around the world specifically for these patients. Taking into account the characteristics of this age group, the choice of chemotherapy drug doses should be carefully considered, and the indications for allo-HSCT should be balanced. Full article

Background: Recent advances in childhood cancer treatment and increased survival rates have led to a growing number of adolescents and young adults (AYAs) who are survivors of childhood cancer (CCSs). This study aimed to examine health status, health-related quality of life (HRQoL), and social outcomes in AYA CCSs. Methods: Sixty-two AYAs who were CCSs (treated within the same tertiary Pediatric Hematology–Oncology Department in Crete, Greece) were enrolled in the study. Self-reported HRQoL was assessed using the Short-Form Health Survey (SF-36). Sixty-five never-ill peers constituted the control group. Results: CCSs reach adolescence and young adulthood without significant deviations in HRQoL from their healthy peers. The presence and severity of late effects were significantly correlated with lower scores in physical health. The cancer type seems to play a pivotal role: Langerhans cell histiocytosis survivors displayed significantly lower scores in mental health, and brain tumor survivors scored substantially lower scores in physical functioning. Acute lymphoblastic leukemia survivors reported the highest scores in mental health. Age at diagnosis of neoplasia was negatively correlated with physical functioning. No significant sex differences were identified. Adherence to multiple healthy lifestyle behaviors (regular exercise, abstaining from alcohol consumption and smoking, and using sun protection) and active employment were correlated with significantly higher scores in mental health. Conclusions: Appropriate therapy and regular follow-up after treatment have led to improved clinical and social outcomes, as assessed by CCSs. More efforts are needed to increase awareness of avoiding harmful behaviors that raise the risk of late effects in this specific group. Full article