Search Results (629)

Pediatric acute myeloid leukemia (AML) is a highly heterogeneous malignancy, with cytogenetic and molecular abnormalities playing a critical role in determining prognosis and guiding treatment decisions. Despite therapeutic advances, patients with high-risk genetic mutations and translocations continue to experience suboptimal outcomes. As new targeted therapies emerge, the treatment of pediatric AML could undergo a paradigm shift, where “one-size-fits-all” chemotherapy is no longer the only frontline approach. Identifying genetic markers inform risk stratification and have greater impact on shaping the therapeutic approach, including the integration of targeted therapies such as FLT3 and menin inhibitors into frontline therapy. Furthermore, pediatric AML treatment options are being driven by recent discoveries in adult AML, broadening their clinical trials to include pediatric patients, in part due to the RACE for Children Act that went into effect in August 2020. This review identifies the most prevalent high-risk cytogenetic lesions in pediatric AML, emphasizing their incidence, prognostic significance, and implications for clinical management. By synthesizing current research on these key genetic abnormalities and their associated therapies, we aim to provide an updated perspective on the evolving landscape of high-risk pediatric AML management that can then lead to the establishment of an agile framework to rapidly evaluate, approve, and deploy novel agents. Full article

Background/Objectives: Juvenile myelomonocytic leukemia (JMML) is a rare, highly aggressive form of pediatric myelodysplastic/myeloproliferative neoplasm characterized by molecular heterogeneity and constitutive activation of the RAS signaling pathway. This study aimed to characterize the mutational landscape, driver genes, mutational signatures, functional pathways, and therapeutic potential of mutated epigenetic regulator genes in JMML. Methods: Tumor and matched buccal swab samples were collected from 35 JMML patients, and whole-exome sequencing was performed. Somatic variants were called with GATK-Mutect2 and annotated with ANNOVAR. maftools and OncodriveCLUST were used for mutational profiling, co-occurrence analysis, driver gene identification, and protein domain mapping. Drug–gene interactions were explored using DGIdb, mutational signatures for genes were characterized by MutationalPatterns, and functional enrichment analysis was performed by the clusterProfiler package. Results: A total of 28 variants were detected in epigenetic regulator genes, with missense mutations being the most common class of variants and a C>T nucleotide substitution pattern being the most frequent. EP300, SETD2, and DNMT3B were the genes most frequently altered, with 8.57% of cases each, followed by ASXL1, BCORL1, ATRX, KMT2A, and TET2 (5.71% each). Driver gene analysis identified ASXL1 as the top candidate driver gene, followed by BCORL1, EP300, and SETD2. Functional enrichment analysis revealed a high number of genes involved in chromatin organization, histone modification, transcriptional regulation, and oncogenic signaling pathways. The mutational signatures identified were SBS5-like, which are dominated by C>T and T>C transitions, indicating endogenous mutational processes. Analysis of drug–gene interactions revealed KMT2A, EP300, and ATRX as the most interconnected and potentially actionable therapeutic targets. Conclusions: This study provides a comprehensive characterization of epigenetic regulator gene alterations in JMML and highlights the importance of epigenetic dysregulation in disease pathogenesis. Full article

Background/Objectives: Childhood cancer outcomes are influenced by clinical, socioeconomic, and territorial factors, particularly in resource-limited settings. This study characterized pediatric cancer patients from Córdoba and Sucre, Colombia, and evaluated factors associated with clinical outcomes in a regional referral center. Methods: A retrospective hospital-based study included 434 patients aged 0–18 years diagnosed between 2018 and 2024. Sociodemographic, clinical, and territorial socioeconomic variables were analyzed using the Multidimensional Poverty Index (MPI). Clinical outcomes were classified as favorable, non-favorable, or death. Firth-penalized logistic regression models were used to assess adjusted associations. Results: Hematologic malignancies predominated (65.9%), with acute lymphoblastic leukemia as the most frequent diagnosis. Most patients came from municipalities with moderate or high multidimensional poverty (85.2%), and the rural territories of origin showed greater deprivation in education, employment, housing, water access, and sanitation. Favorable outcomes occurred in 82.9% of patients, while 8.5% had non-favorable outcomes and 8.5% died. Older age and non-hematologic malignancies were associated with non-favorable outcomes. Mortality was associated with older age, subsidized health insurance, and non-hematologic malignancies. MPI and rural residence were not independently associated with outcomes after adjustment. Conclusions: Although MPI was not independently associated with clinical outcomes, it identified substantial territorial deprivation. Integrating clinical and territorial indicators may support equity-oriented surveillance and pediatric oncology interventions. Full article

Background: Accurate identification of pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients at increased risk of relapse remains a major clinical challenge, as relapse occurs in 10–20% of cases, including patients initially classified as low- or intermediate-risk. This study aimed to identify clinical, genomic, and measurable residual disease (MRD) related predictors of relapse in pediatric B-ALL. Methods: 51 pediatric patients with B-ALL were included and followed for a median of 30.5 months (IQR, 16–45.5). Patients were stratified according to relapse status. At diagnosis, all cases underwent comprehensive genomic characterization based on the 2022 WHO and ICC classifications, including SNP-array analysis to identify copy number alterations (CNA) involving recurrent B-ALL genes (IKZF1, CDKN2A/B, PAX5, ETV6, BTG1, EBF1, ERG, RB1, and PAR1) and to determine IKZF1^plus status. Clinical variables, including white blood cell count, cytogenetic risk, and MRD assessed by flow cytometry at day 15, day 33, and at the end of induction, were analyzed. Kaplan–Meier and Firth-penalized Cox regression analyses were performed to identify independent predictors of relapse. Results: 86.3% of patients were classified according to the 2022 WHO/ICC classifications, with high hyperdiploidy being the most frequent subtype. During follow-up, 11 patients relapsed. Relapse was significantly associated with high cytogenetic risk (p = 0.007) and showed a trend toward association with an adverse CNA profile (p = 0.075). Patients with >25% bone marrow blasts at day 15 (p < 0.001) and those with positive MRD at the end of induction (p = 0.017) had a significantly higher risk of relapse. In multivariable analysis, high genetic risk and positive end-of-induction MRD remained independent predictors of relapse, with hazard ratios (HRs) of 9.31 (95% CI, 1.55–56.1), p = 0.010, and 10.9 (95% CI, 2.39–49.9), p = 0.002, respectively. Conclusions: An integrated diagnostic strategy including SNP-array provides a high diagnostic yield. High-risk cytogenetic abnormalities and positive end-of-induction MRD are independent predictors of relapse in pediatric B-ALL. Their combined assessment at diagnosis and early treatment may improve risk stratification and may support personalized therapeutic approaches. Full article

Background: Tisagenlecleucel (tis-cel) is the sole chimeric antigen receptor T-cell (CAR-T) therapy approved for pediatric/adolescent relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Infection-related adverse events (IRAEs) represent a leading cause of non-relapse mortality, yet dedicated analysis in patients <18 years remains limited. Objective: This study aimed to analyze the characteristics of IRAEs in pediatric and adolescent patients with r/r B-ALL treated with tis-cel, based on the FDA Adverse Event Reporting System (FAERS) database. The analysis included the reporting proportion, temporal distribution, pathogen spectrum, and overlapping features with other adverse events, generate hypotheses for infection prevention and control in patients aged <18 years. Research Design and Methods: We analyzed FAERS data (August 2017–March 2025) and included 492 cases of <18-year-old r/r B-ALL patients treated with tis-cel. Disproportionality analyses (reporting odds ratio, ROR; information component, IC), time-to-onset analysis, and co-occurrence assessments were performed on 149 infection-related reports. Results: Infection-related AEs occurred in 30.28% of cases, with significantly higher mortality in infected versus non-infected patients (40.27% vs. 12.83%, p < 0.001). Most infections (93.86%) occurred within one month (median time-to-onset = 4 days), peaking within 15 days (77.50%); 2.65% occurred after one year. Significant disproportionate reporting signals were observed for Clostridioides difficile (ROR₀₂₅ = 5.45), influenza virus (ROR₀₂₅ = 7.16), and adenovirus (ROR₀₂₅ = 3.51). Hypogammaglobulinemia (52.94%) and hypoxia (54.90%) exhibited higher co-occurrence with infections than CAR-T-specific toxicities (23.08–35.41%). Conclusions: Infection-related AEs following tis-cel treatment are frequent and associated with significantly increased mortality in pediatric and adolescent r/r B-ALL patients. While most occur early, late infections warrant long-term vigilance. Disproportionality analyses identified signals suggestive of potential high-risk pathogens such as Clostridioides difficile,, influenza, and adenovirus, and hypogammaglobulinemia/hypoxia may serve as early warning indicators. These hypothesis-generating findings require validation in prospective studies. Full article

Background: Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLN-FGFR1), also known as 8p11 myeloproliferative syndrome, are rare and aggressive hematologic malignancies arising from pluripotent stem cells. The FGFR1::ZMYM2 fusion resulting from t(8;13)(p11.2;q12) characteristically co presents as T-lymphoblastic lymphoma in lymph nodes alongside a myeloproliferative neoplasm in the bone marrow. The disease is resistant to tyrosine kinase inhibitors and conventional chemotherapy, and carries a median survival of less than 12 months without allogeneic hematopoietic stem cell transplantation (allo-HSCT). Case Presentation: We report a 23-year-old female who presented with progressive cervical lymphadenopathy and hyperleukocytosis (WBC 186.6 K/μL). Excisional lymph node biopsy demonstrated T-cell acute lymphoblastic lymphoma (T-ALL) with eosinophilic infiltration; immunohistochemistry confirmed lymphoblasts positive for CD1a, CD2, CD3, CD4, CD5, CD7, CD8, and TdT. Concurrent bone marrow biopsy showed a myeloproliferative neoplasm without excess blasts. Chromosomal analysis confirmed t(8;13)(p11.2;q12) with FGFR1::ZMYM2 rearrangement, and NGS identified a concurrent CSF3R variant (Q741*). She received induction chemotherapy per the PEDS AALL1231 protocol (Arm A) followed by consolidation, with a course complicated by hyperleukocytosis, venous thromboembolism, E. coli bacteremia, and severe mucositis requiring PICU admission. Despite initial response, the disease progressed to acute myeloid leukemia (AML) with acquisition of a PTEN variant; the patient was offered but did not complete allo-HSCT and died of refractory AML approximately 10 months after diagnosis. Conclusions: This case highlights the aggressive clinical course and diagnostic challenges of MLN-FGFR1, a rare stem cell-derived myeloid/lymphoid neoplasm. To our knowledge, this appears to be the first reported case documenting sequential CSF3R and PTEN variant acquisition with complete follow-up through fatal AML transformation, and the first to describe treatment with a pediatric ALL induction protocol (PEDS AALL1231) in this setting. The characteristic histomorphologic pattern of eosinophil-rich T-ALL in lymph nodes with concurrent myeloproliferative neoplasm in bone marrow should prompt immediate molecular workup. Allo-HSCT must be pursued urgently at diagnosis, as complications rapidly narrow the transplant window and the disease is uniformly fatal without it. Full article

Background/Objectives: Invasive intracranial pressure (ICP) monitoring is standard in pediatric neurocritical care, but the potential of non-invasive near-infrared spectroscopy (NIRS) and the bedside drivers of ICP remain under-explored. We evaluated the association between cerebral NIRS (rSO₂), pain and agitation, systemic hemodynamics, inflammatory markers, and invasive ICP in critically ill children. Methods: In this prospective pilot study, children undergoing external ventricular-drain-based ICP monitoring were followed with repeated measurements. Linear Mixed Models (LMM) with a random patient intercept were used to assess the NIRS–ICP association, adjusting for hemodynamic (mean arterial pressure (MAP), heart rate) and clinical variables. The Mann–Whitney U test compared parameters across a 20 mmHg ICP threshold, and the Kruskal–Wallis test compared ICP burden across etiology and outcome subgroups. Inflammatory markers (CRP, WBC, procalcitonin) were evaluated separately. Results: A total of 596 measurements from 21 patients were analyzed. Cerebral NIRS was the strongest independent predictor of ICP, showing a significant inverse association (estimate −0.609, p < 0.001). Agitation was independently associated with higher ICP (estimate 0.856, p < 0.001), and this effect was significantly modified by the patient’s behavioral state, being attenuated during sleep and calm wakefulness compared with agitated wakefulness (sleep × agitation interaction, p = 0.002). MAP retained an independent positive association with ICP (estimate 0.044, p = 0.019), whereas pain score did not. After adjustment for etiology and sex, these associations remained unchanged; etiology was itself an independent predictor of ICP (p = 0.001), whereas sex was not. Serum CRP independently predicted ICP (t = 2.382, p = 0.018), whereas WBC and procalcitonin did not. ICP burden differed by etiology, with intracranial masses and leukemia showing the highest loads (p < 0.001), but not across clinical-outcome groups (p = 0.192). Conclusions: Cerebral NIRS-derived rSO₂ was an independent inverse correlate of invasive ICP, and agitation was independently associated with ICP in a state-dependent manner, with its effect attenuated during sleep and calm wakefulness. CRP and etiology further shaped ICP burden. These findings support integrating non-invasive cerebral oximetry into multimodal pediatric neuromonitoring and highlight the value of managing distress to mitigate intracranial hypertension. Full article

Background: Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML) and contributes to leukemogenesis, treatment response, and clinical heterogeneity. While genome-wide methylation studies have identified prognostic methylation signatures, the impact of DNA methylation within pharmacologic pathways and AML-relevant disease genes remains incompletely understood. We investigated the association of DNA methylation in genes of pharmacokinetic/pharmacodynamic (PK/PD) pathways of drugs used to treat AML and in myeloid leukemia-related genes with treatment outcomes in pediatric AML. Methods: DNA methylation profiles from 924 pediatric AML patients treated on Children’s Oncology Group trials (AAML1031, AAML0531, and AAML03P1—available publicly) were analyzed as a discovery cohort. A validation cohort included 159 patients treated on the AML02 trial. A total of 2296 variable CpG sites mapping to 65 PK/PD genes and 107 AML biology/leukemia stemness genes were evaluated. Associations between CpG methylation, gene expression, event-free survival (EFS), overall survival (OS), and measurable residual disease after induction I (MRD1) were assessed using Cox proportional hazards, logistic regression, and correlation analyses. Results: Twenty-three CpG sites in PK/PD genes and forty-two CpG sites in AML-related genes were significantly associated with at least one clinical endpoint after Bonferroni correction (p < 2.17 × 10⁻⁵). Hypermethylation of drug transporters ABCA3, ABCC1, and SLC22A1, as well as pharmacologically relevant genes MPO, NOS3, and CTPS1, was associated with inferior survival and/or increased MRD1 positivity. Among AML biology genes, methylation of ETV6, NOTCH1, RUNX1, KIT, MPL, DNMT3A, and DNMT3B demonstrated consistent associations with outcomes across discovery and validation cohorts. Several genes exhibited significant inverse correlations between DNA methylation and gene expression, including MPO, KIT, MPL, SPINK2, and DNMT3B, supporting functional epigenetic regulation. Notably, hypermethylation of ABCA3, MPO, and MPL was reproducibly associated with poor OS and EFS in both cohorts. Conclusions: DNA methylation of key pharmacologic and leukemia-related genes is associated with clinical outcomes in pediatric AML. These findings identify biologically and clinically relevant epigenetic biomarkers that may improve risk stratification and support the development of precision medicine approaches incorporating DNA methylation profiling and epigenetic therapies in pediatric AML. Full article

Background: Candidemia carries case-fatality rates exceeding 30% in pediatric oncology cohorts from low- and middle-income countries. We describe a temporal cluster of culture-confirmed candidemia cases at King Hussein Cancer Center (KHCC), Amman, Jordan, coinciding with a novel environmental event and the multidisciplinary infection prevention and control (IPC) response undertaken. Methods: This retrospective cohort study describes seven pediatric inpatients with culture-confirmed candidemia identified between June 1 and September 30, 2025, at a 330-bed tertiary oncology center against a background rate of one confirmed case in the preceding six months. An additional five patients with clinically suspected invasive fungal infection (IFI) but negative blood cultures are described separately. Species identification was performed using the BioFire FilmArray Blood Culture Identification (BCID) panel (multiplex PCR); MALDI-TOF MS was additionally available; antifungal susceptibility was determined using the Sensititre system (Thermo Fisher Scientific, UK). Results: The seven confirmed cases comprised six males and one female (median age: 12 years; range: 1–17 years). Underlying diagnoses were predominantly leukemia (71%). All patients had a central venous catheter (CVC) in situ and recent broad-spectrum antibiotic exposure. Candida tropicalis was the predominant species (57%), with azole resistance identified in 42% of tested isolates. A plumbing infrastructure failure with an associated water leak was identified in late August 2025 during the cluster investigation; structural repair was completed in September 2025. The last confirmed case was recorded on 23 September 2025. All patients received guideline-concordant echinocandin- or amphotericin-based therapy. Candidemia-attributable mortality was 14% (1/7). Conclusions: A temporal cluster of seven culture-confirmed candidemia cases—representing a 7-fold increase above background incidence—was identified at a Jordanian pediatric oncology center. The cluster coincided with a documented environmental water leak. Individual single-room isolation, geographic ward sectioning, contact precautions, hand hygiene monitoring, expanded antifungal prophylaxis with real-time protocol adjustment, and environmental remediation were all implemented and documented with defined operational criteria. These data demonstrate that a structured, criteria-driven IPC bundle is operationally feasible at a resource-limited tertiary oncology center. Full article

Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most frequent malignancy of childhood; worldwide, 487,294 new cases and 305,405 deaths were reported in 2022, including more than 5000 new cases in Mexico. Chemotherapy, delivered in induction, consolidation and maintenance phases, remains the mainstay of treatment, yet 10–20% of patients relapse after induction because of chemoresistance, whose molecular basis is still incompletely understood. Methods: This retrospective study aimed to identify proteins associated with resistance to vincristine (VCR) and methotrexate (MTX) administered during the induction phase, using LC–MS/MS proteomics and bioinformatic analysis of treatment-naive bone marrow aspirates from responders and nonresponders. Results: Nonresponders showed a distinct proteomic profile, with deregulated processes converging on cytoskeletal structure and dynamics, nucleic acid metabolism, DNA repair and RNA processing. Within these processes, thymidine phosphorylase (TYMP) and gelsolin (GSN) emerged as differentially expressed proteins, both consistently overexpressed in nonresponders at the individual-patient level. Conclusions: We conclude that cytoskeletal remodeling and nucleotide metabolism are prominent features of intrinsic chemoresistance in pediatric B-ALL, and that TYMP and GSN represent candidate biomarkers of nonresponse to VCR- and MTX-based induction that warrant validation by orthogonal methods in independent, adequately powered cohorts. Full article

Objectives: The importance of sleep disturbance as a component of supportive care in pediatric oncology has recently been recognized, but the characteristics of sleep for this particular disease category have yet to be elucidated. Methods: This cross-sectional study included 54 pediatric patients diagnosed with leukemia or lymphoma and 56 age- and sex-matched clinically stable children attending routine pediatric hematology outpatient follow-up for benign hematological conditions. Sleep was assessed using the Children’s Sleep Habits Questionnaire (CSHQ). Global and domain-specific sleep scores were compared. Multivariable linear regression was used to identify correlates of global sleep disturbance, including parental educational attainment. Within the patient group, recent hospitalization and corticosteroid exposure were modeled separately because of strong collinearity. Results: Patients had higher global CSHQ scores than the comparison group (53.56 ± 8.28 vs. 49.07 ± 8.09, p = 0.005; Cohen’s d = 0.55). Differences were most evident in sleep anxiety and parasomnias (exploratory subscale findings), whereas sleep duration did not differ significantly. In the whole-sample model, patient status (B = 4.16, p = 0.006) and higher parental educational attainment (B = −2.13, p < 0.001) were independently associated with global sleep disturbance. Within the patient group, recent hospitalization was the strongest clinical correlate of sleep burden (B = 11.18, p < 0.001; R² = 0.433). Corticosteroid exposure was associated with higher sleep disturbance only in models excluding hospitalization. Conclusions: Children with leukemia and lymphoma showed a selective parent-reported sleep disturbance pattern characterized mainly by sleep anxiety and parasomnias rather than reduced sleep duration. Recent hospitalization and parental educational attainment appear to be important correlates of sleep burden in pediatric hematology-oncology care. Full article

Background/Objectives: Illness uncertainty is a pervasive psychosocial experience in chronic conditions that is particularly prominent in pediatric oncology. While existing research has explored its psychological impact, a gap remains in understanding how this uncertainty evolves throughout the disease trajectory and how families collectively negotiate and manage this experience over the long term. Methods: This qualitative study was conducted in the hematology ward at a pediatric hospital in Shanghai, China. Using purposive sampling, semi-structured interviews were performed with 32 participants from 12 families of children currently undergoing cancer treatment. Data were collected through in-depth interviews and analyzed using reflexive thematic analysis. The sample was dominated by leukemia cases, with a small number of lymphoma cases; therefore, the findings are most directly transferable to families of children with hematological malignancies. Results: Illness uncertainty is a dynamic and persistent experience permeating the entire pediatric cancer trajectory. Key sources of uncertainty include diagnostic ambiguity and delays, barriers in physician–patient communication, and profound disruptions to family daily life. In response, families proactively develop multidimensional coping strategies: reframing meaning to accept uncertainty, reorganizing family roles and responsibilities, strengthening internal communication, and mobilizing external support networks. These strategies demonstrate both family resilience and inherent vulnerability under sustained pressure. Conclusions: Illness uncertainty in pediatric cancer transcends medical boundaries and is deeply embedded in family life. Healthcare systems should recognize uncertainty as a core experience throughout the disease process and provide family-centered psychosocial and structural support. Strengthening hospital social work services and fostering synergy between peer networks and community resources are essential to enhancing families’ capacity to manage uncertainty and alleviating their long-term psychosocial burden. Full article

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is associated with profound metabolic reprogramming. This exploratory study aimed to characterize the metabolomic profiles of plasma and cerebrospinal fluid (CSF) in children with newly diagnosed pre-B-cell acute lymphoblastic leukemia (pre-B ALL) prior to therapy. Metabolomic analyses were performed using mass spectrometry-based platforms combined with multivariate statistical approaches (PCA, OPLS-DA, SVM-RFE, EBAM). In plasma, we identified 41 significantly altered metabolites (FDR < 0.011), revealing a distinct signature that differentiated pre-B ALL patients from healthy controls. Specifically, patients exhibited elevated levels of hypoxanthine, xanthine, and phosphatidylcholine derivatives, alongside reduced concentrations of L-cysteine and prasterone sulfate, indicating systemic dysregulation of purine, lipid, and amino acid metabolism. In CSF, we observed a distinct metabolic profile characterized by coordinated disturbances in purine degradation, phospholipid metabolism, and sphingolipid pathways. Notably, correlation analysis between the two matrices suggested that systemic metabolic shifts, particularly in purine metabolism (e.g., hypoxanthine and xanthine levels), are mirrored within the central nervous system microenvironment. These findings indicate that children with pre-B ALL exhibit specific metabolic alterations in both compartments before treatment. This work serves as a proof-of-concept for applying metabolomics in pediatric oncology, highlighting the necessity for further validation in larger, prospective cohorts to assess the clinical utility of these profiles. Full article

Background: Juvenile myelomonocytic leukemia (JMML) is a rare RAS/MAPK-driven pediatric myelodysplastic/myeloproliferative neoplasm. The phenotype and survival relevance of NRAS/KRAS alterations remain difficult to interpret because of co-mutations, evolving sequencing, incomplete germline confirmation, and post-diagnostic HSCT. Methods: We retrospectively reviewed 34 children with JMML and classifiable NRAS and/or KRAS alterations diagnosed between November 2010 and September 2022. Patients were classified as NRAS-only, KRAS-only, or NRAS/KRAS co-mutated. Direct comparisons used single-subtype cases. OS was analyzed in evaluable patients, with HSCT modeled as a time-dependent covariate. Results: The cohort included 20 NRAS-only, 12 KRAS-only, and 2 NRAS/KRAS co-mutated cases. KRAS-only cases had higher monocyte percentage (27.2% vs. 16.7%; p = 0.023) and lymphocyte percentage (48.1% vs. 39.0%; p = 0.018), whereas absolute monocyte count was comparable (4.0 vs. 4.0 × 10⁹/L; p = 0.930). PTPN11 was the most frequent non-RAS co-mutation (7/34) and occurred in both NRAS/KRAS co-mutated cases. Methylation status was available in 11 patients and analyzed descriptively. NRAS/KRAS subtype did not significantly stratify OS (HR for KRAS-only vs. NRAS-only, 0.55; 95% CI, 0.18–1.62; p = 0.276). HbF did not significantly stratify OS, while diagnostic total hemoglobin showed only an exploratory univariable association. Exact HSCT dates were retrieved for all 11 transplanted patients; time-dependent Cox analysis showed a significant association between HSCT and better OS (HR, 0.11; 95% CI, 0.02–0.56; p = 0.007). Conclusions: NRAS/KRAS status defined a limited diagnosis-time phenotype but did not independently stratify survival. JMML survival analyses should integrate co-mutations, germline and testing-era limitations, HbF/hemoglobin risk context, and time-dependent HSCT handling. Full article

Background: Febrile neutropenia (FN) is a major complication of chemotherapy in pediatric hematological malignancies. This study compared the efficacy and safety of prophylactic pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) versus daily short-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF). Methods: This single-center, open-label, randomized controlled trial was conducted at a tertiary children’s hospital in China. Pediatric patients (<18 years) with confirmed hematological malignancies (leukemia or lymphoma) were enrolled. A total of 138 chemotherapy cycles were randomized 2:1 to receive either a single dose of PEG-rhG-CSF (100 μg/kg, n = 86 cycles) or daily short-acting rhG-CSF (5 μg/kg/day, n = 45 cycles) after chemotherapy. The primary endpoint was FN incidence. Secondary endpoints included neutropenia incidence, FN duration, time to neutrophil recovery, blood product transfusions, hospital stay, and costs. Safety was assessed by monitoring adverse events (AEs) graded according to NCI CTCAE version 4.03. Results: Baseline characteristics were comparable between groups. PEG-rhG-CSF significantly reduced the incidence of FN (59.3% vs. 77.7%, OR 0.42 (0.18–0.97), p = 0.046) compared to daily rhG-CSF. The median time to neutrophil recovery was 9.8 days (95% CI: 8.1–10.7) in the PEG-rhG-CSF group and 10.3 days (95% CI: 8.6–11.1) in the control group (p = 0.45). No significant differences were observed in FN duration, transfusions, hospital stay, or costs. Subgroup analyses showed PEG-rhG-CSF significantly reduced FN in non-Hodgkin lymphoma (57.4% vs. 83.3%, OR 0.27 (0.08–0.89), p = 0.032). A total of 12 AEs (9.9% overall, mainly bone pain) were observed, with no significant difference between groups and no infection-related deaths. Conclusions: In this single-center, open-label trial, prophylactic single-dose PEG-rhG-CSF was associated with a lower incidence of FN compared to daily short-acting rhG-CSF. Safety profiles appeared broadly similar, but the sample size was insufficient to detect rare differences. Full article