Journal of Pediatric Hematology/Oncology最新文献

This study evaluates the efficacy and safety of levofloxacin (LVX) prophylaxis against bacteremia and febrile neutropenia in infants under 6 months of age compared with those 6 months to 2 years old with acute myeloid leukemia (AML), relapsed acute lymphoblastic leukemia (rALL), infant ALL (iALL), Down syndrome with ALL (DS ALL), or undergoing hematopoietic stem cell transplantation (HSCT). A retrospective chart review was conducted at Children's Mercy Hospital, Kansas City, MO (April 2019 to September 2024), including 79 encounters from patients receiving LVX prophylaxis. Data were collected on occurrences of bacteremia, febrile neutropenia, and adverse drug reactions. Bacteremia occurred in 9% of patient encounters with no significant difference between the infants under 6 months and the older age group (P=0.643). Secondary outcomes of total duration of treatment antibiotic exposure and increases in liver enzymes were statistically different between groups. However, based on underlying differences in baseline characteristics, the results do not support definitive clinical significance. Other secondary outcomes, including febrile neutropenia, total LVX exposure, and time to first fever, showed no difference between groups. Of 7 positive blood cultures, susceptibility testing for LVX was performed for one culture isolate of Streptococcus mitis, and it was resistant to LVX. This preliminary data indicates that further research is needed in this underexplored topic to confirm these findings with larger patient populations and explore long-term safety in this vulnerable population.

Background and aim: Reactive thrombocytosis is defined as an increase in megakaryocyte count and production secondary to inflammation, malignancy, or anemia. Although cases of reactive thrombocytosis are frequently encountered in newborns admitted to the neonatal intensive care unit (NICU), neonatal thrombocytosis has not yet been fully elucidated. This study aimed to evaluate the maternal and neonatal medical characteristics of neonates diagnosed with reactive thrombocytosis in the NICU.

Materials and methods: This retrospective, cross-sectional study included neonates with thrombocytosis (platelet count >450 × 109/L) who were admitted to our institution's NICU between January 1, 2021, and December 31, 2022. Children with suspected primary thrombocytosis were excluded from the study. Maternal and neonatal medical data were retrospectively analyzed using patient files. The cases were divided into 3 groups: platelet counts >450 and <700 × 109/L, 700 and <900 × 109/L, and 900 and <1000 × 109/L; gestational age was divided into 2 groups: <37 gestational weeks (GH) (preterm) and ≥37 to 42 GH (term); maternal age was divided into 3 groups: 20 years or younger, 20 to 34 years old, and 35 years or older; and birth weight was divided into 3 groups: <2500 g, 2500 to 3999 g, and ≥4000 g. The groups were then compared. Statistical significance was set at P<0.05.

Conclusion: A negative correlation was observed between mean platelet volume (MPV) and hemoglobin (Hb) levels at admission, as well as between MPV and platelet counts. The mean platelet count at the time of thrombocytosis was significantly higher in term cases than in preterm cases. Platelet counts were higher in the macrosomic group than in the nonmacrosomic group. Decreased Hb levels and increased C-reactive protein (CRP) levels were associated with severe thrombocytosis. Reactive thrombocytosis resolved spontaneously without complications and did not require any clinical intervention.

Venous thromboembolism (VTE) is a significant complication in pediatric lymphoma patients, but no validated risk stratification tool exists. In this single-center cohort study, patients aged 18 years or younger with lymphoma were included. A retrospective cohort (N=262) was analyzed for risk factors for symptomatic VTE (sVTE) and prognostic tool development, while a prospective cohort (N=128) was used for validation. sVTE occurred in 8% of the retrospective cohort. Independent risk factors included: mediastinal tumor volume ≥250 mL (OR=4.42, 95% CI: 1.62-12.7), patient transfer to an intensive care unit due to a life-threatening condition within 30 days of admission (ICU+) (OR=4.27, 95% CI: 1.25-13.9), age 12 years or older (OR=7.43, 95% CI: 2.21-34.6), non-O blood type (OR=5.13, 95% CI: 1.5-24.5). A scoring system assigned points as follows: age 12 years or older (1 point), mediastinal mass ≥250 mL (2 points), ICU+ (2 points), and non-O blood group (1 point). A score ≥2 identified high-risk patients (AUC 0.75, sensitivity 0.75, specificity 0.64). The 1-year cumulative incidence of sVTE was 3.9% (95% CI: 0%-8.2%) in non-high-risk versus 18.3% (95% CI: 7.5%-29.2%) in high-risk groups (P=0.008). This validated prognostic tool effectively stratifies thrombosis risk and may guide prophylactic strategies in pediatric lymphoma.

Purpose: Ifosfamide is an alkylating agent used against a variety of pediatric solid tumors; ifosfamide-induced encephalopathy (IIE) is a potential life-threatening event that may occur within 24 to 48 hours after its administration. Hepatic bioactivation of ifosfamide is mediated by CYP3A4 and CYP2B6; their genetic polymorphisms may alter its metabolism, thereby promoting IIE.

Methods: Here we report our experience of a 14-month-old baby affected by rhabdomyosarcoma of the bladder, who developed a severe neurotoxicity after the first dose of ifosfamide and successfully recovered after prompt methylene blue and thiamine administration.

Results: Subsequent genetic analysis revealed homozygosis for CYP2B6 and heterozygosis for CYP3A4. We decided to switch therapy to an alternative alkylating agent such as cyclophosphamide, and he completed the treatment without any notable problems.

Conclusion: IIE is a rare but severe side effect of ifosfamide infusion, and clinical manifestations in children may be misunderstood. We speculate that pharmacogenetic testing may be warranted in very young children to prevent severe IIE.

Background: Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma that, rarely, can present with secondary haemophagocytic lymphohistiocytosis (HLH).

Observations: A 6-year-old boy with ALK-positive ALCL and HLH required intensive care and chemotherapy, experienced multiple relapses, and ultimately achieved remission with crizotinib, ruxolitinib, dexamethasone, and allogeneic stem cell transplant.

Conclusions: This case illustrates the clinical challenges of treating ALK-positive ALCL with concurrent HLH and highlights the role of targeted therapies. As molecular understanding of ALCL increases, integrating novel targeted agents may improve outcomes, particularly in relapsed or high-risk disease.

Background: Mixed autoimmune hemolytic anemia can manifest with severe intra- and extravascular hemolysis, with autoagglutination contributing to vaso-occlusive microangiopathic phenomena.

Observations: We present a case of mixed autoimmune haemolytic anemia with unusually severe cold agglutinin syndrome causing cutaneous, cerebral, ocular, and aural manifestations of microvasculopathy and massive intravascular haemolysis, requiring 6 double-volume whole-blood exchanges over 8 days to temporise severe hemolysis and autoagglutination while immunosuppression with high-dose steroids, rituximab, and bortezomib took effect.

Conclusions: Whole-blood exchange permitted fluid-neutral clearance of preformed antibodies and antibody-coated red cells, with dramatic resolution of microvasculopathy and hemolysis, before discharge home on oral steroid therapy.

Less than half of childhood cancer survivors adhere to recommended follow-up care. We implemented an educational intervention to assess and improve their awareness of long-term follow-up care in pediatric solid and brain tumor survivors or caregivers, using quality improvement methodology. We assessed knowledge of the length of follow-up needed, reasons for recommended lifelong follow-up, and patient-specific late effects. The process was repeated over 3 consecutive visits to assess changes from baseline. Fifty-two patients underwent baseline visits. Twenty-four (22 caregivers, 92%) had 3 visits with the same respondent. From the first to third visit (median: 9.5, range: 6 to 16 mo), correct responses for follow-up duration increased from 29% to 88% ( P <0.001), and for naming at least 2 late effects increased from 71% to 96% ( P =0.04). Forty-five percent reported subjective anxiety after discussion about late effects at the first visit, and 54% rated their anxiety >5 on the 10-point scale. Anxiety levels remained unchanged over time. A structured educational intervention increased awareness of lifelong follow-up care while causing unintended subjective anxiety in cancer survivor caregivers. Comprehensive implementation of this intervention could potentially improve poor long-term follow-up rates in pediatric cancer survivors.

Asparaginase is an established chemotherapeutic agent for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) treatment. Pegylated asparaginase (PEG-Asp) is first-line but may lead to allergic reactions in ∼30% of recipients, leading to substitution by Erwinia -derived asparaginase. Studies demonstrate mixed results on the impact of universal premedication on the incidence of infusion reactions. Our center adopted universal premedication with H1 and H2 antagonists and nadir serum asparaginase activity (SAA) level monitoring in 2019. We assessed the impact of universal premedication on hypersensitivity reactions. We reviewed 107 pediatric ALL/LL patients who received 355 PEG-Asp doses, comparing the frequency of hypersensitivity reactions before universal premedication (PM - ) from 2016 to 2018 and after implementation (PM + ) from 2019 to 2021. No significant difference in reactions was observed between PM - (13 reactions, 27%) and PM + (10 reactions, 17%) patients across all risk stratifications ( P =0.25) or in the severity of reactions. SAA monitoring identified 2 patients (4%) with silent inactivation. The number of Erwinia doses administered between groups did not differ significantly (325 vs. 210, P =0.13). Universal premedication with H1 and H2 antagonists did not impact the number or grade of hypersensitivity reactions to PEG-Asp. We suggest SAA monitoring for patients receiving PEG-Asp to identify silent inactivations.

Background: Neuroblastoma is the most common extracranial solid tumor in children and exhibits substantial clinical heterogeneity. Although key genetic alterations such as N-Myc proto-oncogene protein amplification and anaplastic lymphoma kinase mutations are known drivers of neuroblastoma, their clinical utility is limited by population-specific genetic diversity. To address this, we propose a "function-over-gene" strategy by evaluating extracellular matrix (ECM)-related gene sets as molecular biomarkers, aiming to overcome the limitations posed by genetic heterogeneity and provide novel prognostic insights.

Methods: We integrated data from a single-center cohort and the TARGET database. Cox regression models were used to assess the prognostic value of ECM gene alterations and their association with clinical outcomes. Gene set enrichment analysis (GSEA) was employed to identify ECM-related gene sets, followed by transcriptomic analysis to explore downstream regulatory pathways.

Results: In the single-center cohort, ECM gene mutations were potentially associated with bone and lymph node metastases and emerged as an independent predictor of poor prognosis (HR=2.7, P =0.02) in multivariate analysis. Validation using the TARGET cohort confirmed the prognostic relevance of the ECM gene set (HR=1.55, P =0.0083) and revealed its involvement in modulating the tumor microenvironment via immune and complement pathways.

Conclusion: ECM gene signatures serve as robust prognostic markers across populations. This function-based approach offers a novel perspective to address genetic heterogeneity and provides a theoretical foundation for ECM-targeted combination therapies.