Journal of Pediatric Hematology/Oncology最新文献

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.

Autoimmune hemolytic anemia is a rare immune-mediated disorder characterized by the destruction of red blood cells. Although the IFIH1 gene, which encodes melanoma differentiation-associated protein 5, has been implicated in various autoimmune and immunologic conditions, its involvement in AIHA has not been reported. We describe a 6-year-old boy with AIHA who carries a heterozygous IFIH1 c.2807+1G>A (rs35732034) variant. The patient showed a favorable response to corticosteroid therapy, maintaining remission on low-dose treatment. Functional studies demonstrate that this variant disrupts splice donor sites, resulting in marked impairment of MDA5 activity. This case suggests a possible genetic contribution of the IFIH1 variant to AIHA and highlights the importance of further investigation into its clinical relevance. Our findings expand current knowledge on IFIH1's role in immune regulation and its contribution to autoimmune pathogenesis.

The recombination activating gene 1 (RAG1) is essential for V(D)J recombination and lymphocyte development. While biallelic null RAG1 mutations cause severe combined immunodeficiency (SCID), hypomorphic variants have increasingly been associated with immune dysregulation and hematologic malignancies. This study aimed to present a pediatric case of Epstein-Barr virus (EBV)-negative Burkitt lymphoma carrying a novel homozygous RAG1 variant and to discuss its potential association with immune function and malignancy risk. A 9-year-old Turkish male from a consanguineous family was evaluated for hereditary cancer predisposition. Clinical, immunologic, and genetic assessments were performed, including whole-exome sequencing (WES), Sanger validation, and mRNA expression analysis. The patient presented with cervical lymphadenopathy and was diagnosed with EBV-negative Burkitt lymphoma; he had no recurrent infections, abnormal vaccine reactions, or SCID-related features. Immunologic testing, including lymphocyte subsets and immunoglobulin levels, was within normal limits. WES identified a homozygous RAG1 variant (NM_000448.2:c.460C>T; p.Leu154Phe), predicted to be deleterious and absent from population databases. Both the patient and his healthy dizygotic twin were homozygous, while parents were heterozygous carriers. RAG1 mRNA expression was reduced in heterozygotes but similar in homozygous and wild-type individuals; enzymatic activity was not assessed. The patient responded to chemotherapy and remains in remission under follow-up. In conclusion, this case expands the phenotypic spectrum of hypomorphic RAG1 variants to include EBV-negative Burkitt lymphoma without overt immunodeficiency, suggesting a possible link between partial RAG1 dysfunction and pediatric lymphoma susceptibility.

Osteosarcoma is the most common primary malignancy of bone in children. Stereotactic body radiotherapy (SBRT) is an ablative technique that can overcome radioresistance. The use of SBRT in treating osteosarcoma bone metastases is understudied. Osteosarcoma patients with bony metastases from a single institution were retrospectively reviewed. Treatment response was evaluated per RECIST 1.1 criteria. Adverse effects were evaluated via the Common Terminology Criteria for Adverse Events (CTCAE) grading scale. Thirteen lesions from 9 patients were treated with SBRT. The median time to follow-up was 9.5 months (range 3 to 20.2 mo). Mean pretreatment volume was 48.7 cm 3 . Median delivered dose was 40 Gy in 5 fractions (range 30 Gy in 5 fractions to 48 Gy in 8 fractions). Twelve lesions (92%) showed stable disease (SD). One (8%) lesion showed progressive disease (PD) after 40 Gy in 5 fractions. Local control was 100% at 6 months and 87.5% at 12 months. Pretreatment pain was reported in 78% of patients. Seventy-one percent reported improvement in pain. There were no acute grade ≥3 toxicities observed. SBRT offers promising local control rate in the treatment of osteosarcoma bone metastases with a limited acute side-effect profile. Further studies with a longer follow-up time and larger cohorts are warranted.

Vitamin K deficiency bleeding (VKDB) is a well-known entity in the newborn period, classically presenting during the first week of life. VKDB causing massive bleeding beyond 3 months of age, in an otherwise healthy child, is extremely rare. We present a rare case of massive intracranial bleed in an infant who had received routine vitamin K prophylaxis at birth. His blood investigations revealed severe anemia with a grossly deranged coagulation profile and high proteins induced by vitamin K absence (PIVKAII). His coagulation parameters normalised within 12 hours of Vitamin K and a single dose of FFP. He was a well-nourished child with no evidence of malabsorption. He had no risk factors for VKDB except for extended exclusive breastfeeding. His coagulation profile remained normal at the 6-month review, also. VKDB should be considered outside the typical age group in a child with delayed introduction of complementary feeds.

Measles encephalitis results in devastating epilepsia partialis and/or mortality in the majority of children treated with intense chemotherapy for hematolymphoid malignancies. Although many agents have been studied in the treatment of Measles encephalitis with variable results, there are no effective strategies to mitigate the significant morbidity associated with measles encephalitis till date and treatment has remained largely supportive. In this report, a novel combination of antivirals have been shown to abrogate the morbid sequelae of Measles encephalitis with eventual complete recovery in a child with B-acute lymphoblastic leukemia.

Dengue infection should be considered in the differential diagnosis of febrile neutropenia in endemic areas, even in the absence of warning signs. A retrospective audit was done on medical records of patients (age 14 y or younger) who were diagnosed with dengue fever from April 1, 2023 to March 31, 2024 in a tertiary care cancer center. Patients fulfilling the WHO 2009 criteria of dengue fever and confirmation with detection of either IgM or NS1 were included. Data regarding symptomatology, clinical course, laboratory values, and outcome were analyzed. Twenty-three patients were diagnosed with dengue. Primary malignancy was mainly B-ALL (n=16; 69%). Thirteen patients (56.6%) had criteria fulfilling dengue without warning signs, 5 (21.7%) had dengue with warning signs, and 5 (21.7%) had severe dengue. All patients were treated as inpatients with intravenous fluids and supportive care. Five patients (21.7%) with shock required IVF at 10 mL/kg/h. Two patients (8%) had blood culture positivity and were managed based on the susceptibility pattern. Median delay in chemotherapy was 6 days. The mean duration of hospital stay was 7 days. Three patients (13%) had features of HLH. One patient succumbed to multiorgan failure (with HLH and MDR Klebsiella sepsis).

Background: Timely diagnosis is considered critical in pediatric oncology to optimize treatment outcomes, as delays may impact tumor extension and prognosis. We aimed to assess whether the time to diagnosis and treatment initiation for pediatric patients with rhabdomyosarcoma (RMS) improved over time in Italy and whether longer delays were associated with tumor extension and prognosis.

Methods: We analyzed 749 pediatric patients diagnosed with RMS between 1996 and 2016. Diagnostic interval (DI) was defined as the number of days from symptom onset to diagnosis, while treatment interval (TI) was defined as the time from symptom onset to treatment initiation. DI was correlated with tumor characteristics at diagnosis, and TI was analyzed in relation to survival, using Kaplan-Meier analysis.

Results: The median DI was 32 days, showing a decreasing trend from 39.5 days in 1996 to 2000 to 30 days in 2011 to 2016. A longer DI was associated with age, unfavorable histology, and metastatic disease in univariate analysis, but these were not confirmed in multivariate analysis. The median TI was 48 days. Five-year event-free survival (EFS) and overall survival (OS) were 59.7% and 69.3%. In multivariate analysis, prognosis was negatively associated with age at diagnosis, unfavorable site, nodal involvement, and metastatic disease. TI was not associated with survival.

Conclusions: In our national cohort, the time from symptom onset to diagnosis showed a trend toward shortening in recent years. While a timely diagnosis can provide clarity on the child's condition and potentially reduce parental anxiety, it does not substantially impact tumor characteristics or patient outcomes.

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) with FUS-TFCP2 translocation is a rare, aggressive RMS subtype often involving facial and pelvic bones and showing poor response to standard therapy. The FUS-TFCP2 fusion drives ALK gene activation and overexpression, suggesting ALK as a therapeutic target, though clinical use of ALK inhibitors remains limited in this context. We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

Hepatocellular carcinoma (HCC) is a rare malignancy in children, typically requiring chemotherapy, surgical resection, and/or transplant for treatment. Whether HCC arises as a novel tumor (de novo) or in the setting of chronic liver disease determines treatment strategy. We describe a case of a pediatric patient with unresectable HCC due to macrovascular invasion and tumor thrombus of the portal vein who received transarterial radioembolization (TARE) and underwent successful orthotopic liver transplantation outside of Milan criteria.