Journal of Pediatric Hematology/Oncology最新文献

Mesotheliomas are rare malignancies in the pediatric population. Herein, we describe 3 cases of peritoneal mesothelioma in adolescents in a single institution experience. We review results of the genetic sequencing of the malignancies and highlight how these may differ from findings in adult patients.

Ganglioneuroblastoma intermixed (GNB-I) is a rare pediatric tumor with favorable outcomes when treated primarily with surgical resection. In patients for whom surgical intervention is not feasible, chemotherapy is often considered, although its efficacy remains controversial. This retrospective study examined 12 patients with nonmetastatic GNB-I at Phoenix Children's Hospital. Four patients received chemotherapy but showed no significant tumor reduction postchemotherapy, and all required surgery afterward. Chemotherapy led to notable toxicities, including febrile neutropenia and anaphylactic reaction. These findings suggest chemotherapy offers limited benefit while posing significant risks of cytotoxic adverse events for unresectable GNB-I, and surgery should be prioritized. Further longitudinal studies are needed to confirm these results.

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.

Object: Goal of this study was to investigate distribution of 3 aberrant immunophenotypes of T cells in childhood Hemophagocytic lymphohistiocytosis (HLH), and to find their relations with treatment responses and long-time outcomes.

Methods: Aberrant T cell immunophenotypes presented by patients with HLH at diagnosis during Jan 2018 to Oct 2021 were collected. Distributions of these immunophenotypes among different HLH groups and their relations with first-line therapy responses or lone-time outcomes of patients were studied.

Results: T cell populations with aberrant immunophenotypes were found in 40 patients out of 189 (21.2%). Aberrant immunophenotypic patterns were divided into 3 categories: CD38+HLA-DR+ (N=11, 27.5%), clonal expression of TCRVb (N=17, 42.5%), or down regulation of surface CD5 (N=28, 70.0%). Statistical results showed that T cells from patients with EBV-HLH were prone to present 1 or more of these 3 aberrant immunophenotypes (P<0.001), and that most cases (4/6) with CD4+ T cells with aberrant immunophenotypes were in CAEBV-HLH group. Although plasma levels of IFN-γ were higher in patients with these immunophenotypes (P=0.01), no significant relation was found between these aberrant T cell immunophenotypes and treatment response or long-time outcome. Besides, no hematologic malignancies developed in patients with aberrant T cell immunophenotypes throughout follow up.

Conclusion: Patients with HLH frequently show aberrant immunophenotypes of T cells. In most cases, this immunophenotypic patterns have connection to severity, but not outcome of the disease.

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.