Journal of Pediatric Hematology/Oncology最新文献

Post-transplant lymphoproliferative disorders (PTLD) are typically EBV-driven neoplasms that occur after transplantation. Histiocytic sarcomas (HS) are rare malignancies. PTLD HS cases are even rarer. We discuss a case of multiorgan EBV+ HS PTLD in a pediatric male with a history of orthotopic heart transplant. He was initially treated broadly, then narrowed to disease-targeted therapy. Surveillance imaging showed improvement of his diffuse body lesions, but new leptomeningeal enhancements were identified. He developed neurological deterioration and succumbed to his disease. This is a rare case of PTLD manifesting as an EBV-driven HS with meningeal metastasis unresponsive to targeted therapy despite multiorgan improvement elsewhere.

Background: Hematopoietic stem cell transplantation (HSCT) is associated with post-traumatic stress disorder (PTSD), depression, and anxiety in pediatric survivors, but studies on loneliness in these patients remain limited.

Aim: This study aims to explore how PTSD relates to perceptions of loneliness, depression, and anxiety disorders among pediatric HSCT survivors.

Methods: This cross-sectional study included 60 patients who underwent HSCT, 60 patients with various hematological/oncological conditions who did not undergo HSCT, and 65 controls. The Child Post-Traumatic Stress Reaction Index, the UCLA Loneliness Scale, and the Revised Children's Anxiety and Depression Scale were used to assess PTSD, perceptions of loneliness, and depression and anxiety disorders, respectively.

Results: Both HSCT (+) and HSCT (-) groups demonstrated significantly higher PTSD, depression, and anxiety scores compared with the control group. Perceived loneliness was significantly higher in the HSCT (+) group compared with the HSCT (-) and control groups. In addition, a significant positive correlation was observed between PTSD scores and loneliness scores in HSCT (+) and HSCT (-) groups.

Conclusion: Staying in an isolation room during HSCT may be a contributing factor to loneliness and PTSD in pediatric survivors. Early recognition and treatment of PTSD symptoms and addressing loneliness are crucial for effective care during and after HSCT.

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.

Cartilage hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders are rare skeletal dysplasias caused by pathogenic variants in RMRP, associated with immune dysfunction and cancer predisposition. While non-Hodgkin lymphoma is more commonly seen, Hodgkin lymphoma (HL) is rarely reported, and its management in this setting remains unclear. We describe 2 siblings with genetically confirmed CHH-AD who developed relapsed/refractory EBV-positive classic HL. Both presented with short stature, atopy, recurrent infections, and elevated IgE. The brother was diagnosed with stage IV disease, and the sister with stage IIB. Despite receiving frontline chemotherapy, both relapsed within a year. Salvage therapy with gemcitabine/vinorelbine induced metabolic responses, followed by radiotherapy and consolidation with brentuximab vedotin. Autologous transplant was considered but declined by the family due to perceived risks. At 30 months follow-up, both remain in complete remission. Genetic testing confirmed a shared homozygous pathogenic RMRP variant. These cases expand the oncologic spectrum of CHH-AD to include HL, highlight the risk of aggressive disease and early relapse, and demonstrate that durable remission may be achieved without transplantation when consolidation with targeted therapy is feasible. Early recognition of CHH-AD features in HL patients may allow risk-adapted therapy and informed genetic counseling.

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.

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.

Several international studies have reported qualitative alterations in the concentrations of specific trace elements among individuals diagnosed with leukemia. However, further investigations are required to validate these associations and better understand the observed elemental variations. In Karbala province, there is a lack of research addressing the distribution of trace elements in pediatric leukemia cases. The aim of this study was to evaluate the concentrations of selected trace elements (Cd, Pb, Co, Al, Cu) in the blood of children with leukemia in Karbala, and to determine whether these levels differ from the normal reference ranges reported by WHO and NIH guidelines, as well as between urban and rural populations. This study measured the concentrations of cadmium (Cd), lead (Pb), cobalt (Co), aluminum (Al), and copper (Cu) in blood samples collected from 20 children with leukemia at Al-Hussein Medical City Hospital. Atomic absorption spectroscopy (AAS), using both Flame and Graphite Furnace techniques, was used to quantify the levels. The observed concentrations were copper (46.192 to 274.866 ppb), lead (0.767 to 8.675 ppb), cobalt (0.331 to 3.170 ppb), cadmium (0.466 to 1.752 ppb), and aluminum (15.011 to 24.787 ppb). The results indicated that the concentrations of these trace elements were generally lower than the internationally recognized normal ranges. In addition, a geographic variation was observed: children residing in the urban center exhibited lower trace element concentrations compared with those living in rural areas.

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.