Journal of Pediatric Hematology/Oncology最新文献

Malignant transformation of intracranial nongerminomatous germ cell tumors (NGGCTs) is a rare but clinically relevant phenomenon. We present the case of a 13-year-old boy with a localized, pineal NGGCT. After an initial favorable response, tumor growth was noted while still on chemotherapy. Histopathologic characterization revealed that 40% of the tumor was embryonal rhabdomyosarcoma (RMS), consistent with potential malignant transformation. Due to the rare nature of NGGCT malignant transformation, the best clinical approach to these cases remains unclear. We explore existing cases, treatments, and outcomes of malignant transformation in intracranial NGGCTs to help inform future clinical decision-making and the establishment of treatment guidelines.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) can be confused with infantile hemangioma (IH) because of the age of presentation and the presence of a vascular cutaneous lesion. KHE/TA may be complicated by the Kasabach-Merritt phenomenon, a life-threatening condition. MicroRNAs (miRNAs) serve as markers for identifying the pathophysiologic features in several diseases. The purpose of this study was to investigate miRNAs that may be used to differentiate KHE/TA from IH. We selected a set of 20 miRNAs that have been previously reported to be associated with angiogenesis or have been previously reported to be differentially expressed in KHE/TA compared with IH. Quantitative real-time polymerase chain reaction was used to evaluate miRNAs in plasma samples from 12 patients with KHE/TA and 23 patients with IH. Patients with KHE/TA had significantly lower plasma levels of chromosome 19 miRNA cluster (C19MC) miRNAs (miR-517c-3p, miR-518d-5p, miR-519a-3p, and miR-525-5p) compared with patients with IH. No significant correlations were found between the plasma levels of C19MC miRNAs and lesion size in patients with KHE/TA. Plasma levels of C19MC miRNAs may be used to distinguish KHE/TA from IH, which may aid in the management and treatment of patients with KHE/TA.

This study investigated whether preemptive NUDT15 genotyping can reduce episodes of febrile neutropenia during the continuation phase of acute lymphoblastic leukemia (ALL) treatment. This retrospective cohort study enrolled 243 children with ALL who were treated according to the Taiwan Pediatric Oncology Group protocol at the National Taiwan University Hospital. The patients were divided into those who underwent preemptive NUDT15 genotyping (n=30) and historical controls (n=213). Febrile neutropenia episodes were compared between groups stratified by risk classification (standard risk [SR], high-risk [HR], very high-risk [VHR] groups). Multivariate analysis was performed, and the dosage was adjusted for age, sex, and mercaptopurine. Preemptive genotyping did not significantly reduce febrile neutropenia episodes in the SR, HR, and VHR patient groups-although a general trend toward reduction was observed. VHR patients with compound heterozygous NUDT15 polymorphisms had a significantly higher risk (risk ratio: 5.6, P =0.001). Younger age at diagnosis was determined to be a predictor of febrile neutropenia. Preemptive NUDT15 genotyping did not significantly reduce febrile neutropenia episodes in our cohort of pediatric patients with ALL, although it allowed a potential reduction in HR patients. Clinicians should consider preemptive testing, particularly in HR and VHR patient groups, to optimize ALL treatments and reduce adverse events.

We report a case of a 17-year-old male presenting with acute compartment syndrome (CS) of the lower extremity as the initial manifestation of CRLF2-positive, Ph-like B-cell acute lymphoblastic leukemia (B-ALL), without evidence of leukemic infiltration or hematoma. Emergent fasciotomy was performed, followed by cytoreduction with hydroxyurea to allow wound healing before induction chemotherapy. The patient fully recovered and completed induction without complications. This case highlights the importance of recognizing CS as a rare presenting feature of leukemia, and supports hydroxyurea bridging as a viable strategy when immediate chemotherapy is contraindicated to support surgical recovery.

Ewing sarcoma (EWS) is the second most common primary malignant bone and soft tissue tumor. Relapsed EWS is difficult to treat, with poor long-term survival. Isolated lung relapse occurs in about a third of relapsed patients, and there is no standard of care. We aim to review the available literature with the goal of providing guidance for the management of isolated pulmonary relapsed EWS using the 2 major types of pulmonary-directed radiation: whole lung irradiation (WLI) and stereotactic body radiation therapy (SBRT). PubMed and Web of Science were reviewed for studies that evaluated patients with pulmonary relapsed or metastatic EWS who received radiation. Twelve articles met criteria for inclusion; 8 reviewed the use of WLI and 4 reviewed SBRT. Patients who received WLI had improved progression-free survival compared with those who received SBRT, though most had already achieved disease control. There were low rates of toxicity reported with both modalities. WLI appears to be beneficial in patients who have a complete resection before undergoing radiation, while SBRT is indicated to areas of active disease. We suggest future studies test a combination of SBRT in areas of active disease with low-dose WLI to decrease the risk for future metastases.

Background: GNE mutations are rare pathologic conditions that can cause severe thrombocytopenia and bleeding tendency from the neonatal period. The clinical presentation of patients with GNE mutations varies from mild skin and mucosal bleeding to life-threatening bleeding.

Case presentation: This study reported two siblings with hereditary thrombocytopenia. The 2 patients exhibited severe thrombocytopenia (platelet [PLT] count: <15,000/mm 3 ) since the neonatal period and did not respond to intravenous immunoglobulin (IVIG) and steroids. The patients required PLT transfusions once every 1 to 2 weeks due to frequent bleeding incidence. Whole-exome sequencing was performed based on the preliminary diagnosis of inherited thrombocytopenia. A homozygous missense variant (c.1675G>A [p.Gly559Arg]) was detected in GNE . One sibling was unresponsive to the platelet receptor agonists eltrombopag and romiplostim. Meanwhile, the other sibling was unresponsive to eltrombopag but was responsive to romiplostim.

Conclusion: The first-line treatment of patients with GNE mutations is PLT transfusion. However, the management of patients with severe thrombocytopenia and frequent bleeding is challenging. Thrombopoietin receptor agonists are administered to these patients to mitigate the risk of alloimmunization and PLT transfusion refractoriness. However, the observed responses may differ even in siblings carrying the same mutation. This differential response may be related to bone marrow megakaryocyte reserves and hepatocyte Aswell-Morell receptor levels.

Introduction: Ewing Sarcoma (ES) is a small, round, blue cell tumor (SRBCT) characterized by a chromosomal translocation between chromosomes 11 and 22 in ~85% of cases, alongside immunohistochemical (IHC) expression of the surface glycoprotein CD99. Despite advancements in molecular diagnostics, low-income countries continue to face challenges in tumor classification and identification of fusion partners.

Methods: This study retrospectively analyzed pathology reports from 396 patients enrolled in the Latin American Cooperative Group (GALOP) trial, with data collected until December 2021. CD99 positivity or molecular confirmation of EWSR1 translocation were required for inclusion.

Results: IHC marker selection varied across pathology units, reflecting differences in national guidelines. FLI1 was assessed in 45.5% of cases, VIM in 40.4%, and NKX2-2 in 14.9%. The most common complementary markers included desmin (60.1%), myogenin (47.5%), LCA/CD45 (51.5%), and synaptophysin (44.9%). EWSR1 translocation confirmation was performed in 74 patients (18.6%) using FISH and/or PCR. Molecular testing was more frequent in Argentina (73%), while Brazil, Chile, and Uruguay reserved it for diagnostically uncertain cases. Ki-67 was assessed in 70 cases, with most showing a high proliferation index (>30%).

Conclusion: These findings underscore the need for continued collaboration to standardize diagnostic approaches across Latin America, aiming to improve treatment outcomes for ES patients.

Aim: Hematopoietic stem cell transplant (HSCT) remains the cornerstone of treatment in patients with high-risk and relapsed acute myeloid leukemia (AML). In the absence of a fully matched donor, haploidentical HSCT is a feasible option. The aim of this study is to analyze the outcomes of pediatric AML patients, who underwent HSCT at our center.

Methods: This was a retrospective analysis of 48 pediatric patients who underwent 50 transplants at our center from January 2014 to December 2024.

Results: Median age at transplant was 8.5 years, and the male-to-female ratio was 1.9:1. Of 48 children, 46 patients had de novo AML, and 2 had secondary AML. Twenty-nine patients underwent matched sibling donor (MSD), 3 underwent matched related donor (MRD) and the remaining 18 received haploidentical HSCT. All patients received Fludarabine-based conditioning regimens and engrafted. Incidence of acute graft versus host disease (GVHD) in matched donor and haploidentical HSCT was 21.8% and 44.4%, respectively ( P =0.09). Incidence of chronic GVHD was 3.1% in matched donor and 5.5% in haploidentical HSCT ( P =0.72). Cumulative incidence of relapse was 16%. Viral reactivations were seen in 17 patients, cytomegalovirus (CMV) being the commonest. At a median follow-up of 40.9 months, EFS and OS of the overall cohort were 78% and 86%, respectively. Nonrelapse mortality (NRM) was 6%. EFS in matched donor and haploidentical HSCT was 78.1% versus 77.8% ( P =0.78). OS in matched donor and haploidentical HSCT was 84.4% versus 88.9% ( P =0.83). GVHD-free relapse-free survival (GRFS) was 58%. Among the factors analyzed, only pretransplant minimal residual disease (MRD) positivity was found to be associated with significantly poor outcome.

Conclusion: HSCT for children with AML from the developing world shows promising outcomes with high survival rates even in the absence of matched donors. Having expertise in multiple specialties, such as a molecular hematologist, infectious disease (ID), and intensive care specialist, can significantly enhance the outcomes for transplant patients.

Hepatitis-associated aplastic anemia (HAAA) is a rare but potentially life-threatening form of acquired aplastic anemia. Since 2022, our center has observed an increase in HAAA cases. This study examines pediatric HAAA cases to enhance understanding of its presentation, diagnosis, and treatment outcomes, aiming to guide future research and care protocols. A retrospective review was conducted on 5 pediatric HAAA patients treated between 2022 and 2023 at a tertiary children's hospital in the Midwestern United States. Data included clinical presentation, diagnostics, bone marrow and liver pathology, treatments, and clinical course. Immunohistochemical analysis was performed on liver biopsies. As a result, none of the 5 patients developed liver failure. One patient had a genetic mutation associated with an immune-mediated disease; other genetic tests were negative. Histopathology revealed consistent CD8 T-cell infiltration in the liver and bone marrow, with a median CD4/CD8 ratio of 0.5. The median interval from hepatitis onset to pancytopenia was 7 to 9 weeks, with a median follow-up of 2.5 years. Four patients developed severe aplastic anemia (sAA), and 1 had nonsevere aplastic anemia (NSAA). Steroid therapy was insufficient in 4 cases, necessitating antithymocyte globulin (ATG) and cyclosporine. Due to nonresponse, 4 patients required stem cell transplantation (SCT). HAAA can rapidly progress to sAA, highlighting the importance of early, aggressive intervention. Equine ATG and cyclosporine should be initiated promptly, but refractory cases often require SCT. Further research is essential to refine therapeutic strategies and improve outcomes.