Journal of Pediatric Hematology/Oncology最新文献

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.

Purpose: Given trade-offs between whole-body MRI(WBMRI) techniques' attributes for cancer predisposition syndromes (CPS) surveillance, we determined the strength of preferences of adolescents with no cancer history (group 1) and their parents (group 2) (proxies) for different WBMRI surveillance approaches in CPS.

Methods: A proxy cohort of adolescents without cancer history (group 1) and their parents (group 2) completed a discrete choice experiment (DCE) survey on hypothetical situations of cancer surveillance imaging as if they or their children had a CPS. Five attributes (diagnostic accuracy; examination length; radiation exposure; intravenous access discomfort; and contrast extravasation risk) and 3 WBMRI techniques (inversion recovery [IR]; diffusion-weighted [DW]+IR; positron-emission tomography [PET]-MRI) were assessed in association with respondents' age, sex, education level, and prior MRI history.

Results: There were 86 out of 342 (25.1%) participants; N=71 (83%) females; 21 (24%) adolescents 12 years or older and 18 years or younger, and 65 (76%) parents. Diagnostic accuracy was ranked highest for importance for groups 1 (47.6%) and 2 (55.3%). Group 1 ranked examination length and risk of radiation exposure as second (23.8%) and third (19.0%) preferred attributes, respectively; group 2 ranked these attributes reversely (15.3% and 18.4%). Group 1 ranked intravenous access discomfort and radionuclide extravasation risk as the fourth preferred attribute, 4.8% each, while they were ranked fourth (7.7%) and fifth (3.7%) for group 2. No agreement was reached for aggregated responses (kappa coefficient=0 or McNemar test P>0.05), or any predictors(multinomial logistic regression) between groups 1 and 2.

Conclusion: Although both adolescents and parents agreed on diagnostic accuracy as the most important attribute in CPS imaging surveillance, other preferences were discordant, opening up discussions about whom the clinical decision-making process should align with.

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 cm3. 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.

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 pathophysiological 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.

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. Out 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.

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.

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/mm3) 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.

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.

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 anaemia 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.