Journal of Pediatric Hematology/Oncology最新文献

Background: The KMT2A rearrangements is primarily caused by balanced translocations, with only a very small fraction resulting from deletions or inversions within the long arm of chromosome 11.

Observations: We present a rare case of KMT2A::NRIP3 fusion-positive B-ALL identified through whole transcriptome sequencing (WTS) resulting from pericentric inversion of chromosome 11. Whole-genome sequencing (WGS) analysis revealed that the breakpoints of the KMT2A::NRIP3 fusion were located deep within intron 8 of KMT2A and intron 1 of NRIP3 , accompanied by a pathogenic hotspot mutation (p.Pro74Leu) in the MYC gene. In addition, we found that NRIP3 may negatively regulate Cyclin D1 ( CCND1 ) in acute myeloid leukemia (AML) but not in B-ALL patients.

Conclusions: The rare KMT2A::NRIP3 fusion gene can be observed not only in pediatric AML patients, but also in B-ALL patients.

Unsupervised machine learning shows significant promise for evaluating multicolor flow cytometry, particularly in advancing minimal residual disease (MRD) analysis. We implemented t-distributed stochastic neighbor embedding (t-SNE)-assisted MRD analysis in a challenging case of Philadelphia chromosome-positive acute lymphoblastic leukemia. This approach enabled us to identify MRD on an unbiased basis with a sensitivity comparable to that of genetic analysis while simultaneously reducing the workload. t-SNE is a valuable tool for the detection and verification of MRD, with its effectiveness significantly enhanced through the integration of optimized antibody panels, data preprocessing, and rigorous back-gating verification.

Hereditary hemochromatosis (HH) is an iron storage disorder characterized by increased iron absorption leading to elevated erythrocyte parameters, including red blood cell (RBC) count. It is the most common genetic disorder in Caucasians and is prevalent in populations with beta-thalassemia. In this study, we retrospectively analyzed the hematological data of 31 pediatric patients with molecularly confirmed HH who were mostly initially suspected of having beta-thalassemia trait (B-TT) due to erythrocytosis. In addition to erythrocytosis, we observed higher-than-expected hemoglobin (Hb) levels for age in these patients. Regardless of low MCV and normal RDW, elevated Hb levels in all patients distinguished them from B-TT cases. Their iron status was normal. These findings suggest that in patients with erythrocytosis and elevated Hb levels, despite other erythrocyte parameters suggestive of B-TT, the possibility of HH should be considered. Since iron overload has not yet developed in pediatric cases, understanding erythrocyte changes is essential for both differential diagnosis and thalassemia eradication.

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 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.

Risk-stratified management with reduced-treatment intensity for standard-risk (SR) patients is an effective strategy. With treatment-related mortality (TRM) continuing to be a major concern in low-middle-income countries, it is vital to limit treatment for patients with favorable disease. We report analysis of 410 consecutive ALL patients from our center treated employing a risk-stratified, response-adapted algorithm. At a median of 8 years from diagnosis, 5-year OS and EFS for the entire cohort and SR group are 84.1%, 81.9%, 91.6%, and 88.5%, respectively. The induction TRM was 1.7% (none in the SR group) reaffirming its efficacy in our setting with relatively limited resources.

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.