Semimechanistic pharmacokinetic-pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy.

Tripegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) that has been used to prevent chemotherapy-induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)-pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed-dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK-PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors.

A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification.

Background: We evaluated the therapeutic efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification.

Methods: This study was a multicenter, open-label, single-arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells.

CD19 chimeric antigen receptor T cell therapy in leukemia xenograft mouse: Anti-leukemic efficacy, kinetics, and 4-week single-dose toxicity.

CD19 Chimeric antigen receptor T (CAR-T) cell therapy has shown a promising response rate for relapsed/refractory B-cell malignancies. However, serious side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome arose in early case reports. Though several preclinical and clinical studies of CAR-T cell therapy have been reported, there is a lack of toxicological assessments.

Cryptic KMT2A/MLLT10 fusion detected by next-generation sequencing in a case of pediatric acute megakaryoblastic leukemia.

KMT2A (11q23.3) gene rearrangements are found in acute leukemia and are associated with a poor or intermediate prognosis. MLLT10 is the fourth most common gene fusion partner for KMT2A.

Impact of T-Cell Engagers on COVID-19-Related Mortality in B-Cell Lymphoma Patients Receiving B-Cell Depleting Therapy.

Purpose: B-cell depleting therapies, including T-cell engager (TCE), are increasingly used for patients with hematologic malignancies, including during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the relationship between TCE therapy and COVID-19-related outcomes among patients with COVID-19 and B-cell lymphomas receiving B-cell depleting therapy.

Materials And Methods: This retrospective cohort study included patients with B-cell lymphoma, who were admitted to Seoul Natio-nal University Hospital with COVID-19 between September 2021 and February 2023, and received B-cell depleting therapy before COVID-19 diagnosis.

Tagmentation-based analysis reveals the clonal behavior of CAR-T cells in association with lentivector integration sites.

Integration site (IS) analysis is essential in ensuring safety and efficacy of gene therapies when integrating vectors are used. Although clinical trials of gene therapy are rapidly increasing, current methods have limited use in clinical settings because of their lengthy protocols. Here, we describe a novel genome-wide IS analysis method, "detection of the integration sites in a time-efficient manner, quantifying clonal size using tagmentation sequencing" (DIStinct-seq).

Application of RapidHIT™ ID for cell authentication by fast and convenient STR profiling.

Background: As cell therapies are injected directly into the body, cell authentication is essential. Short tandem repeat (STR) profiling is used for human identification in forensics as well as for cell authentication. The standard methodology (DNA extraction, quantification, polymerase chain reaction, and capillary electrophoresis) takes at least 6 h and requires several instruments to obtain an STR profile.

Computed Tomography-based Prognostication in Lung Adenocarcinomas through Histopathological Feature Learning: A Retrospective Multicenter Study.

Modeling imaging surrogates for well-validated histopathological risk factors would enable prognostication in early-stage lung adenocarcinomas. We aimed to develop and validate computed tomography (CT)-based deep learning (DL) models for the prognostication of early-stage lung adenocarcinomas through learning histopathological features and to investigate the models' reproducibility using retrospective, multicenter datasets. Two DL models were trained to predict visceral pleural invasion and lymphovascular invasion, respectively, using preoperative chest CT scans from 1,426 patients with stage I-IV lung adenocarcinomas.

Response to chemotherapy in juvenile myelomonocytic leukemia and its clinical implications for survival: A retrospective registry-based study of the Korean Pediatric Hematology-Oncology Group.

Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. The chemotherapeutic effect on survival remains unclear, and feasible standardized response criteria are yet to be established. We aimed to evaluate the chemotherapeutic response and its effect on survival in patients with JMML.

Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial.

Background: Sinusoidal obstruction syndrome, also known as veno-occlusive disease, is a potentially life-threatening complication of haematopoietic stem-cell transplantation (HSCT). We aimed to compare defibrotide prophylaxis plus best supportive care versus best supportive care alone for sinusoidal obstruction syndrome prevention after HSCT.

Methods: This open-label, randomised, multicentre, phase 3 trial was done in 104 centres in 14 countries.

Usefulness of two-dimensional shear wave elastography in diagnosing hepatic veno-occlusive disease in pediatric patients undergoing hematopoietic stem cell transplantation.

Purpose: This study aimed to evaluate the usefulness of two-dimensional shear wave elastography (2D-SWE) in diagnosing hepatic veno-occlusive disease (VOD) in pediatric patients.

Methods: This study retrospectively included pediatric patients who underwent hematopoietic stem cell transplantation (HSCT) between November 2019 and January 2021. All 34 patients (8.

Medulloblastoma: Current Perspectives and Recent Advances.

Medulloblastoma is the most common embryonal tumor of the central nervous system in childhood. Combined multimodality approaches, including surgery, radiation, and chemotherapy, have improved the outcome of medulloblastoma. Advances in genomic research have shown that medulloblastoma is not a biologically or clinically discrete entity.

Comparison of the clinical features and treatment outcomes of pilocytic astrocytoma in pediatric and adult patients.

Purpose: Pilocytic astrocytoma is a slow-growing tumor that predominantly develops in children, but has a broad age spectrum. A notable characteristic of pilocytic astrocytoma is that the tumor arises in diverse locations and the clinical course is not always benign. Therefore, it is necessary to elucidate the clinical spectrum of the disease and analyze the relevant prognostic factors.

Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial.

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI.

Distinct and overlapping features of nodal peripheral T-cell lymphomas exhibiting a follicular helper T-cell phenotype: a multicenter study emphasizing the clinicopathological significance of follicular helper T-cell marker expression.

Nodal peripheral T-cell lymphoma (PTCL) is a heterogeneous category including angioimmunoblastic T-cell lymphoma (AITL), PTCL of follicular helper T-cell (Tfh) phenotype (PTCL-Tfh), and PTCL, not otherwise specified (PTCL-NOS). We explored Tfh marker profiles in nodal PTCL. Nodal PTCLs (n = 129) were reclassified into AITL (58%; 75/129), PTCL-Tfh (26%; 34/129), and PTCL-NOS (16%; 20/129).

Feasibility of low-dose radiotherapy for patients with stage I/II extranodal NK-/-cell lymphoma, nasal type achieving complete response after l-asparaginase-containing chemotherapy.

Purpose: To assess treatment outcomes in patients with stage I/II extranodal NK-/-cell lymphoma, nasal type (ENKTCL-NT) and the feasibility of low-dose radiotherapy (RT) for achieving complete response (CR, defined as showing no residual hypermetabolic uptake on positron emission tomography [PET] or no residual lesions on computed tomography [CT]) after l-asparaginase-containing chemotherapy (l-ASP).

Materials And Methods: Between 1992 and 2018, 76 patients with early-stage ENKTCL-NT who achieved CR or partial response (PR) after induction chemotherapy received adjuvant RT. RT doses (using biologically equivalent doses in 2 Gy fractions [EQD2]) and rates of local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and cancer-specific survival (CSS) were determined.

Transcriptional upregulation of CXCL13 is correlated with a favorable response to immune checkpoint inhibitors in lung adenocarcinoma.

Background: The chemokine CXCL13 is known to influence local anti-tumor immunity by recruiting immune cells and forming tertiary lymphoid structures (TLS). It has been hypothesized that TLS, led by the expression of CXCL13, could be a predictive or prognostic biomarker for immunotherapy. We investigated the predictive value of CXCL13 to immune checkpoint inhibitors (ICI) in lung adenocarcinoma.

Relative infectivity of the SARS-CoV-2 Omicron variant in human alveolar cells.

With the continuous emergence of highly transmissible SARS-CoV-2 variants, the comparison of their infectivity has become a critical issue for public health. However, a direct assessment of the viral characteristic has been challenging because of the lack of appropriate experimental models and efficient methods. Here, we integrated human alveolar organoids and single-cell transcriptome sequencing to facilitate the evaluation.

High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration.

Background: Relationship between cancer cell glycolysis and the landscape of tumor immune microenvironment in human cancers was investigated.

Methods: Forty-one fresh lung adenocarcinoma (ADC) tissues were analyzed using flow cytometry for comprehensive immunoprofiling. Formalin-fixed tissues were immunostained for hexokinase-2 (HK2) to assess cancer cell glycolysis.

Clinical Characteristics and Prognosis of the Modified Probable Pneumonia in Korean Children, 2001-2021.

There are few data about pneumonia (PCP) in children, particularly in developed countries. This study investigated the clinical characteristics and prognosis of the clinical PCP in non-HIV-infected Korean children. Children with positive results for the staining and/or polymerase chain reaction (PCR) for between 2001 and 2021 were identified.

Treatment pathways and clinical outcomes in Hodgkin lymphoma outside Europe and North America: results from the international, multicenter, retrospective, B-HOLISTIC study.

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB-IV classical HL receiving frontline treatment ( = 1598) or relapsed/refractory HL (RRHL,  = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group.

Favorable outcome of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with nonmetastatic osteosarcoma and low-degree necrosis.

Background: A low-degree tumor necrosis after neoadjuvant chemotherapy is a poor prognostic factor for osteosarcoma (OSA). However, the role of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation in OSA remains controversial. We analyzed the treatment outcomes and prognostic factors of nonmetastatic OSA and compared the HDC and conventional chemotherapy (CC) outcomes of patients with <90% necrosis after neoadjuvant chemotherapy.

Allogeneic hematopoietic cell transplantation in patients with juvenile myelomonocytic leukemia in Korea: a report of the Korean Pediatric Hematology-Oncology Group.

Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. This multicenter study evaluated the characteristics, outcomes, and prognostic factors of allogeneic hematopoietic cell transplantation (HCT) in recipients with JMML who were diagnosed between 2000 and 2019 in Korea. Sixty-eight patients were retrospectively enrolled-28 patients (41.