The Prognostic Value of Eight Immunohistochemical Markers Expressed in the Tumor Microenvironment and on Hodgkin Reed-Sternberg Cells in Pediatric Patients With Classical Hodgkin Lymphoma

Immunohistochemical markers are associated with treatment outcome in adults with classical Hodgkin Lymphoma (cHL). Studies in children are scarce and inconsistent. We investigated in 67 children with cHL, whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and TARC at diagnosis is associated with disease free survival (DFS) and with interim remission status. Low CD15 and low TARC expression were associated with relapsed disease. Low expression of PD-L1 was associated with complete remission at interim PET-scan. Our data suggest a difference between pediatric and adult cHL. This underlines the importance of future research into specific prognostic factors in pediatric cHL, indispensable for improvement of treatment in this population

Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma

While cervical lymphadenopathy is common in children, a decision model for detecting high-grade lymphoma is lacking. Previously reported individual lymphoma-predicting factors and multivariate models were not sufficiently discriminative for clinical application. To develop a diagnostic scoring tool, we collected data from all children with cervical lymphadenopathy referred to our national pediatric oncology center within 30 months (n = 182). Thirty-nine putative lymphoma-predictive factors were investigated. The outcome groups were classical Hodgkin lymphoma (cHL), nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), non-Hodgkin lymphoma (NHL), other malignancies, and a benign group. We integrated the best univariate predicting factors into a multivariate, machine learning model. Logistic regression allocated each variable a weighing factor. The model was tested in a different patient cohort (n = 60). We report a 12-factor diagnostic model with a sensitivity of 95% (95% CI 89–98%) and a specificity of 88% (95% CI 77–94%) for detecting cHL and NHL. Our 12-factor diagnostic scoring model is highly sensitive and specific in detecting high-grade lymphomas in children with cervical lymphadenopathy. It may enable fast referral to a pediatric oncologist in patients with high-grade lymphoma and may reduce the number of referrals and unnecessary invasive procedures in children with benign lymphadenopathy.</p

Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma

While cervical lymphadenopathy is common in children, a decision model for detecting high-grade lymphoma is lacking. Previously reported individual lymphoma-predicting factors and multivariate models were not sufficiently discriminative for clinical application. To develop a diagnostic scoring tool, we collected data from all children with cervical lymphadenopathy referred to our national pediatric oncology center within 30 months (n = 182). Thirty-nine putative lymphoma-predictive factors were investigated. The outcome groups were classical Hodgkin lymphoma (cHL), nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), non-Hodgkin lymphoma (NHL), other malignancies, and a benign group. We integrated the best univariate predicting factors into a multivariate, machine learning model. Logistic regression allocated each variable a weighing factor. The model was tested in a different patient cohort (n = 60). We report a 12-factor diagnostic model with a sensitivity of 95% (95% CI 89–98%) and a specificity of 88% (95% CI 77–94%) for detecting cHL and NHL. Our 12-factor diagnostic scoring model is highly sensitive and specific in detecting high-grade lymphomas in children with cervical lymphadenopathy. It may enable fast referral to a pediatric oncologist in patients with high-grade lymphoma and may reduce the number of referrals and unnecessary invasive procedures in children with benign lymphadenopathy

Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype

Neuroblastoma is the most common extracranial solid tumor and accounts for ∼10% of pediatric cancer-related deaths. The exact cell of origin has yet to be elucidated, but it is generally accepted that neuroblastoma derives from the neural crest and should thus be considered an embryonal malignancy. About 50% of primary neuroblastoma tumors arise in the adrenal gland. Here, we present an atlas of the developing mouse adrenal gland at a single-cell level. Five main cell cluster groups (medulla, cortex, endothelial, stroma, and immune) make up the mouse adrenal gland during fetal development. The medulla group, which is of neural crest origin, is further divided into seven clusters. Of interest is the Schwann cell precursor (“SCP”) and the “neuroblast” cluster, a highly cycling cluster that shares markers with sympathoblasts. The signature of the medullary SCP cluster differentiates neuroblastoma patients based on disease phenotype: The SCP signature score anticorrelates with ALK and MYCN expression, two indicators of poor prognosis. Furthermore, a high SCP signature score is associated with better overall survival rates. This study provides an insight into the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype

Central venous catheter–associated complications in pediatric patients diagnosed with Hodgkin lymphoma: implications for catheter choice

Purpose: The purpose of this study was to determine the most optimal central venous catheter (CVC) for pediatric patients with Hodgkin lymphoma (HL) in terms of complications. Methods: A retrospective study including patients diagnosed with HL from 2015 to 2021 at the Princess Máxima Center was performed. Patients were followed from CVC insertion until removal or 06–2021, whichever came first. The primary outcome was the CVC-related complication incidence rate (IR) per 1000 CVC-days. Furthermore, the incidence rate ratio (IRR) was calculated by comparing complication IRs between peripherally inserted central catheters (PICC) and totally implantable venous access ports (TIVAP). Additionally, risk factors for central venous thrombosis (CVT) were identified. Results: A total of 98 patients were included. The most frequently observed complications were local irritation/infections (18%; IR 0.93), malfunctions (15%; IR 0.88), and CVC-related CVTs (10%; IR 0.52). Single lumen PICCs were associated with a higher risk of complications (49% vs. 26%; IRR 5.12, CI95% 2.76–9.50), severe complications (19% vs. 7%; IRR 11.96, CI95% 2.68–53.42), and early removal (18% vs. 7%; IRR 9.96, CI95% 2.18–45.47). A single lumen PICC was identified as a risk factor for CVC-related CVT when compared to TIVAPs (12% vs. 7%, IRR 6.98, CI95% 1.45–33.57). Conclusion: The insertion of a TIVAP rather than a PICC should be recommended for pediatric patients with HL, especially in the presence of CVT-related risk factors. Future trials should evaluate the efficacy and safety of direct oral anticoagulants for the primary prevention of CVT in pediatric patients with a PICC and other CVT-related risk factors

Improved survival for adolescents and young adults with Hodgkin lymphoma and continued high survival for children in the Netherlands: a population-based study during 1990–2015

Population-based studies that assess long-term patterns of incidence, major aspects of treatment and survival are virtually lacking for Hodgkin lymphoma (HL) at a younger age. This study assessed the progress made for young patients with HL (<25 years at diagnosis) in the Netherlands during 1990–2015. Patient and tumour characteristics were extracted from the population-based Netherlands Cancer Registry. Time trends in incidence and mortality rates were evaluated with average annual percentage change (AAPC) analyses. Stage at diagnosis, i

NOTCH1 fusions in pediatric T-cell lymphoblastic lymphoma: A high-risk subgroup with CCL17 (TARC) levels as diagnostic biomarker

Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high-risk T-LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T-LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018 and 2023, we discovered a previously unknown high-risk biological subgroup of children with T-LBL. This subgroup is characterized by NOTCH1 gene fusions, found in 21% of our T-LBL cohort (6/29). All patients presented with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Blood CCL17 (C-C Motif Chemokine Ligand 17, TARC) levels were measured at diagnosis in 26/29 patients, and all six patients with NOTCH1 gene fusions patients exclusively expressed highly elevated blood CCL17 levels, defining a novel and previously not known clinically relevant biomarker for T-cell lymphoblastic lymphoma. Four out of these six patients relapsed during therapy, a fifth developed a therapy-related acute myeloid leukemia during maintenance therapy. These data indicate that T-LBL patients with a NOTCH1 fusion have a high risk of relapse which can be easily identified using a blood CCL17 screening at diagnosis. Further molecular characterization through NOTCH1 gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies