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Background: Most published reports on SAMD9L-related ataxia-pancytopenia syndrome (ATXPC) have emphasized the hematologic findings. Fewer details are known about the progression of neurologic manifestations and methods for monitoring them., Cases: We present six individuals from two families transmitting a heterozygous variant in SAMD9L, exhibiting clinical variations in their hematologic and neurologic findings. Serial motor function testing was used to monitor motor proficiency over a 2 to 3 year period in the proband and his father from Family 1., Conclusions: Our case series focuses on the neurologic progression in patients with heterozygous variants in SAMD9L. Patients with ATXPC should be followed to evaluate a wide range of neurologic manifestations. Serial motor function testing using a standardized method is helpful to track changes in balance and coordination in children and adults with ATXPC and could aid in a future extended natural history study., (© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Epstein-Barr Virus (EBV) is a ubiquitous herpes type virus that is associated with post-transplant lymphoproliferative disorder (PTLD). Usual management includes reduction or cessation of immunosuppression and in some cases chemotherapy including rituximab. However, limited therapies are available if PTLD is refractory to rituximab. Several clinical trials have investigated the use of EBV-directed T cells in rituximab-refractory patients; however, data regarding response is scarce and inconclusive. Herein, we describe a patient with EBV-PTLD refractory to rituximab after orthotopic heart transplantation (OHT) requiring EBV-directed T-cell therapy. This article aims to highlight the unique and aggressive clinical presentation and progression of PTLD with utilization of EBV-directed T-cell therapy for management and associated pitfalls., (© 2024 Wiley Periodicals LLC.)

Background: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia., Methods: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study. Eligible patients (aged >1 year to <18 years) with newly diagnosed Ph-positive acute lymphoblastic leukaemia and performance status of at least 60% received EsPhALL chemotherapy plus dasatinib 60 mg/m 2 orally once daily from day 15 of induction. Patients with minimal residual disease of at least 0·05% after induction 1B or who were positive for minimal residual disease after the three consolidation blocks were classified as high risk and allocated to receive haematopoietic stem-cell transplantation (HSCT) in first complete remission. The remaining patients were considered standard risk and received chemotherapy plus dasatinib for 2 years. The primary endpoint was the 3-year event-free survival of dasatinib plus chemotherapy compared with external historical controls. The trial was considered positive if one of the following conditions was met: superiority over chemotherapy alone in the AIEOP-BFM 2000 high-risk group; or non-inferiority (with a margin of -5%) or superiority to imatinib plus chemotherapy in the EsPhALL 2010 cohort. All participants who received at least one dose of dasatinib were included in the safety and efficacy analyses. This trial was registered with ClinicalTrials.gov, NCT01460160, and recruitment is closed., Findings: Between March 13, 2012, and May 27, 2014, 109 patients were enrolled at 69 sites (including 51 COG sites in the USA, Canada, and Australia, and 18 EsPhALL sites in Italy and the UK). Three patients were ineligible and did not receive dasatinib. 106 patients were treated and included in analyses (49 [46%] female and 57 [54%] male; 85 [80%] White, 13 [12%] Black or African American, five [5%] Asian, and three [3%] other races; 24 [23%] Hispanic or Latino ethnicity). All 106 treated patients reached complete remission; 87 (82%) were classified as standard risk and 19 (18%) met HSCT criteria and were classified as high risk, but only 15 (14%) received HSCT in first complete remission. The 3-year event-free survival of dasatinib plus chemotherapy was superior to chemotherapy alone (65·5% [90% Clopper-Pearson CI 57·7 to 73·7] vs 49·2% [38·0 to 60·4]; p=0·032), and was non-inferior to imatinib plus chemotherapy (59·1% [51·8 to 66·2], 90% CI of the treatment difference: -3·3 to 17·2), but not superior to imatinib plus chemotherapy (65·5% vs 59·1%; p=0·27). The most frequent grade 3-5 adverse events were febrile neutropenia (n=93) and bacteraemia (n=21). Nine remission deaths occurred, which were due to infections (n=5), transplantation-related (n=2), due to cardiac arrest (n=1), or had an unknown cause (n=1). No dasatinib-related deaths occurred., Interpretation: Dasatinib plus EsPhALL chemotherapy is safe and active in paediatric Ph-positive acute lymphoblastic leukaemia. 3-year event-free survival was similar to that of previous Ph-positive acute lymphoblastic leukaemia trials despite the limited use of HSCT in first complete remission., Funding: Bristol Myers Squibb., Competing Interests: Declaration of interests SPH received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen, Servier, and Jazz; received support for travel from Bristol Myers Squibb (BMS) and owns common stock in Amgen. GCaz received funding from BMS to perform molecular testing for AALL1122 patients. AVM received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen. KRS was on advisory boards for Jazz and Novartis. PM-R owns stock in BMS and is an employee of BMS. GCar received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Novartis and Servier; was on an advisory board for Jazz; and received support for attending meetings from Jazz. EAR was on a data and safety monitoring board for Celgene and BMS. MJB received support for the present manuscript from Amgen; and was on an advisory board for Amgen. JMG-F received support for the present manuscript from the National Cancer Institute and BMS. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background The Florida Association of Pediatric Tumor Programs (FAPTP) has used the Statewide Patient Information Reporting System (SPIRS) since 1981 to track all new cases of pediatric cancer. We reviewed the last 40 years of data to see how pediatric cancer care has evolved. Methods We retrospectively analyzed SPIRS data from 1981 through 2020 in five-year increments, looking at numbers of new diagnoses, care delivery sites, and trial enrollment in Children's Oncology Group (COG) studies. Results From 1981-2020 Florida's population increased almost 88% while the pediatric population only grew 61%. New pediatric cancer diagnoses increased 326% to over 1,000 new cases/year. The percentage of patients treated at FAPTP centers grew from 30% to 57% with an annual percentage change (APC) of 10.3% (95% Confidence Interval [CI] of 0.6 to 20.9%). The rate of COG clinical trial enrollment decreased from 32% in 1981-1985 to 20% in 2016-2020, for an APC of 8.91% (95% CI of -13.3 to -4.3%). Conclusions The striking increase in pediatric cancer cases in Florida over the last 40 years was out of proportion to the population growth. More patients received care at FAPTP centers, but a lower percentage were enrolled on COG trials., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shaw et al.)

Purpose: For curative treatment of Hodgkin lymphoma, radiation therapy benefit must be weighed against toxicity. Although more costly, proton radiation therapy reduces dose to healthy tissue, potentially improving the therapeutic ratio compared with photons. We sought to determine the cost-effectiveness of proton versus photon therapy for mediastinal Hodgkin lymphoma (MHL) based on reduced heart disease., Methods and Materials: Our model approach was 2-fold: (1) Use patient-level dosimetric information for a cost-effectiveness analysis using a Markov cohort model. (2) Use population-based data to develop guidelines for policymakers to determine thresholds of proton therapy favorability for a given photon dose. The HD14 trial informed relapse risk; coronary heart disease risk was informed by the Framingham risk calculator modified by the mean heart dose (MHD) from radiation. Sensitivity analyses assessed model robustness and identified the most influential model assumptions. A 30-year-old adult with MHL was the base case using 30.6-Gy proton therapy versus photon intensity modulated radiation therapy., Results: Proton therapy was not cost-effective in the base case for male ($129,000/ quality-adjusted life years [QALYs]) or female patients ($196,000/QALY). A 5-Gy MHD decrease was associated with proton therapy incremental cost-effectiveness ratio <$100,000/QALY in 40% of scenarios. The hazard ratio associating MHD and heart disease was the most influential clinical parameter., Conclusions: Proton therapy may be cost-effective a select minority of patients with MHL based on age, sex, and MHD reduction. We present guidance for clinicians using MHD to aid decision-making for radiation therapy modality., (Copyright © 2021 Elsevier Inc. All rights reserved.)