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Background: Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy., Methods: We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing., Results: Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39-77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2-62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7-29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4-61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2-62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype., Conclusions: Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

An African American teenage boy during an acute sickle cell crisis spontaneously developed acute bifrontal epidural haematomas (EDHs) in addition to disseminated intravascular coagulation (DIC). The successfully evacuated EDH reaccumulated postoperatively. After multiple transfusions, the patient underwent repeat surgery. Subsequent maximal medical therapy was unable to significantly improve the patient's neurological status, and due to family wishes, care was withdrawn. EDH are the most common emergent neurosurgical complication of sickle cell disease (SCD). Twenty-two such cases have been previously reported. We present one further complicated by DIC leading to reaccumulation of the patient's EDH. An understanding of the mechanisms of EDH formation in SCD and their associated radiological findings could help clinicians identify when a patient is at high risk of EDH formation and thus offer the potential for early intervention prior to the development of an emergency., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Children with hemoglobin SC (HbSC) disease suffer a significant incidence of silent cerebral infarcts but stroke is rare. A 2-year-old African American boy with HbSC disease presented with focal neurologic deficits associated with magnetic resonance imaging evidence of cerebral infarction with vascular abnormalities. After the acute episode he was treated with monthly transfusions and subsequently transitioned to hydroxyurea therapy. The benefits of hydroxyurea as a fetal hemoglobin inducer in HbSC disease, to ameliorate clinical symptoms are supported by retrospective studies. This case highlights the rare occurrence of stroke in a child with HbSC disease and the use of hydroxyurea therapy.

The name of one of the authors in the paper by Kluge et al. [Acta Cryst. (2011), E67, o2143] is corrected.[This corrects the article DOI: 10.1107/S1600536811028947.].