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The hook effect is a well-described but clinically underappreciated immunoassay interference, where a falsely lowered result is caused by analyte excess. We describe a situation in which ferritin immunoassay results from a 27-year-old female with immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome were more than 1000 times lower at a reference laboratory than those determined in-house after dilution. This case underscores the importance for clinical care providers to be aware of the impact of the hook effect on ferritin measurements, and to promptly communicate with the laboratory when there are discrepancies between clinical symptoms and test results., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied., Methods: English- or Spanish-speaking patients (ages 8-25 years) undergoing CAR T-cell therapy for any malignancy and their primary caregivers were recruited from Seattle Children's Hospital (SCH), St. Jude Children's Research Hospital (SJCRH), and the Pediatric Oncology Branch of the National Cancer Institute (NCI). Both patient and caregiver completed semi-structured dyadic interviews 3 months post treatment. We used directed content analysis for codebook development and thematic network analysis for inductive qualitative analysis., Results: Twenty families completed interviews (13 patients, 15 parents). Patients were a median age 16.5 years, predominantly female (65%), White (75%), and diagnosed with ALL (75%). Global themes included "A clear decision," "Coping with symptoms," and "Unforeseen psychosocial challenges." When families were asked to describe the "most challenging part of treatment," most described "the unknown." Most reported "the symptoms really weren't that bad," even among patients hospitalized for severe toxicity events. Fatigue, pain, and nausea were the most prevalent symptoms. Importantly, only one family would have chosen a different therapy, if given another opportunity., Conclusions: Although physical symptoms were largely tolerable, recognizing supportive care opportunities remains imperative, particularly psychosocial concerns., (© 2024 Wiley Periodicals LLC.)

Immune-effector cell-associated neurotoxicity syndrome (ICANS) is a significant toxicity occurring with chimeric antigen receptor (CAR) T-cell therapy, with first-line treatment options including supportive care and systemic corticosteroids. Sparse data exist on how to approach progressive/refractory cases of ICANS. We present five pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) who had progressively worsening ICANS despite systemic steroids, and received intrathecal hydrocortisone with rapid reversal of ICANS. Therapeutic lumbar punctures are routinely used in upfront ALL therapy in pediatrics, with a demonstrable safety profile, thus use of intrathecal hydrocortisone merits further prospective studies in patients with severe ICANS., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Serious bacterial infections (SBI) can lead to devastating complications with CD19 CAR T cells and cytokine release syndrome (CRS). Little is known about consequences of and risk factors for SBI with novel CAR T-cell constructs or with CRS complicated by HLH-like toxicities. We report on three patients with B-cell acute lymphoblastic leukemia treated with CD22 CAR T cells who developed SBI and CRS-associated HLH. Serum cytokine profiling revealed sustained elevations well beyond CRS resolution, suggesting ongoing systemic inflammation. Heightened inflammatory states converging with SBI contribute to poor outcomes, and recognition and prevention of extended inflammation may be needed to improve outcomes., (© 2021 Wiley Periodicals LLC.)

Background: Accurate disease detection is integral to risk stratification in B-cell acute lymphoblastic leukemia (ALL). The gold standard used to evaluate response in the United States includes morphologic evaluation and minimal residual disease (MRD) testing of aspirated bone marrow (BM) by flow cytometry (FC). This MRD assessment is usually made on a single aspirate sample that is subject to variability in collection techniques and sampling error. Additionally, central nervous system (CNS) assessments for ALL include evaluations of cytopathology and cell counts, which can miss subclinical involvement., Procedure: We retrospectively compared BM biopsy, aspirate, and FC samples obtained from children and young adults with relapsed/refractory ALL to identify the frequency and degree of disease discrepancies in this population. We also compared CNS FC and cytopathology techniques., Results: Sixty of 410 (14.6%) BM samples had discrepant results, 41 (10%) of which were clinically relevant as they resulted in a change in the assignment of marrow status. Discrepant BM results were found in 28 of 89 (31.5%) patients evaluated. Additionally, cerebrospinal fluid (CSF) FC identified disease in 9.7% of cases where cytopathology was negative., Conclusions: These results support further investigation of the role of concurrent BM biopsy, with aspirate and FC evaluations, and the addition of FC to CSF evaluations, to fully assess disease status and response, particularly in patients with relapsed/refractory ALL. Prospective studies incorporating more comprehensive analysis to evaluate the impact on clinical outcomes are warranted., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Invasive fusariosis (IF) most commonly occurs in patients with hematologic malignancies and severe neutropenia, particularly during concomitant corticosteroid use. Breakthrough infections can occur in high-risk patients despite Aspergillus-active antifungal prophylaxis. We describe a patient with rapid acute lymphoblastic leukemia (ALL) progression who presented with multifocal skin nodules thought to be choloromatous disease. These lesions were ultimately diagnosed as IF and the patient had two simultaneously active disease processes. This case highlights the importance of pathologic diagnosis of new skin lesions in ALL patients, even during leukemia progression, and demonstrates that IF can occur despite normal neutrophil counts and Aspergillus-active prophylaxis., (© 2019 Wiley Periodicals, Inc.)