Publications by authors named "D Springell"

Introduction: This report outlines the evaluation of physiotherapist-led prehabilitation/rehabilitation for recipients of chimeric antigen receptor T (CAR-T) cell therapy.

Methods: A hybrid approach was used, incorporating in-person assessment of quality of life and functional capacity (6-min walk test and timed sit-to-stand test), and a personalised home exercise programme with remotely delivered physiotherapist support pre/post-admission.

Results: Functional deficits were prevalent at referral for CAR-T.

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Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy.

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Article Synopsis
  • * The study focuses on the risks associated with severe infections in large B-cell lymphoma patients post CAR-T therapy, specifically examining how disease burden and existing complications influence these risks.
  • * Findings suggest that a higher disease burden post-therapy increases infection risk, particularly in patients with multiple infections during treatments like ICANS; the study introduces the concept of "CAR-T cold sepsis" and recommends a strategy for better clinician awareness to minimize non-relapse mortality.
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Chimeric antigen receptor (CAR) T-cell therapy leads to durable remissions in relapsed B-cell cancers, but treatment-associated immunocompromise leads to a substantial morbidity and mortality risk from atypical infection. Mucormycosis is an aggressive and invasive fungal infection with a mortality risk of 40-80% in patients with haematological malignancies. In this Grand Round, we report a case of mucormycosis in a 54-year-old patient undergoing CAR T-cell therapy who reached complete clinical control of Mucorales with combined aggressive surgical debridement, antifungal pharmacotherapy, and reversal of underlying risk factors, but with substantial morbidity from extensive oro-facial surgery affecting the patient's speech and swallowing.

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The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022).

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