No abstract

SARS-CoV-2-induced remission of Hodgkin lymphoma A 61-year-old man was referred to the haematology department with progressive lymphadenopathy and weight loss. He was receiving haemodialysis for end-stage renal failure secondary to IgA nephropathy. He had been off immunosuppressive therapy for three years after a failed renal transplant. Needle-core biopsy of a supraclavicular node demonstrated Epstein-Barr virus (EBV)-positive classical Hodgkin lymphoma [EBV viral polymerase chain reaction (PCR) 4800 copies/ml; log 10 3Á68]. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed avid stage IIIs disease (left image, PET scan, and supplementary image PET/CT). Shortly after diagnosis he was admitted with breathlessness and wheeze and was diagnosed with PCR-positive SARS-CoV-2 pneumonia. After 11 days of best supportive ward-based care he was discharged to convalesce at home. No corticosteroid or immunochemotherapy was administered. Four months later, palpable lymphadenopathy had reduced and an interim PET/CT scan revealed widespread resolution of the lymphadenopathy and reduced metabolic uptake throughout (right image and supplementary image). The EBV viral PCR had also fallen to 413 copies/ml (log 10 2Á62). We hypothesise that the SARS-CoV-2 infection triggered an anti-tumour immune response, as has been described with other infections in the context of high-grade non-Hodgkin lymphoma. 1 The putative mechanisms of action include cross-reactivity of pathogen-specific T cells with tumour antigens and natural killer cell activation by inflammatory cytokines produced in response to infection.

The role of cathepsin L in normal physiological processes was assessed using cathepsin L homozygous knockout mice (B6;129-Ctsl(tm1Alpk)). These mice were generated using gene targeting in embryonic stem cells. Null mice fail to express mRNA and protein to cathepsin L. They developed normally and were fertile. The distinct phenotypic change exhibited was a progressive hair loss, culminating in extensive alopecia by 9 months of age. Histological analysis of the skin from homozygous mice revealed diffuse epithelial hyperplasia, hypotrichosis, hair shaft fragmentation and utricle formation. These findings provide evidence that cathepsin L is involved in the regulation of epithelial cell proliferation and differentiation in the skin. In addition, the role of cathepsin L in bone remodelling was evaluated. Using bone histomorphometric measurements, trabecular, but not cortical, bone volume was found to be significantly decreased in the cathepsin L heterozygote and homozygote mice compared to the wild-type mice. Following ovariectomy, it was observed that loss of trabecular bone, the most metabolically active component of bone, occurred to a lesser extent in homozygote, and heterozygote mice, than was seen in wild-type mice. These observations suggest that cathepsin L is likely to have a role in controlling bone turnover during normal development and in pathological states.

Patients with mantle cell lymphoma progressing on Bruton's tyrosine kinase inhibitor (BTKi) have very poor prognosis and there is currently no standard of care. In this retrospective cohort study, patients progressing on BTKi received R-BAC (rituximab, bendamustine, cytarabine). Overall response rate was 83% (complete response 60%) and 31% were bridged to allogeneic stem cell transplant (alloSCT). Median progression-free survival was 10.1 months (95% confidence interval (CI) 6Á9-13Á3) and median overall survival was 12Á5 months (95% CI 11Á0-14Á0). In those consolidated with alloSCT only one patient relapsed. R-BAC demonstrates a high response rate in the post-BTKi setting and in transplant eligible patients is an effective bridge to alloSCT.