Biclonal lymphoproliferative disorders: another association with NOTCH1- mutated chronic lymphocytic leukaemias
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ORIGINAL ARTICLE
Biclonal lymphoproliferative disorders: another association with NOTCH1-mutated chronic lymphocytic leukaemias Helen Fogarty 1,2,3 & Anita Dowling 1,2 & David O’Brien 2 & Steve Langabeer 1 & Christopher Laurence Bacon 2 & Richard Flavin 4 & Michael O’Dwyer 5 & Brian Hennessy 6 & Hilary O’Leary 7 & Gerard Crotty 8 & Robert Henderson 8 & James Nolan 7 & Patrick Thornton 9 & Elisabeth Vandenberghe 1,2 & Fiona Quinn 1 Received: 9 August 2019 / Accepted: 23 September 2020 # Royal Academy of Medicine in Ireland 2020
Abstract Introduction Biclonal lymphoid disorders, when two distinct lymphoproliferative disorders (LPD) co-exist, are rare (incidence of 1.4%) and associated with a poor prognosis. NOTCH1 mutations occur in 10% of CLL at diagnosis, associated with a short disease-free interval and increased risk of Richter’s transformation. We hypothesised that the incidence of NOTCH1 mutations in CLL with a second LPD may be increased, because the mutation occurs early in leukaemogenesis, permitting clonal divergence. Methods We identified 19 patients with biclonal LPD at diagnosis: 11 with CLL and a second LPD (group A) and 8 with a second distinct CLL (group B). NOTCH1 mutation analysis was performed and clinical outcome investigated. Results Ten of 19 (52%) were NOTCH1 mutated: 5 in group A (45%) and 5 in group B (62.5%) with a favourable clinical outcome observed among this cohort with 28.7 (range 1–99) months of follow-up. Conclusion In conclusion, we identified a significant (52%) incidence of NOTCH1 mutations in CLL in the context of biclonal LPD, associated with an indolent clinical course. Keywords Biclonal lymphoproliferative disorder . Chronic lymphocytic leukaemia . NOTCH1 mutation . Richter’s transformation
Introduction B cell chronic lymphocytic leukaemia (B-CLL) is the commonest leukaemia in the Western world, accounting for 90% of chronic leukaemias in Europe and the USA [1]. A third of patients never require treatment, whereas the remainder progress with lymphadenopathy, B symptoms or marrow
failure requiring CLL-directed therapy. CLL remains incurable with recurrent relapses characterised by increasing therapy resistance or high-grade Richter’s transformation to diffuse large B cell lymphoma (DLBCL), or more rarely Hodgkin lymphoma. Biclonal LPDs are rare with an incidence of 1.4– 4.8%, were first recognised in 1997 and are usually characterised by CLL with another B-LPD such as mantle cell
Elisabeth Vandenberghe and Fiona Quinn contributed equally as last authors * Helen Fogarty [email protected] 1
Department of Cancer Molecular Diagnostics, St. James’s Hospital, Dublin, Ireland
2
Department of Haematology, St James’s Hospital and Trinity College, Dublin, Ireland
3
Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, 123 St Stephen’s Green, Dublin 2, Ireland
4
Department of Pathology, St James’s Hospital, Dublin, Ireland
5
Department of Haematology, Galway Clinic, Galway, Ireland
6
Department of Haematology, Waterford University Hospital, Waterford, Irela
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