• Helen Fogarty, Anita Dowling, David O'Brien, Steve Langabeer, Christopher Laurence Bacon, Richard Flavin, Michael O'Dwyer, Brian Hennessy, Hilary O'Leary, Gerard Crotty, Robert Henderson, James Nolan, Patrick Thornton, Elisabeth Vandenberghe, and Fiona Quinn.
• Department of Cancer Molecular Diagnostics, St. James's Hospital, Dublin, Ireland. fogarthm@tcd.ie.
• Ir J Med Sci. 2021 Aug 1; 190 (3): 1087-1094.

IntroductionBiclonal 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.MethodsWe 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.ResultsTen 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.ConclusionIn conclusion, we identified a significant (52%) incidence of NOTCH1 mutations in CLL in the context of biclonal LPD, associated with an indolent clinical course.© 2020. Royal Academy of Medicine in Ireland.

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