Scientific Letters
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases
https://doi.org/10.4084/MJHID.2026.070

A case of Pseudo-Richter Transformation following zanubrutinib discontinuation in CLL

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Published: September 1, 2026
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Chronic Lymphocytic Leukaemia, Pseudo-Richter, BTK inhibitors, Zanubrutinib

Authors

Luca Laurenti
1. UOSD Leucemia Linfatica Cronica, Dipartimento di scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy 2. Università Cattolica del Sacro Cuore, Istituto di Ematologia, Roma, Italy, Italy.
Tommaso Quaranta
tommasoquarantamd@gmail.com
Università Cattolica del Sacro Cuore, Istituto di Ematologia, Roma, Italy, Italy.
Annamaria Tomasso
UOSD Leucemia Linfatica Cronica, Dipartimento di scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Italy.
Luca Stirparo
UOSD Leucemia Linfatica Cronica, Dipartimento di scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Italy.
Pier Luigi Abbate
Università Cattolica del Sacro Cuore, Istituto di Ematologia, Roma, Italy, Italy.
Arianna Bakacs
Università Cattolica del Sacro Cuore, Fondazione Policlinico Gemelli Roma, Istituto di Patologia, Roma, Italy, Italy.
Natalia Cappoli
Università Cattolica del Sacro Cuore, Fondazione Policlinico Gemelli Roma, Istituto di Patologia, Roma, Italy, Italy.
Arianna Di Napoli
Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Roma, Italy., Italy.
Dimitar Efremov
Department of Medical Sciences, Macedonian Academy of Sciences and Arts, Skopje, North Macedonia, North Macedonia.
Flaminia Bellisario
Fondazione Policlinico Universitario A. Gemelli IRCCS, UOSD Malattie Linfoproliferative Extramidollari, Dipartimento di scienze di laboratorio ed ematologiche, Roma, Italy, Italy.
Valter Gattei
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy, Italy.
Carmelo Caldarella
Unit of Nuclear Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy., Italy.
Maria Luisa Calcagni
Unit of Nuclear Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy., Italy.
Francesco Autore
UOSD Leucemia Linfatica Cronica, Dipartimento di scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Italy.
Idanna Innocenti
UOSD Leucemia Linfatica Cronica, Dipartimento di scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Italy.

Temporary discontinuation of covalent Bruton tyrosine kinase inhibitors (cBTKi) can trigger a "disease flare" that mimics Richter transformation (RT). This phenomenon, known as pseudo-Richter (pseudo-RT), is a transient, reversible proliferation of large, atypical B cells. We report the first known case of pseudo-RT following zanubrutinib interruption due to hepatotoxicity in a 75-year-old man with NOTCH1-mutated chronic lymphocytic leukemia (CLL). 

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Ethics Approval

Chronic Lymphocytic Leukemia, Richter, B-Cell Lymphoproliferative disorders (B-LPDs)

Supporting Agencies

All authors declare no conflict of interest. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

How to Cite



“A case of Pseudo-Richter Transformation following zanubrutinib discontinuation in CLL” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1), p. e2026070. doi:10.4084/MJHID.2026.070.
Copyright (c) 2026 Luca Laurenti, Tommaso Quaranta, Annamaria Tomasso, Luca Stirparo, Pier Luigi Abbate, Arianna Bakacs, Natalia Cappoli, Arianna Di Napoli, Dimitar Efremov, Flaminia Bellisario, Valter Gattei, Carmelo Caldarella, Maria Luisa Calcagni, Francesco Autore, Idanna Innocenti Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.