Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy

Authors	VOSO Maria-Teresa PANDZIC Tatjana FALCONI Giulia DENCIC-FEKETE Marija ELEONORA De Bellis SCARFO Lydia LJUNGSTROM Viktor ISKAS Michail GIOVANNI Del Poeta RANGHETTI Pamela LAIDOU Stamatia CRISTIANO Antonio PLEVOVÁ Karla IMBERGAMO Silvia ENGVALL Marie ZUCCHETTO Antonella SALVETTI Chiara MAURO Francesca R STAVROYIANNI Niki CAVELIER Lucia GHIA Paolo STAMATOPOULOS Kostas FABIANI Emiliano BALIAKAS Panagiotis
Year of publication	2022
Type	Article in Periodical
Magazine / Source	British journal of haematology
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://onlinelibrary.wiley.com/doi/10.1111/bjh.18129
Doi	http://dx.doi.org/10.1111/bjh.18129
Keywords	CHIP and FCR; CLL; t-MN
Description	Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0-6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1-5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.