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

Voso, Maria Teresa; Pandzic, Tatjana; Falconi, Giulia; Denčić‐Fekete, Marija; Bellis, Eleonora De; Scarfò, Lydia; Ljungström, Viktor; Iskas, Michail; Poeta, Giovanni Del; Ranghetti, Pamela; Laidou, Stamatia; Cristiano, Antonio; Plevová, Karla; Imbergamo, Silvia; Engvall, Marie; Zucchetto, Antonella; Salvetti, Chiara; Mauro, Francesca Romana; Stavroyianni, Niki; Cavelier, Lucia; Ghia, Paolo; Σταματόπουλος, Κώστας; Fabiani, Emiliano; Baliakas, Panagiotis

doi:10.1111/bjh.18129

Cited by 13 publications

(5 citation statements)

References 35 publications

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“…Furthermore, FCR should be particularly avoided in patients with clonal hematopoiesis of indeterminate potential (CHIP), as they have an even higher risk of developing myeloid malignancies. 42 In the current era, patients without adverse prognostic features could experience an excellent prognosis also with novel agents without the risk of a treatment-related myeloid malignancy. 41 , 43 Our findings indicate that we could reduce the incidence of treatment-related myeloid malignancies by simply omitting FCR from CLL treatment options.…”

Section: Discussionmentioning

confidence: 99%

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Chatzikonstantinou,

Scarfò,

Karakatsoulis

et al. 2023

eClinicalMedicine

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Section: Discussionmentioning

confidence: 99%

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Chatzikonstantinou,

Scarfò,

Karakatsoulis

et al. 2023

eClinicalMedicine

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“…In one study, 30 pathogenic or likely pathogenic variants were identified in 77% of patients who later developed t-MN, compared to 12% of patients in the control group who received the same treatment. Remarkably, upon retrospective analysis, the same variants were identified in 62.5% of patients at the time of CLL diagnosis, suggesting their pre-existing and clonal nature [45].…”

Section: The Role Of Clonal Hematopoiesismentioning

confidence: 84%

Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression

Travaglini,

Marinoni,

Visconte

et al. 2024

Biomedicines

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Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature and the subsets of these conditions have changed frequently over time, and despite the fact that, in the last classification, they lost their autonomous entity status and became disease qualifiers, the recognition of this feature remains of major importance. Furthermore, in recent years, extensive studies focusing on clonal hematopoiesis and germline variants shed light on the mechanisms of positive pressure underpinning the rise of driver gene mutations in t-MN. In this manuscript, we aim to review the evolution of defining criteria and characteristics of t-MN from a clinical and biological perspective, the advances in mechanistic aspects of malignant progression and the challenges in prevention and management.

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“…However, it is essential to keep in mind that also putative tumor-free material (i.e. saliva or CD19 negative blood cells) can be contaminated by CLL cells [ 103 ], active myeloid malignancy precursors (e.g., therapy-related myelodysplastic syndrome [ 104 ] or myeloproliferative neoplasm) or clonal hematopoiesis of indeterminate potential. Allelic frequency of >30% (SNVs) or >20% (small insertions/deletions) in non-tumor tissue is expected for variants of germline origin [ 100 ], and lower VAFs are indicative of cancer cell contamination or, rarely, mosaicism.…”

Section: Interpretation Of the Results And Reportingmentioning

confidence: 99%

ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—2024 update

Malcikova,

Pavlova,

Baliakas

et al. 2024

Leukemia

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In chronic lymphocytic leukemia (CLL), analysis of TP53 aberrations (deletion and/or mutation) is a crucial part of treatment decision-making algorithms. Technological and treatment advances have resulted in the need for an update of the last recommendations for TP53 analysis in CLL, published by ERIC, the European Research Initiative on CLL, in 2018. Based on the current knowledge of the relevance of low-burden TP53-mutated clones, a specific variant allele frequency (VAF) cut-off for reporting TP53 mutations is no longer recommended, but instead, the need for thorough method validation by the reporting laboratory is emphasized. The result of TP53 analyses should always be interpreted within the context of available laboratory and clinical information, treatment indication, and therapeutic options. Methodological aspects of introducing next-generation sequencing (NGS) in routine practice are discussed with a focus on reliable detection of low-burden clones. Furthermore, potential interpretation challenges are presented, and a simplified algorithm for the classification of TP53 variants in CLL is provided, representing a consensus based on previously published guidelines. Finally, the reporting requirements are highlighted, including a template for clinical reports of TP53 aberrations. These recommendations are intended to assist diagnosticians in the correct assessment of TP53 mutation status, but also physicians in the appropriate understanding of the lab reports, thus decreasing the risk of misinterpretation and incorrect management of patients in routine practice whilst also leading to improved stratification of patients with CLL in clinical trials.

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

Cited by 13 publications

References 35 publications

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression

ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia—2024 update

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