Prognostic Value of Complex Karyotype and del(17p) in Patients with Chronic Lymphocytic Leukemia
DOI:
https://doi.org/10.5281/zenodo.22238182Keywords:
Chronic Lymphocytic Leukaemia, Complex Karyotype, del(17p), TP53, PrognosticationAbstract
Complex karyotype has been treated as a single adverse category in chronic lymphocytic leukaemia for two decades. The largest analysis of the question found it is nothing of the kind: five or more abnormalities are adverse regardless of anything else, three or four matter only alongside a TP53 lesion, and one particular complex pattern is associated with better survival than a normal karyotype. Objectives: To review the published evidence on complex karyotype and del(17p) in chronic lymphocytic leukaemia: how each is defined and detected, how often they occur and co-occur, what each predicts under chemoimmunotherapy and under targeted therapy, and whether karyotypic complexity carries information independent of TP53 status. Material and Methods: Narrative review of cytogenetic cohort analyses, trial correlative studies, sequencing work, consensus guidelines and methodological comparisons indexed in PubMed and the major haematology journals. Studies were eligible if they reported the frequency or prognostic effect of karyotypic
complexity or TP53 aberration in a defined chronic lymphocytic leukaemia population. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: Deletion of 17p occurs in 4 to 10 per cent of patients at diagnosis and in up to 40 per cent at relapse after chemoimmunotherapy, with the remaining TP53 allele mutated in around 80 to 90 per cent of deleted cases. In a series of 3,539 patients, five or more chromosomal abnormalities defined a high-complexity group comprising 233 patients (6.5 per cent) with the shortest overall survival, independent of immunoglobulin mutational status and TP53 status. Three or four abnormalities were clinically relevant only in the presence of a TP53 lesion. Complex karyotypes characterised by trisomy 12 with trisomy 19 were associated with longer survival than in patients without a complex karyotype. Complexity retained prognostic value in patients treated with ibrutinib and with venetoclax, and in one series was associated with median progression-free survival of 34 against 40 months. Conclusion: Counting abnormalities is not the same as measuring risk. A threshold of three, still widely used, groups together patients whose outcomes differ in both directions, and the composition of the karyotype matters as much as the count. Abbreviations: CLL – Chronic Lymphocytic Leukaemia, CK – Complex Karyotype, hCK – High Complex Karyotype, CBA – Chromosome Banding Analysis, FISH – Fluorescence In Situ Hybridisation, IGHV – Immunoglobulin Heavy Chain Variable Region, M-CLL – IGHV-Mutated CLL, U-CLL – IGHV-Unmutated CLL, CIT – Chemoimmunotherapy, TTFT – Time to First Treatment, OS – Overall Survival, PFS – Progression-Free Survival, CLL-IPI – CLL International Prognostic Index.
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