In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristics

Rigolin, Gian Matteo; Saccenti, Elena; Guardalben, Emanuele; Cavallari, Maurizio; Formigaro, Luca; Zagatti, Barbara; Visentin, Andrea; Mauro, Francesca Romana; Lista, Enrico; Bassi, Cristian; Lupini, Laura; Quaglia, Francesca Maria; Urso, Antonio; Bardi, Maria Antonella; Bonaldi, Laura; Volta, Eleonora; Tammiso, Elisa; Ilari, Caterina; Cafforio, Luciana; Melandri, Aurora; Cavazzini, Francesco; Negrini, Massimo; Semenzato, Gianpietro; Trentin, Livio; Cuneo, Antonio

doi:10.1111/bjh.15174

Cited by 37 publications

(35 citation statements)

References 15 publications

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“…None of the patients with a complex karyotype (≥ 3) as well as del(11q) and del(17p) attained a CR after chemotherapy. In CLL, the prognostic significance of a complex karyotype had also been reported in other recent studies [23][24][25].…”

Section: Discussionsupporting

confidence: 68%

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Choi

Lee

Jung

et al. 2021

Korean J Intern Med

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Background/Aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 10 3 /μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). Conclusions: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

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Section: Discussionsupporting

confidence: 68%

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Choi

Lee

Jung

et al. 2021

Korean J Intern Med

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“…Similar to other haematological malignancies, the earliest prognostic abnormalities detected were cytogenetic: del(17p)/del(11q) and del(13q) were associated with shorter and longer OS rates respectively [121]. More recently, a complex karyotype (defined as ≥ 3 cytogenetic abnormalities in a single clone) has been shown to be associated with a poor prognosis with those patients with unbalanced chromosomal rearrangements having the worst prognosis [122]. However, technical difficulties with the culture of CLL cells means failure rates for conventional karyotyping are high and alternative technologies such as WGS may be required.…”

Section: Chronic Lymphocytic Leukaemiamentioning

confidence: 78%

Application of Genomics to Clinical Practice in Haematological Malignancy

et al. 2019

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Purpose of Review The usual abundance of fresh cells and high-quality DNA derived from bone marrow aspirate and peripheral blood mean haematological malignancies are at the forefront of the application of genomics to malignancy. This review evaluates where genomics is routinely used in clinical care and where opportunities for further application exist. Recent Findings The 2016 revision of the WHO classification of tumours of haematopoietic and lymphoid tissues increased the number of disease entities defined by, or whose diagnosis was strongly supported by, a specific genetic change. Increasingly combinations of mutations rather than individual lesions are being used to genomically classify heterogeneous disorders to inform prognosis and direct treatment. Furthermore, the role of different genetic aberrations as markers of measurable residual disease is being evaluated in clinical trials to allow intensification/de-intensification of treatment as appropriate and early detection of relapse. Summary Implementation of broader sequencing technologies such as whole exome/genome sequencing coupled with continuing developments in genomic technology to improve turnaround times are likely to further reinforce the centrality of genomics in the management of haematological malignancies.

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“…Recently, Rigolin et al , showed that within patients carrying CK as defined by the presence of 3 or more aberrations, the presence of unbalanced translocations (i.e. chromosome additions, derivatives, insertions, duplications, ring-, dicentric- and marker-chromosomes) was associated with a worse outcome in terms of OS and TTFT (HR 2.773; 95% CI, 1.056-7.281; P=0.038 and HR 2.375; 95% CI, 1.027-5.492; P=0.043) [ 97 ]. Interestingly, a distinct mRNA expression profile, with a deregulation of genes involved in cell cycle control and DNA damage response, was documented in patients with a CK carrying unbalanced rearrangements [ 97 ].…”

Section: Resultsmentioning

confidence: 99%

Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia

et al. 2018

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The complex karyotype (CK) is an established negative prognostic marker in a number of haematological malignancies. After the introduction of effective mitogens, a growing body of evidence has suggested that the presence of 3 or more aberrations by conventional banding analysis (CBA) is associated with an unfavorable outcome in chronic lymphocytic leukemia (CLL). Thus, the importance of CBA was recognized by the 2018 guidelines of the International Workshop on CLL, which proposed the introduction of CBA in clinical trials to validate the value of karyotype aberrations.Indeed, a number of observational studies showed that cytogenetic aberrations and, particularly, the CK may have a negative independent impact on objective outcome measures (i.e. time to first treatment, progression free survival, time to chemorefractoriness and overall survival) both in patients treated with chemoimmunotherapy and, possibly, in patients receiving novel mechanism-based treatment.Here, we set out to present the scientific evidence supporting the significance of CK as a prognostic marker in CLL and to discuss the biological basis showing that the CK is a consequence of genomic instability.

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In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristics

Cited by 37 publications

References 15 publications

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Application of Genomics to Clinical Practice in Haematological Malignancy

Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia

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