In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI

Rigolin, Gian Matteo; Cavallari, Maurizio; Quaglia, Francesca Maria; Formigaro, Luca; Lista, Enrico; Urso, Antonio; Guardalben, Emanuele; Liberatore, Carmine; Faraci, Danilo Giuseppe; Saccenti, Elena; Bassi, Cristian; Lupini, Laura; Bardi, Maria Antonella; Volta, Eleonora; Tammiso, Elisa; Melandri, Aurora; Negrini, Massimo; Cavazzini, Francesco; Cuneo, Antonio

doi:10.1182/blood-2017-03-772285

Cited by 79 publications

(61 citation statements)

References 21 publications

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“…Because the distribution of chromosomal abnormalities, a primary predictor of disease behavior, appears to be similar across different patient age groups, comorbidities are thought to significantly contribute to the poor outcomes of patients with CLL. Indeed, the impact of comorbidities on overall survival (OS) was similar to the negative impact of a complex karyotype in a series of 335 patients with CLL who were treated with chemoimmunotherapy (CIT) …”

Section: Introductionmentioning

confidence: 93%

Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib

Gordon

Churnetski

Alqahtani

et al. 2018

Cancer

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Section: Introductionmentioning

confidence: 93%

Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib

Gordon

Churnetski

Alqahtani

et al. 2018

Cancer

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“…In addition to the well-established recurrent cytogenetic aberrations with prognostic significance in CLL [100], complex karyotype (CK), defined by the presence of at least 3 numerical and/or structural abnormalities [101] is detectable in 14-35% of cases [102][103][104][105] and imparts further prognostic and potential predictive information both in the setting of CIT [49,103] and targeted therapy [60,106].…”

Section: Complex Karyotypementioning

confidence: 99%

An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

Cohen

Bomben

Pozzo

et al. 2020

Cancers

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Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. Novel biomarkers discovered over the past 20 years have revolutionized the way clinicians approach prognostication and treatment especially in the chemotherapy-free era. Herein, we review the best established prognostic and predictive biomarkers in the setting of chemoimmunotherapy (CIT) and novel targeted therapy. We propose that TP53 disruption (defined as either TP53 mutation or chromosome 17p deletion), unmutated immunoglobulin heavy chain variable region gene status (UM IGHV), NOTCH1 mutation, and CD49d expression are the strongest prognosticators of disease progression and overall survival in the field of novel biomarkers including recurrent gene mutations. We also highlight the predictive role of TP53 disruption, UM IGHV, and NOTCH1 mutation in the setting of CIT and TP53 disruption and CD49d expression in the setting of novel targeted therapy employing B-cell receptor (BCR) and B-cell lymphoma-2 (BCL2) inhibition. Finally, we discuss future directions in the field of biomarker development to identify those with relapsed/refractory disease at risk for progression despite treatment with novel therapies.

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“…IGHV status, age, β2‐MG, and TP53 mutation were the prognostic factors included in CLL‐IPI, so our results support the conclusion that CLL‐IPI can distinguish patients with high risk from low risk in del(17p) group . Recently, CK was considered as one of the most important prognostic indicators associated with poor outcome, independently of CLL‐IPI . In the presence of del(17p), patients without CK had a significantly longer TTFT than those with CK.…”

Section: Discussionmentioning

confidence: 99%

“…21 Recently, CK was considered as one of the most important prognostic indicators associated with poor outcome, independently of CLL-IPI. 22 In the presence of del(17p), patients without CK had a significantly longer TTFT than those with CK. However, we observed no significant difference in OS between the two groups.…”

Section: Survival Analysis Based On Cytogenetic Clonesmentioning

confidence: 94%

The percentage of cells with 17p deletion and the size of 17p deletion subclones show prognostic significance in chronic lymphocytic leukemia

Yuan

Zhu

et al. 2018

Genes Chromosomes & Cancer

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TP53 disruption is considered to be the most important prognostic factor in chronic lymphocytic leukemia (CLL), but not all patients with TP53 disruption have similar dismal outcomes. We evaluated the prognostic value of TP53 disruption in CLL patients without treatment indications. Data of 305 CLL patients were analyzed. 41 of them (13%) had TP53 disruption. Patients with lower percentage of cells with del(17p) had significantly better survival. Patients with mutated IGHV, β2‐microglobulin ≤3.5 mg/L, wild‐type TP53, age ≤65 years or without complex karyotype (CK) had relatively favorable outcomes in the del(17p) group. Furthermore, patients with del(17p) as a minor clone showed survival advantage compared with those with del(17p) as a major clone. These data suggest that the percentage of cells with del(17p), the size of the del(17p) subclone, CLL International Prognostic Index, and CK should be considered to build refined prognostication models for patients with TP53 disruption.

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In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI

Abstract: In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IP

Cited by 79 publications

References 21 publications

Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib

Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib

An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy

The percentage of cells with 17p deletion and the size of 17p deletion subclones show prognostic significance in chronic lymphocytic leukemia

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