Chronic lymphocytic leukemia in the elderly: clinico-biological features, outcomes, and proposal of a prognostic model

Baumann, Tycho; Delgado, Julio; Santacruz, Rodrigo; Martínez‐Trillos, Alejandra; Royo, Cristina; Navarro, Alba; Pinyol, Magda; Rozman, Marı́a; Pereira, Arturo; Villamor, Neus; Aymerich, Marta; López, Cristina; Carrió, Ana; Montserrat, Emili

doi:10.3324/haematol.2014.107326

Cited by 65 publications

(57 citation statements)

References 37 publications

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“…Indeed, relevant comorbidities may shorten life expectancy and may reduce treatment tolerance, 3,17 and modern treatment algorithms recommended evaluating not only age, clinical staging, and disease-specific prognostic biomarkers, but also comorbidities to guide clinical decisions, 13,18 particularly in the era of novel drugs. 19 However, the prognostic impact of comorbidities and of the CK in the era of mechanism-based treatment needs to be specifically addressed in larger series of patients treated for longer periods of time because in our cohort of CLL, these agents were offered only in more recent years.…”

mentioning

confidence: 99%

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

Rigolin

Cavallari

Quaglia

et al. 2017

Blood

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mentioning

confidence: 99%

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

Rigolin

Cavallari

Quaglia

et al. 2017

Blood

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“…In one study, the poor outcome of patients with comorbidities was due to a combined increase of treatment-related, CLL-unrelated and CLL-related mortality, thus suggesting complex interactions between the haematological disease, its treatment and comorbidities [11]. In another study, the outcome of patients with comorbidities was poor because of a sole increase in CLLunrelated mortality but not in CLL-related mortality [17].…”

Section: Impact Of Comorbidity On Outcomes In Patients With Cllmentioning

confidence: 96%

“…Commonly detected comorbidities in this study were hypertension (55 %), hyperlipidaemia (37 %), coronary artery disease (24 %), atrial fibrillation (21 %), diabetes mellitus (22 %) and osteoarthritis (22 %). In a cohort of 949 patients diagnosed with CLL in a haematology department of a university hospital, the median total CIRS score at the time of diagnosis was 5 [17]. A single-centre study of 133 untreated subjects found that 53 % of the patients had a total CIRS score of 6 or higher [18], while in a single-centre study of 143 untreated patients, fewer than 20 % had a total CIRS score above 6 [19].…”

Section: Prevalence Of Comorbidity In Patients With Cllmentioning

confidence: 99%

Pharmacotherapeutic Management of Chronic Lymphocytic Leukaemia in Patients with Comorbidities: New Agents, New Hope

Goede

Hallek

2015

Drugs Aging

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Chronic lymphocytic leukaemia (CLL) is mostly considered a disease of the elderly. As such, many patients present with comorbidities. Several scores allow for a qualitative and quantitative assessment of comorbidity in patients with CLL. Although our knowledge about the impact of comorbidity on outcomes in patients with CLL is still incomplete, it is becoming increasingly apparent that comorbidities could negatively interfere with CLL treatment. Recently, a number of new agents have been approved for use in patients with previously untreated CLL and comorbidities (i.e. obinutuzumab, ofatumumab), as well as in patients with previously treated or high-risk CLL (i.e. idelalisib, ibrutinib). This review discusses the role of comorbidity in patients with CLL, together with the changing treatment landscape for CLL in this patient population.

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“…Clinical trials evaluating immediate chemo(immuno)therapy in early stage CLL so far failed to show an overall survival (OS) benefit; thus, watch and wait has remained the standard of care. 4,5 However, today novel treatment approaches are available (see below), and a wealth of prognostic factors have been identified, including lymphocyte doubling time (LDT), bone marrow infiltration pattern, serum thymidine kinase (TK) and ␤2-microglobulin (␤2-MG) levels, genomic aberrations assessed by fluorescence in situ hybridization (FISH), ZAP70, CD38, and CD49d expression, as well as the mutational status and structure of the immunoglobulin heavy-chain variable genes (IGHV) and gene mutations, most prominently TP53 (for overviews, see Stilgenbauer and Zenz 6 and Baumann et al 7 ). Numerous single markers and various models, scores, or nomograms have been reported to be associated with prognosis in early stage CLL, but there is a lack of prospective validation within clinical trials ( [8][9][10][11][12][13][14] ).…”

Section: Standard Approach To Early Stage Asymptomatic Patientsmentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] 72 This system clearly holds great promise to refine risk stratification based on staging and single parameters alone. However, it is derived from trials based on chemo(immuno)-therapy and may be challenged by the advent of the novel agents that may in themselves require the development of integrated risk scores highlighting the "moving target" nature of the prognostic/ predictive factor topic.…”

Section: Mrd Evaluationmentioning

confidence: 99%

Prognostic markers and standard management of chronic lymphocytic leukemia

Stilgenbauer

2015

Hematology

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Chronic lymphocytic leukemia (CLL) is usually diagnosed in early stage, asymptomatic patients, and, although a wealth of prognostic parameters have been identified, the standard approach is a "watch and wait" strategy irrespective of risk factors. Therapy is only indicated if "active disease" criteria (International Workshop on Chronic Lymphocytic Leukemia guidelines) are met, and the routine upfront treatment is a combination of CD20 antibody (rituximab, ofatumumab or obinutuzumab) and chemotherapy (fludarabine /cyclophosphamide, bendamustine, chlorambucil), with the choice mainly determined by physical fitness of the patient. The major subgroup in which this approach does not result into satisfactory efficacy is in CLL with 17p deletion (17pϪ) or TP53 mutation (TP53mut). Likewise, patients with a short initial response duration (i.e., Ͻ24-26 months) have a dismal outcome with chemoimmunotherapy salvage. Therefore, these patients have been referred to as "ultra high risk," and, in these subgroups, novel agents such as signaling kinase inhibitors (also termed B-cell receptor signaling inhibitors; e.g., ibrutinib targeting Bruton tryosine kinase, idelalisib targeting phosphoinositide 3-kinase) and BCL2 antagonists (venetoclax, formerly ABT-199/GDC-0199) have shown dramatic efficacy. Ibrutinib and idelalisib are currently approved for the treatment of relapsed or refractory CLL or frontline treatment of 17pϪ/TP53mut CLL regardless of fitness. Therefore, these agents are challenging the concept of adjusting treatment to fitness and TP53 status, because they offer remarkable efficacy combined with exceptional tolerability. Nevertheless, it appears that 17pϪ/TP53mut retains an adverse prognostic impact, making additional improvement a primary research goal aimed at the development of the best combinations and/or sequences of these new agents, as well as prognostic and predictive markers guiding their use. Learning Objectives• "Watch and wait" is the standard of care for early stage, asymptomatic chronic lymphocytic leukemia (CLL) patients irrespective of prognostic factors, but these may inform counseling and follow-up • 17pϪ/TP53mut, physical fitness (age), and duration of previous response are the most critical determinants of treatment choice • Combination of CD20 antibody and chemotherapy, with the choice determined by fitness, is the standard upfront treatment for CLL patients without 17pϪ/TP53mut • Based on dramatic efficacy and favorable toxicity profile of novel agents such as ibrutinib, idelalisib, and venetoclax, these agents are the preferred treatment approach for "ultra high-risk" CLL (17pϪ/TP53mut and refractory/early relapse) patients • The role of allogenic stem cell transplantation needs reassessment, and individualized counseling is required for young "ultra high-risk" patients • There is a strong need for additional research on improved treatment and prognostic, as well as predictive markers in the era of novel "biological" approaches, aimed at finite treatment duration and eventually a cure

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Chronic lymphocytic leukemia in the elderly: clinico-biological features, outcomes, and proposal of a prognostic model

Cited by 65 publications

References 37 publications

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

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

Pharmacotherapeutic Management of Chronic Lymphocytic Leukaemia in Patients with Comorbidities: New Agents, New Hope

Prognostic markers and standard management of chronic lymphocytic leukemia

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