Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia

2015 ◽  
Vol 156 (15) ◽  
pp. 592-597
Author(s):  
László Szerafin ◽  
János Jakó ◽  
Ferenc Riskó
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Prognostic Value ◽  
Lymphocytic Leukaemia ◽  
Treatment Time ◽  
Monocyte Count ◽  
Time To Treatment ◽  
Causes Of Mortality ◽  
The Absolute ◽  
The Impact ◽  
Overal Survival

Introduction: The low peripheral absolute lymphocyte and high monocyte count have been reported to correlate with poor clinical outcome in various lymphomas and other cancers. However, a few data known about the prognostic value of absolute monocyte count in chronic lymphocytic leukaemia. Aim: The aim of the authors was to investigate the impact of absolute monocyte count measured at the time of diagnosis in patients with chronic lymphocytic leukaemia on the time to treatment and overal survival. Method: Between January 1, 2005 and December 31, 2012, 223 patients with newly-diagnosed chronic lymphocytic leukaemia were included. The rate of patients needing treatment, time to treatment, overal survival and causes of mortality based on Rai stages, CD38, ZAP-70 positivity and absolute monocyte count were analyzed. Results: Therapy was necessary in 21.1%, 57.4%, 88.9%, 88.9% and 100% of patients in Rai stage 0, I, II, III an IV, respectively; in 61.9% and 60.8% of patients exhibiting CD38 and ZAP-70 positivity, respectively; and in 76.9%, 21.2% and 66.2% of patients if the absolute monocyte count was <0.25 G/l, between 0.25–0.75 G/l and >0.75 G/l, respectively. The median time to treatment and the median overal survival were 19.5, 65, and 35.5 months; and 41.5, 65, and 49.5 months according to the three groups of monocyte counts. The relative risk of beginning the therapy was 1.62 (p<0.01) in patients with absolute monocyte count <0.25 G/l or >0.75 G/l, as compared to those with 0.25–0.75 G/l, and the risk of overal survival was 2.41 (p<0.01) in patients with absolute monocyte count lower than 0.25 G/l as compared to those with higher than 0.25 G/l. The relative risks remained significant in Rai 0 patients, too. The leading causes of mortality were infections (41.7%) and the chronic lymphocytic leukaemia (58.3%) in patients with low monocyte count, while tumours (25.9–35.3%) and other events (48.1 and11.8%) occurred in patients with medium or high monocyte counts. Conclusions: Patients with low and high monocyte counts had a shorter time to treatment compared to patients who belonged to the intermediate monocyte count group. The low absolute monocyte count was associated with increased mortality caused by infectious complications and chronic lymphocytic leukaemia. The absolute monocyte count may give additional prognostic information in Rai stage 0, too. Orv. Hetil., 2015, 156(15), 592–597.

The prognostic value of smudge cells (Gumprecht shadows) in chronic lymphocytic leukaemia

2012 ◽  
Vol 153 (44) ◽  
pp. 1732-1737 ◽  
Author(s):  
László Szerafin ◽  
János Jakó ◽  
Ferenc Riskó ◽  
Zsuzsanna Hevessy
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Prognostic Value ◽  
Blood Smear ◽  
Lymphocytic Leukaemia ◽  
Annexin V ◽  
Inverse Correlation ◽  
Treated Group ◽  
Time To Treatment ◽  
Cell Percentage

Introduction: Smudge cells (Gumprecht shadows) are chronic lymphocytic leukaemic cells ruptured during peripherial blood smear preparation. It has been demonstrated to be linked to reduced expression of the cytoskeletal protein vimentin and its inverse correlation with the clinical outcome of the disease. Aims: Investigation of the percentage of smudge cells, CD38-, ZAP-70-positive cells and the time to treatment in patients with chronic lymphocytic leukaemia. Methods: Authors investigated the percentage of smudge cells, CD38- and ZAP-70-positive cells in the peripheral blood of 50 patients with chronic lymphocytic leukaemia and their correlation with the time to treatment. Results: 21 patients required treatment in the follow-up period. Their median smudge cell percentage was 9.9%, while it was 26.8% in the non-treated group. The cut-off value of smudge cell positivity was set to 20%. 59.3% of the patients with less than cut-off had to be treated in the follow-up time compared to 21.7% of patients with more smudge cells. These findings were similar to the prognostic value of CD38 and ZAP-70. The necessity of treatment increased to 75–77.8% with the combination of investigated markers. The time to treatment was 19 months when smudge cells were less than 20%, but above 20% it was 36.15 months. In case of low smudge cell percentage and CD38 positivity the time to treatment was 14.14 months and in case of high smudge cell percentage and CD38 negativity it was 32.92 months. In discordant cases the time to treatment was 18.43 months. The authors also present a case report that demonstrates the relationship between the percentage of smudge cells and apoptotic cells with annexin V and 7-AAD staining. Conclusions: Estimation of smudge cells on a blood smear could be a simple and cheap prognostic test in chronic lymphocytic leukaemia with sensitivity similar to CD38 and ZAP-70 estimation. Combination of these tests raised the sensitivity of their prognostic value. Orv. Hetil., 2012, 153, 1732–1737.

scholarly journals Quantification improves the prognostic value of CD38 expression in B-cell chronic lymphocytic leukaemia

2002 ◽  
Vol 118 (3) ◽  
pp. 755-761 ◽  
Author(s):  
Tryfonia Mainou-Fowler ◽  
Helen Dignum ◽  
Penelope R. A. Taylor ◽  
Anne M. Dickinson ◽  
Peter W. G. Saunders ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Prognostic Value ◽  
Lymphocytic Leukaemia ◽  
Cd38 Expression ◽  
Cell Chronic Lymphocytic Leukaemia

scholarly journals Expression of the transcribed ultraconserved region 70 and the related long non-coding RNA AC092652.2-202 has prognostic value in Chronic Lymphocytic Leukaemia

2018 ◽  
Vol 184 (6) ◽  
pp. 1045-1050 ◽  
Author(s):  
Riccardo Bomben ◽  
Alejandro Roisman ◽  
Tiziana D'Agaro ◽  
Giancarlo Castellano ◽  
Tycho Baumann ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Prognostic Value ◽  
Lymphocytic Leukaemia ◽  
Non Coding Rna ◽  
Long Non Coding Rna

B-cell chronic lymphocytic leukaemia: Prognostic value of the immunophenotype and the clinico-haematological features

1989 ◽  
Vol 31 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Alberto Orfao ◽  
Marcos Gonzalez ◽  
J. San Fernando Miguel ◽  
Agustin Rios ◽  
M. Consuelo Canizo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Prognostic Value ◽  
Lymphocytic Leukaemia ◽  
Cell Chronic Lymphocytic Leukaemia

scholarly journals Medical Comorbidities Assessed By CIRS Negatively Impact Survival in the Era of Targeted Therapies in CLL: A Multicenter Retrospective Analysis

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 918-918
Author(s):  
Max J Gordon ◽  
Stephen M Amrock ◽  
Xavier Issac Rivera ◽  
Spencer James ◽  
Sudhir Manda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Retrospective Analysis ◽  
Organ Dysfunction ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
The Impact

Abstract Introduction: The majority of patients with chronic lymphocytic leukemia (CLL) present with comorbidities, commensurate with the median age at diagnosis of 71 years. The Cumulative Illness Rating Scale (CIRS) is a widely used index which has been incorporated into clinical research in CLL. CIRS consists of 14 categories related to different body systems and scores the severity of each condition from 0-4. We have previously reported in a single-center study that CIRS predicted outcomes in patients with CLL treated with chemo-immunotherapy (CIT). However, to date it is not yet known how comorbidities impact outcomes in the era of novel agents. We tested a hypothesis that CIRS and severe organ dysfunction would retain prognostic significance. Methods: We conducted a retrospective analysis of patients with CLL who underwent treatment at three academic medical centers between 2000 and 2016. CIRS score was calculated as in Salvi et al, 2008. Overall survival (OS) and progression-free survival (PFS) were assessed by Cox proportional hazards models adjusting for performance status (PS), age group, and chemotherapy regimen. Survival analysis in patients treated with ibrutinib was adjusted for age, PS, Rai stage, del17p and prior treatment. In addition, the impact of severe organ dysfunction (CIRS-3+, i.e. CIRS score ≥3 in single organ system) was assessed. Results: Median age in patients receiving CIT was 65 years (N=233). The most common comorbidities were hypertension, endocrine (e.g. diabetes mellitus) and vascular (e.g. deep vein thrombosis). Fludarabine-Rituximab (N=61), Fludarabine-Cyclophosphamide-Rituximab (N=67), Rituximab-Cyclophosphamide-Vincristine-Prednisone (N=35), Bendamustine-Rituximab (N=38) and chlorambucil (N=47) were the most commonly used regimens. 79.5% of treatments were administered in a frontline setting. Average total CIRS was 6.6 and 47% had CIRS-3+. Median OS among all patients receiving CIT was 112 months (95% CI: 105 - 128 months). CIRS≥7 and CIRS3+ were associated with inferior OS compared to patients without significant comorbidities (87, 92 and 129 months, respectively, p&lt;0.05). In multivariate analysis, OS and PFS both decreased with each increase in total CIRS by one point (HR=1.09; p=0.006 and HR=1.05; p = 0.02), while CIRS-3+ was associated with inferior OS among patients treated with CIT (HR=1.50, p=0.01). In patients treated with ibrutinib the median age was 71 years (N=83), which was significantly older than in the CIT cohort (p&lt;0.001). The most common comorbidities were musculoskeletal (e.g., osteoarthritis), and gastrointestinal (e.g., acid reflux). Median follow up was 12 months (range, 1-39 months). Contrary to patients receiving CIT, 86% of patients had relapsed/refractory disease, with a median of 2 prior treatments (range 0-6). 35% had received prior fludarabine and 54% had received an alkylating agent. Average CIRS was 8.6 and 67% had CIRS-3+. Patients treated with ibrutinib who required dose reductions had higher CIRS (mean score 11.6 vs 7.6; p&lt;0.0003). CIRS-3+ was also associated with dose reduction (RR=4.6, p=0.01). In multivariable analysis, time to treatment failure, defined as ibrutinib discontinuation due to either disease progression or intolerable side effects, shortened with each increase in total CIRS score by one point (HR=1.23; p&lt;0.001). CIRS-3+ was similarly associated with increased risk of treatment failure in multivariable analysis (HR=3.80; p=0.02). In univariate analysis comparing low vs high CIRS (CIRS &lt;7 vs CIRS≥7), median time to treatment failure was 37 vs 23 months (p=0.01; Fig. 1A). OS at 24 months was 100% vs 79% (p=0.02; Fig 1B). Conclusion: In this multicenter retrospective analysis we show that CIRS has prognostic significance in patients with CLL treated with either CIT or ibrutinib, where increased comorbidities correlate with shortened progression-free and overall survival. CIRS appears to carry prognostic value in both upfront and relapsed settings, including patients whose disease can be salvaged with ibrutinib. Larger prospective studies of patients with lymphoid malignancies who have comorbidities are necessary to better define the prognostic value of CIRS in the era of targeted agents and determine the optimal approach to therapy of such patients. Figure 1 Figure 1. Disclosures Persky: Genentech: Consultancy; MorphoSys: Other: Independent Data Monitoring Committee member ; Verastem: Consultancy; Spectrum Pharmaceuticals: Research Funding.

scholarly journals The role of B-Cell Lymphoma-3 (BCL-3) in enabling the hallmarks of cancer: implications for the treatment of colorectal carcinogenesis

2020 ◽  
Vol 41 (3) ◽  
pp. 249-256 ◽  
Author(s):  
Danny N Legge ◽  
Adam C Chambers ◽  
Christopher T Parker ◽  
Penny Timms ◽  
Tracey J Collard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Lymphocytic Leukaemia ◽  
Tumour Response ◽  
B Cell Lymphoma ◽  
Hallmarks Of Cancer ◽  
Wide Range ◽  
The Impact

Abstract With its identification as a proto-oncogene in chronic lymphocytic leukaemia and central role in regulating NF-κB signalling, it is perhaps not surprising that there have been an increasing number of studies in recent years investigating the role of BCL-3 (B-Cell Chronic Lymphocytic Leukaemia/Lymphoma-3) in a wide range of human cancers. Importantly, this work has begun to shed light on our mechanistic understanding of the function of BCL-3 in tumour promotion and progression. Here, we summarize the current understanding of BCL-3 function in relation to the characteristics or traits associated with tumourigenesis, termed ‘Hallmarks of Cancer’. With the focus on colorectal cancer, a major cause of cancer related mortality in the UK, we describe the evidence that potentially explains why increased BCL-3 expression is associated with poor prognosis in colorectal cancer. As well as promoting tumour cell proliferation, survival, invasion and metastasis, a key emerging function of this proto-oncogene is the regulation of the tumour response to inflammation. We suggest that BCL-3 represents an exciting new route for targeting the Hallmarks of Cancer; in particular by limiting the impact of the enabling hallmarks of tumour promoting inflammation and cell plasticity. As BCL-3 has been reported to promote the stem-like potential of cancer cells, we suggest that targeting BCL-3 could increase the tumour response to conventional treatment, reduce the chance of relapse and hence improve the prognosis for cancer patients.

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