International Prognostic Score (IPS-A) for Patients with Early Stage Chronic Lymphocytic Leukemia

2019 ◽  
Vol 19 ◽  
pp. S278 ◽  
Author(s):  
Adalgisa Condoluci ◽  
Lodovico Terzi di Bergamo ◽  
Petra Langerbeins ◽  
Manuela Hoechstetter ◽  
Carmen Herling ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Prognostic Score ◽  
Lymphocytic Leukemia ◽  
International Prognostic Score

INTERNATIONAL PROGNOSTIC SCORE FOR EARLY STAGE CHRONIC LYMPHOCYTIC LEUKEMIA (IPS-A)

2019 ◽  
Vol 37 ◽  
pp. 81-82
Author(s):  
A. Condoluci ◽  
L. Terzi di Bergamo ◽  
P. Langerbeins ◽  
M. Hoechstetter ◽  
C. Herling ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Prognostic Score ◽  
Lymphocytic Leukemia ◽  
International Prognostic Score

scholarly journals International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia

Blood ◽  
2020 ◽  
Vol 135 (21) ◽  
pp. 1859-1869 ◽  
Author(s):  
Adalgisa Condoluci ◽  
Lodovico Terzi di Bergamo ◽  
Petra Langerbeins ◽  
Manuela A. Hoechstetter ◽  
Carmen D. Herling ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Risk Score ◽  
Early Stage ◽  
Prognostic Score ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Intermediate Risk ◽  
Early Stage Disease ◽  
International Prognostic Score

Abstract Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 × 109/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.

Frequency and clinical relevance of coding and noncoding NOTCH1 mutations in early stage Binet A chronic lymphocytic leukemia patients

2020 ◽  
Vol 38 (3) ◽  
pp. 406-408 ◽  
Author(s):  
Marta Lionetti ◽  
Marzia Barbieri ◽  
Vanessa Favasuli ◽  
Elisa Taiana ◽  
Sonia Fabris ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Relevance ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Notch1 Mutations

scholarly journals Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4259-4264 ◽  
Author(s):  
M Sarfati ◽  
S Chevret ◽  
C Chastang ◽  
G Biron ◽  
P Stryckmans ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Disease Progression ◽  
Early Stage ◽  
Lymphocytic Leukemia ◽  
Study Entry ◽  
Clinical Staging ◽  
Soluble Cd23

Abstract Prognosis of B-cell chronic lymphocytic leukemia (CLL) is based on clinical staging whose limitation is the failure to assess whether the disease will progress or remain stable in early stage (Binet A, or Rai 0, I, II) patients. We previously reported that soluble CD23 (sCD23), a protein derived from the B-cell membrane CD23 Ag, is selectively elevated in the serum of CLL patients. This prospective study assessed the predictive value of serum sCD23 level measured at study entry on the overall survival of all CLL patients and on disease progression of stage Binet A patients. Prognostic value of repeated measurements of sCD23 over time in stage A patients was also analyzed. One hundred fifty-three CLL patients were prospectively followed with a median follow-up of 78 months. Eight clinical or biological parameters were collected from the date of the first sCD23 measurement. At study entry, by Cox model, Binet staging (P = .0001) and serum sCD23 level (P = .03) appeared as prognostic factors for survival. Patients with sCD23 level above median value (> 574 U/mL) had a significantly worse prognosis than those with lower values (median survival of 53 v 100+ months, P = .0001). During follow-up, sCD23 doubling time increased by 3.2 the risk of death (P = .001). Among stage A patients (n = 100), sCD23 determination at study entry was the sole variable predictive of disease progression, patients with sCD23 level above 574 U/mL had a median time progression of 42 months versus 88 months for those with lower levels (P = .0001). Stage A patients who doubled their sCD23 level exhibited a 15-fold increased risk of progression (P = .0001) and, in addition, the sCD23 increase preceded by 48 months disease progression. We conclude that in CLL patients, serum sCD23 level provides significant additional prognostic information in terms of overall survival. Most interestingly, among early stage patients, sCD23 determination at diagnosis and during the course of the disease may help to the early identification of patients who will rapidly progress to upper stages.

Abdominal Computed Tomography Predicts Progression in Patients With Rai Stage 0 Chronic Lymphocytic Leukemia

2007 ◽  
Vol 25 (12) ◽  
pp. 1576-1580 ◽  
Author(s):  
Ana Muntañola ◽  
Francesc Bosch ◽  
Pedro Arguis ◽  
Eduardo Arellano-Rodrigo ◽  
Carmen Ayuso ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Strong Predictor ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Clinical Information ◽  
Lymphocytic Leukemia ◽  
Abdominal Ct ◽  
Work Up

Purpose Whether computed tomography (CT) should be routinely included in the diagnostic work-up in patients with chronic lymphocytic leukemia (CLL) has not yet been determined. The aim of this study was to analyze the prognostic significance of abdominal CT in patients with CLL in Rai clinical stage 0. Patients and Methods Abdominal CT was performed at diagnosis in 140 patients consecutively diagnosed with CLL in Rai stage 0 disease. Results An abnormal abdominal CT was found in 38 patients (27%). Abnormal CT correlated with increased bone marrow infiltration (P = .024), high lymphocyte count (P = .001), increased ZAP-70 expression (P = .003), and short lymphocyte doubling time (LDT; P = .007). Patients with abnormal CT progressed more frequently and had a shorter time to progression than those with normal CT (median, 3.5 years v not reached, respectively; P < .001) and required earlier treatment intervention. In a multivariate analysis, only high ZAP-70 expression (relative risk = 3.60) and an abnormal abdominal CT (RR = 2.71) correlated with disease progression. Conclusion In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information.

Regulatory T-Cell Modulation by Green Tea in Chronic Lymphocytic Leukemia

2013 ◽  
Vol 26 (1) ◽  
pp. 117-125 ◽  
Author(s):  
G. D'arena ◽  
V. Simeon ◽  
L. De Martino ◽  
T. Statuto ◽  
F. D'auria ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Green Tea ◽  
Early Stage ◽  
Epigallocatechin Gallate ◽  
Serum Levels ◽  
Hematologic Malignancies ◽  
Absolute Number ◽  
Lymphocytic Leukemia ◽  
Antitumor Effects ◽  
Report Data

Regulatory T cells (Tregs) are considered to be key immunomodulatory cells of the immune system and are increased in chronic lymphocytic leukemia (CLL). Rai stage 0 identifies patients with early stage CLL for which there is no effective intervention at the present time and a “wait and see” policy is usually adopted. Some biological and clinical studies have reported that green tea constituents, such as epigallocatechin-gallate (EGCG), have antitumor effects on hematologic malignancies including CLL. We report data on a clinical trial in which green tea extracts were given orally to 12 patients with stage 0 CLL and 12 healthy subjects. Ten patients and 10 controls completed the 6-month scheduled therapy. Two patients and 2 controls stopped therapy within 1 month because of tachycardia and epigastralgia. Eight out 10 evaluable patients (80%) showed a reduction of lymphocytosis and absolute number of circulating Tregs, as well. One patient (10%) had a stabilization of lymphocytosis and a reduction of Tregs, and 1 patient (10%) showed an increase of both lymphocytosis and Tregs. Only the non-responding patient progressed after 5 months from the end of green tea administration and chemotherapy was given. Interestingly, both IL-10 and TGF-β serum levels declined throughout the green tea intake period, in both patients and controls. These data seem to indicate that green tea is able to modulate circulating Tregs in CLL patients with early stage of the disease. This can result in the control of lymphocytosis as well as in the prevention of disease progression.

scholarly journals Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG)

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2598-2607 ◽  
Author(s):  
Sonia Jaramillo ◽  
Andreas Agathangelidis ◽  
Christof Schneider ◽  
Jasmin Bahlo ◽  
Sandra Robrecht ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Multicenter Clinical Trials

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), higher CLL international prognostic index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (HR: 4.2, CI: 2-8.6, p<0.001), and shorter time-to-next-treatment (TTNT) in the advanced-stage cohort (HR: 2, CI: 1.2-3.3, p=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger age at diagnosis; in both cohorts, these patients showed a trend towards better outcomes versus other M-CLL. U-CLL subset #8 was associated with trisomy 12. Overall, this study shows that major stereotyped subsets have distinctive characteristics. For the first time in prospective multicenter clinical trials, subset # 2 appeared as an independent prognostic factor for earlier TTFT and TTNT and should be proposed for risk stratification of patients.

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