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Abstract Background Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non‐modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease. Method In 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non‐modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time‐to‐first‐treatment (TTFT) and adjusted all results for the CLL‐International Prognostic Index (CLL‐IPI). Results TTFT was shorter for patients with high/very high‐risk CLL‐IPI than those with low/intermediate risk CLL‐IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL‐IPI from any environmental characteristics assessed. Conclusions We found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment naïve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis.

AbstractChronic lymphocytic leukemia (CLL) is the most common leukemia in adults and characterized by a highly heterogeneous clinical course. The CLL-IPI and the OCLL-1 scores are among the best validated tools to predict time-to-first-treatment. In both models, elevated beta-2-microglobulin plasma level (B2M) is an independent prognostic factor. Yet, B2M is commonly increased in patients with chronic kidney disease (CKD) per se and both models were not adjusted for CKD. We analyzed the clinical outcomes of 297 treatment-naive CLL patients between 2000 and 2022. B2M was more frequently elevated in CKD patients and lost prognostic significance at the threshold > 2.5 mg/L. Both CLL-IPI and OCLL-1 failed to facilitate prognostic segregation in CKD patients. 22.2% of CKD patients were assigned to a higher CLL-IPI risk group due to elevated B2M. Our results suggest that both models overestimate the risk for disease progression and need to be interpreted with caution in CKD patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine validity of the CLL International prognostic index (IPI) scoring system in Pakistani chronic lymphocytic leukemia patients, as the validity and universal applicability of various prognostic scoring systems such as the CLL-IPI remains a challenge, particularly in under-developed countries like Pakistan. Methods: This prospective single center study was conducted at Department of Hematology, University of Health Sciences, Lahore and included sixty patients with CLL diagnosed between July, 2019 to July, 2022. Patients were followed for a period of two years and 02 year overall survival (OS) was noted. Risk stratification was conducted according to CLL-IPI prognostic model. Results: Among 60 patients, the mean age was 60±11years. Advanced Binet stage B+C and elevated β2-microglobulin >3.5mg/L was observed in 73.3% and 38.3% patients respectively. The estimated median 02 years OS was 16.5 months (95% CI: 10-20 months). In total, 40 of 60 CLL patients (67%) were accessible for follow-up analyses. For the present CLL cohort, 25% patients (n = 10) were classified as CLL-IPI low risk and intermediate risk group, 35% (n = 14) as high risk and 15% (n = 06) as very high-risk group. However, this classification of patients according to CLL-IPI did not yield significant differences in terms of OS (p = 0.24), although the median OS of CLL-IPI very high-risk group was noted as only six months and was not reached for low and intermediate risk groups. Conclusion: To conclude, clinical validation of CLL-IPI scoring system could not be established for the present CLL cohort and needs to be evaluated in further studies with larger sample size. [ABSTRACT FROM AUTHOR]

Introduction: The Chronic Lymphocytic Leukemia International Prognostic Index (CLL-IPI) is a powerful prognostic tool validated in multiple Western populations. However, its utility in the young Middle Eastern population is unknown. Methodology: We conducted a retrospective analysis of 152 unselected patients with chronic lymphocytic leukemia (CLL) diagnosed between 2008 and 2022 at the Kuwait Cancer Control Center, which serves as the sole cancer center in Kuwait. The evaluation of the CLL-IPI was based on the assessment of event-free survival (EFS) across the entire cohort. Subsequently, we compared the CLL-IPI with the International Prognostic Score for Early-stage patients (IPS-E) in order to predict the time to first treatment specifically within the subgroup of patients diagnosed with early-stage disease. Results: The median age of the study cohort was 59.9 years (IQR, 53.1–68.8). The 5-year EFS rates for the low, intermediate, and high/very high-risk categories were approximately 82%, 34%, and 23%, respectively, p < 0.001 (C-statistic = 0.67). On multivariate analysis, advanced stage and unmated IGHV status were independent prognostic factors of EFS. In those with early-stage disease, cumulative 5-year treatment incidence rates for the low, intermediate, and high/very high-risk categories based on the CLL-IPI score were approximately 8%, 55%, and 55%, respectively, p = 0.001 (C-statistic = 0.70). However, based on the IPS-E score, the cumulative 5-year treatment incidence rates for the low, intermediate, and high-risk categories were approximately 0%, 10%, and 60%, respectively, p < 0.001 (C-statistic = 0.73). Conclusions: The CLL-IPI and the IPS-E are valid stratification tool in our young Middle Eastern population. [ABSTRACT FROM AUTHOR]

Hypocholesterolaemia is associated with elevated cancer risk and mortality, yet the relation between chronic lymphocytic leukaemia (CLL) and serum lipid profile remains unclear. Our study aims to evaluate the prognostic value of cholesterol levels in CLL and develop a prognostic nomogram that incorporates lipid metabolism. We enrolled 761 newly diagnosed CLL patients and separated them into either derivation (n = 507) or validation (n = 254) cohorts. The prognostic nomogram was constructed through multivariate Cox regression analyses, with performance evaluated using C-index, the area under the curve, calibration, and decision curve analyses. Decreased total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at diagnosis were significantly associated with worse time to first treatment (TTFT) and cancer-specific survival (CSS), and simultaneously, low HDL-C with low LDL-C was identified as an independent prognostic indicator for both TTFT and CSS. CLL patients achieving complete or partial remission post-chemotherapy had significantly increased TC, HDL-C, and LDL-C levels compared with the baseline, and post-therapeutic HDL-C and LDL-C elevation correlated with favourable survival. The prognostic nomogram augmenting the CLL international prognostic index with low cholesterol levels yielded higher predictive accuracy and discrimination capacity for both 3-year and 5-year CSS. In conclusion, cholesterol profiles can be used as a cheap and readily accessible tool for predicting prognosis in CLL practice. [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non-modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease., Method: In 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non-modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time-to-first-treatment (TTFT) and adjusted all results for the CLL-International Prognostic Index (CLL-IPI)., Results: TTFT was shorter for patients with high/very high-risk CLL-IPI than those with low/intermediate risk CLL-IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL-IPI from any environmental characteristics assessed., Conclusions: We found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment naïve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis., Competing Interests: Karin E. Smedby: received honoraria from Celgene and research support from Janssen. Ingrid Glimelius received honoraria from Janssen and participated in a real‐world data study sponsored by Takeda. Richard Rosenquist received honoraria from AbbVie, AstraZeneca, Illumina, Janssen, and Roche. DSMC (Data Safety Monitoring Committee) for Agios Pharm, Astra Zeneca, Cytomx Therapeutics, Rigel. Advisory Board for Cytomx Therapy, Pharmacyclics, Dava Oncology, Juno Therapeutics, Oncotracker, and Abbvie. Sameer A. Parikh: Research funding has been provided to the institution (Mayo Clinic) from Janssen, AstraZeneca, Merck, and Genentech for clinical studies in which Sameer A. Parikh is a principal investigator. Honoraria has been provided to the institution (Mayo Clinic) from Pharmacyclics, Merck, AstraZeneca, Janssen, Genentech, Amgen, MingSight Pharmaceuticals, TG Therapeutics, Novalgen Limited, Kite Pharma, and AbbVie for Sameer A. Parikh's participation in consulting activities/advisory board meetings. Carsten Utofth Niemann received honoraria and/or research support from AstraZeneca, Abbvie, Janssen, Beigene, Genmab, CSL Behring, Takeda, Octapharma, and MSD. The rest of the authors declare no conflict of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

The CLL-IPI is a risk-weighted prognostic model for previously untreated patients with chronic lymphocytic leukemia (CLL), but has not been evaluated in patients with relapsed CLL or on novel therapies. We evaluated the CLL-IPI in 897 patients with relapsed/refractory CLL in 3 randomized trials testing idelalisib (PI3Kδ inhibitor). The CLL-IPI identified patients as low (2.2%), intermediate (12.8%), high (48.7%), and very high (36.2%) risk and was prognostic for survival (log-rank p <.0001; C-statistic 0.706). Of CLL-IPI factors, age >65, β2-microglobulin >3.5mg/L, unmutated immunoglobulin heavy chain variable region gene, and deletion 17p/TP53 mutation were independently prognostic, but Rai I-IV or Binet B/C was not. The CLL-IPI is prognostic for survival in relapsed CLL and with idelalisib therapy. However, low/intermediate risk is uncommon, and regression parameters of individual factors in this risk-weighted model appear different in relapsed CLL. Reassessment of the weighting of the individual variables might optimize the model in this setting. [ABSTRACT FROM AUTHOR]

Prognostic indices combining several clinical and laboratory parameters have been proposed for prognostication in chronic lymphocytic leukemia (CLL). Recently, international consortium on CLL proposed an international prognostic index (CLL-IPI) integrating clinical, molecular, and genetic parameters. The present study was designed to evaluate the reproducibility of CLL-IPI in Indian CLL cohort. The prognostic ability of CLL-IPI in terms of overall survival (OS) and time to first treatment (TTFT) was investigated in treatment-naive CLL patients and also compared with other existing prognostic scores. For assigning scores, clinical and laboratory details were obtained from medical records, and IGHV gene mutation status, β2-microglobulin levels, and copy number variations were determined using c-DNA, ELISA, and multiplex ligation-dependent probe amplification (MLPA), respectively. The scores were generated as per the weighted grades assigned to each variable involved in score categorization. The predictive value of prognostic models was assessed and compared using Harrell's C-index and Akaike's information criterion (AIC). Stratification of patients according to CLL-IPI yielded significant differences in terms of OS and TTFT (p < 0.001). Comparative assessment of scores for OS suggested better performance of CLL-IPI (C = 0.64, AIC = 740) followed by Barcelona-Brno (C = 0.61, AIC = 754) and MDACC score (C = 0.59, AIC = 759). Comparison of predictive value of prognostic scores for TTFT illustrated better performance of CLL-IPI (C = 0.72, AIC = 726) followed by Barcelona-Brno (C = 0.68, AIC = 743), modified GCLLSG (C = 0.66, AIC = 744), and O-CLL1 index (C = 0.55, AIC = 773). The results suggest better performance of CLL-IPI in terms of both OS and TTFT as compared to other available scores in our cohort. [ABSTRACT FROM AUTHOR]

The article discusses a study on the predictive value of the chronic lymphocytic leukemia-international prognostic index (CLL-IPI), determined at the time of first treatment, for progression-free survival (PFS) in CLL patients who underwent different frontline chemo-immunotherapy treatment regimens. Topics include the treatment regimens undergone by the patients, capability of the CLL-IPI score to predict PFS, and prognostic power of CLL-IPI when evaluated at the time of first-line therapy.

Objective: To analyze the factors affecting the long-term survival of patients with chronic lymphocytic leukemia (CLL)., Methods: The clinical data of 101 newly diagnosed CLL patients from January 2010 to January 2021 were retrospectively analyzed. Rai and Binet staging systems were used for clinical staging, and CLL-IPI was used for risk stratification of the patients., Results: There were 61 males and 40 females, the median age at diagnosis was 64 (28-84) years, the median PFS (progression-free survival) was 77（66-88） months, the 2-year and 5-year PFS rates were 85% and 64% respectively. The median OS (overall survival) was 108（103-112） months, the 5-year and 9-year OS rates were 74% and 46% respectively. Univariate analysis showed that high or very high risk of CLL-IPI, TP53 aberrations, del(17p), need for treatment and different treatment methods were the factors affecting OS ( P <0.05); high or very high risk of CLL-IPI, TP53 aberrations, del(17p) and complex karyotype were associated with PFS ( P <0.05). By X-tile analysis, it was found that the white blood cell count, the absolute neutrophil count, the hemoglobin level, and β 2 -microglobulin level were associated with OS ( P <0.05); the white blood cell count, the absolute lymphocytes count, the hemoglobin level, the platelet count, and the lactate dehydrogenase level were associated with PFS（P＜0.05）., Conclusion: The high or very high risk of CLL-IPI, TP53 aberrations, del(17p), need for treatment and different treatment methods are the factors affecting the OS of CLL patients, and high or very high risk of CLL-IPI, TP53 aberrations, del(17p) and complex karyotype are the factors affecting the PFS of CLL patients.

Background: The discovery of new biologic variables with high prognostic effect has been accompanied by the emergence of different prognostic indexes (PIs) to assess the time to first treatment in patients with early-stage (Binet A) chronic lymphocytic leukemia (CLL). The present study compared the prognostic value of 5 PIs: CLL international prognostic index (CLL-IPI), Barcelona-Brno, international prognostic score-A (IPS-A), CLL-01, and a tailored approach., Patients and Methods: We applied the 5 PIs to a cohort of 428 unselected patients with Binet A CLL from a multicenter Spanish database with clinical and biologic information available. The predictive value of the scores was assessed using Harrell's concordance index (C index) and area under the receiver operating characteristic curve (AUC)., Results: We found a significant association between time to first treatment and risk subgroups for all 5 PIs used. The most accurate PI was the IPS-A (C-index, 0.72; AUC, 0.76), closely followed by CLL-01 (C-index, 0.69; AUC, 0.70), CLL-IPI (C-index, 0.69; AUC, 0.69), Barcelona-Brno (C-index, 0.67; AUC, 0.69), and the tailored approach (C-index, 0.61 and 0.58; AUC, 0.58 and 0.54)., Conclusions: The concordance between the PIs was low (44%), suggesting that although all these PIs improve clinical staging and help physicians in routine clinical practice, it will be necessary to harmonize larger cohorts of patients to define the best PI for treatment decision-making in the real world., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Chronic lymphocytic leukemia (CLL) is the most frequent adult leukemia in western countries, but it is rare in Japan. Several mutations have been identified in patients with CLL using next-generation sequencing, but disease-specific mutations were not found. Some mutations, such as those in TP53, NOTCH1, SF3B, and BIRC3 are useful for risk stratification and prognosis prediction in patients with CLL. Strategies for treating CLL are rapidly evolving, with targeted agents such as the B-cell receptor signaling pathway inhibitors (ibrutinib, idelalisib), novel anti-CD20 monoclonal antibody (obinutuzumab), and Bcl-2 inhibitor (venetoclax) being approved by the US Food and Drug Administration. Although key drugs such as chlorambucil and rituximab cannot be used in Japan, others such as ibrutinib and bendamustine were recently approved for CLL treatment in Japan.