Chronic Lymphocytic Leukemia: From Genetics to Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 586

Special Issue Editor


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Guest Editor
Hematology Department, Hospital Universitario de la Princesa, Universidad Autonoma Madrid, 28006 Madrid, Spain
Interests: chronic lymphocytic leukemia treatment; biology

Special Issue Information

Dear Colleagues,

In recent years, targeted therapies have generated spectacular outcomes in clinical practice and have changed the treatment for patients with Chronic Lymphocytic Leukemia (CLL). Relevant insights are being unraveled from a biologic point of view, including the potential relevance of complex karyotype, novel genetic and molecular techniques, and the validation of those in the era of novel drugs. The current challenge for CLL treatment may include the lack of optimal evidence to recommend options or sequencing them in any given scenario. The purpose of this Special Issue is to understand the current pros and cons of different treatment options and explore new opportunities for effective anticancer therapies. This Special Issue welcomes reviews, as well as original research articles.

Dr. Javier Loscertales-Pueyo
Guest Editor

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Keywords

  • chronic lymphocytic
  • leukemia treatment
  • biology

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Published Papers (2 papers)

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Research

10 pages, 217 KB  
Article
Middle East Deployment and Lymphoid Malignancies in US Veterans: A Matched Case-Control Analysis
by Helen Ma and Pankaj Gupta
Cancers 2025, 17(19), 3161; https://doi.org/10.3390/cancers17193161 - 29 Sep 2025
Abstract
Background/Objective: US military personnel deployed to the Middle East were potentially subjected to harmful exposures, such as carcinogens from burn pits, which may increase the risk of lymphoid malignancies. Our objective was to determine the association between deployment and the risk of developing [...] Read more.
Background/Objective: US military personnel deployed to the Middle East were potentially subjected to harmful exposures, such as carcinogens from burn pits, which may increase the risk of lymphoid malignancies. Our objective was to determine the association between deployment and the risk of developing lymphoid malignancies. Methods: This was a retrospective nested matched case-control study from a cohort of 3.5 million veterans who enlisted in the military after September 2001 and were followed until death or last follow up through September 2024. Cases of lymphoid malignancies were identified by the VA Central Cancer Registry and controls were randomly selected from the same base cohort, matched by year of birth, year of enlistment, sex, race, and ethnicity. Exposure was defined as deployment to the Middle East as determined by identification on the VA Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) roster with confirmed dates of deployment or paystubs. Results: There were 1037 cases of lymphoid malignancies and 3572 matched controls. Deployment was not associated with a higher risk of developing lymphoid malignancies compared to non-deployment. Exposure to OEF/OIF was not associated with a higher risk of developing certain types of lymphoid malignancies. Conclusions: In this large, matched case-control study of US veterans, deployment to the Middle East was not associated with increased risk of developing lymphoid malignancies. While these findings do not support an increased lymphoid malignancy risk, important limitations remain, including the absence of detailed exposure and potential confounding variables. Prospective monitoring of specific types and doses of exposures during military deployment, development of lymphoid and other malignancies, and their underlying pathophysiology is indicated. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: From Genetics to Therapy)
10 pages, 383 KB  
Article
Venetoclax–Rituximab and Emerging Treatment Strategies After c-BTKi Exposure in Relapsed/Refractory CLL: A Real-World Cohort and Literature Overview
by Maria Dimou, Rodanthi Fioretzaki, Calliope Zerzi, Eliana Konstantinou, John V. Asimakopoulos, Maria Arapaki, Alexia Piperidou, Alexandros Machairas, Anastasia Kopsaftopoulou, Athanasios Liaskas, Aikaterini Bitsani, Marina Belia, Fotios Panitsas, Aikaterini Benekou, Panagiota Petsa, Eleni Plata, Panagiotis Tsaftaridis, Marina Siakantaris, Theodoros P. Vassilakopoulos, Panayiotis Panayiotidis and Maria K. Angelopoulouadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3159; https://doi.org/10.3390/cancers17193159 - 29 Sep 2025
Abstract
Background: Fixed-duration venetoclax plus rituximab (VR) is a standard therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). However, evidence supporting its use after covalent BTK inhibitor (c-BTKi) therapy is scarce in clinical trials and limited in real-world settings. Objectives: To assess the efficacy [...] Read more.
Background: Fixed-duration venetoclax plus rituximab (VR) is a standard therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). However, evidence supporting its use after covalent BTK inhibitor (c-BTKi) therapy is scarce in clinical trials and limited in real-world settings. Objectives: To assess the efficacy and safety of VR in a real-world cohort of patients with R/R CLL, including cBTKi-pretreated individuals, and to contextualize outcomes alongside published real-world studies and registrational trials of alternative therapies. Methods: We retrospectively analyzed 37 patients with R/R CLL treated with VR at our center between April 2018 and November 2024. Baseline characteristics, treatment responses, minimal residual disease (MRD), and adverse events were recorded. Survival was estimated using the Kaplan–Meier method. A structured review of relevant real-world evidence and pirtobrutinib clinical trials was also conducted. Results: Median age was 67 years; 35.1% had prior cBTKi exposure. The overall response rate (ORR) was 91.7% (22/24 evaluable patients), with 66.7% achieving complete remission (CR). Among evaluable c-BTKi-pretreated patients, the ORR was 87.5% (7/8) and the CR rate was 62.5%. Undetectable MRD (uMRD) rates were 78.6% in peripheral blood and 71.4% in bone marrow. Thirty-month progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were >90% for the whole cohort and for c-BTKi-pretreated patients. The most frequent adverse event was neutropenia grade ≥ 3, especially during combination therapy, which is easily managed with GCSF support. Conclusions: Our real-world evidence shows that VR is an effective and well-tolerated option even after c-BTKi therapy in R/R CLL. These data complement evidence from emerging therapies and inform post-c-BTKi treatment selection in clinical practice. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: From Genetics to Therapy)
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