Abstract
Despite impressive therapeutic progress represented by the advent of chemoimmunotherapy, chronic lymphocytic leukemia (CLL) remains incurable by conventional modalities. Refractory CLL defined by non-response to treatment or relapse/progression within 6 months is associated with multiple unfavourable prognostic factors such as p53 pathway disruption, deteriorating patient condition, increased risk of severe infections, and poor response to treatment, resulting in a very short overall survival. Therefore, refractory CLL represents a highly challenging situation for the hematologist as well as the patient. The amount and quality of data on refractory CLL are rather limited as clinical trials usually combine patients with relapsed and refractory disease. Therapeutic options for refractory CLL include alemtuzumab, ofatumumab, fludarabine- and bendamustine-based regimens, platinum-based aggressive protocols and high-dose corticosteroids combined with monoclonal antibodies. The recent introduction of ibrutinib and idelalisib, small molecules interfering with B-cell receptor pathways, revolutionized the treatment of refractory CLL by the novel concept of long-term, oral treatment leading to impressive progression-free and overall survival improvement. Allogeneic stem cell transplantation is still considered the only option with curative potential. This review focuses on the currently available therapeutic strategies for refractory CLL.
Keywords: Chronic lymphocytic leukemia, refractory, ibrutinib, idelalisib, rituximab, ofatumumab, allogeneic stem cell transplantation.
Current Cancer Drug Targets
Title:Refractory Chronic Lymphocytic Leukemia: A Therapeutic Challenge
Volume: 16 Issue: 8
Author(s): Lukas Smolej
Affiliation:
Keywords: Chronic lymphocytic leukemia, refractory, ibrutinib, idelalisib, rituximab, ofatumumab, allogeneic stem cell transplantation.
Abstract: Despite impressive therapeutic progress represented by the advent of chemoimmunotherapy, chronic lymphocytic leukemia (CLL) remains incurable by conventional modalities. Refractory CLL defined by non-response to treatment or relapse/progression within 6 months is associated with multiple unfavourable prognostic factors such as p53 pathway disruption, deteriorating patient condition, increased risk of severe infections, and poor response to treatment, resulting in a very short overall survival. Therefore, refractory CLL represents a highly challenging situation for the hematologist as well as the patient. The amount and quality of data on refractory CLL are rather limited as clinical trials usually combine patients with relapsed and refractory disease. Therapeutic options for refractory CLL include alemtuzumab, ofatumumab, fludarabine- and bendamustine-based regimens, platinum-based aggressive protocols and high-dose corticosteroids combined with monoclonal antibodies. The recent introduction of ibrutinib and idelalisib, small molecules interfering with B-cell receptor pathways, revolutionized the treatment of refractory CLL by the novel concept of long-term, oral treatment leading to impressive progression-free and overall survival improvement. Allogeneic stem cell transplantation is still considered the only option with curative potential. This review focuses on the currently available therapeutic strategies for refractory CLL.
Export Options
About this article
Cite this article as:
Smolej Lukas, Refractory Chronic Lymphocytic Leukemia: A Therapeutic Challenge, Current Cancer Drug Targets 2016; 16 (8) . https://dx.doi.org/10.2174/1568009616666160408150032
DOI https://dx.doi.org/10.2174/1568009616666160408150032 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Targeting the Perpetrator: Breast Cancer Stem Cell Therapeutics
Current Drug Targets ChemoImmunoModulation: Immune Regulation by the Antineoplastic Chemotherapeutic Agents
Current Medicinal Chemistry Protective Effect of Heat Shock Proteins in the Nervous System
Current Neurovascular Research Noxa: Role in Cancer Pathogenesis and Treatment
Current Cancer Drug Targets ADAM Metalloproteinases as Potential Drug Targets
Current Medicinal Chemistry Bioactives in Disease Prevention and Health Promotion: Exploiting Combinatorial Effects
Current Bioactive Compounds Exploring Confluence-Related Signalling to Modulate the Expression of Oct4 – A Role in Facilitating Mouse Somatic Cell Reprogramming?
Current Stem Cell Research & Therapy Advances in Fish Cytokine Biology Give Clues to the Evolution of a Complex Network
Current Pharmaceutical Design Rhenium-188 and Copper-67 Radiopharmaceuticals for the Treatment of Bladder Cancer
Mini-Reviews in Medicinal Chemistry Designed Multiple Ligands for Cancer Therapy
Current Medicinal Chemistry Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies
Recent Patents on Anti-Cancer Drug Discovery Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates
Current Topics in Medicinal Chemistry Drugs that Inhibit Tubulin Polymerization: The Particular Case of Podophyllotoxin and Analogues
Current Medicinal Chemistry - Anti-Cancer Agents Targeting PDK1 in Cancer
Current Medicinal Chemistry OX40 and OX40L Interaction in Cancer
Current Medicinal Chemistry Serine-Threonine Protein Kinases CK1, CK2 and GSK3 in Normal and Malignant Haematopoiesis
Current Signal Transduction Therapy LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery
Current Pharmaceutical Design A Long Time History of a Mediastinal Fibrosis with Triple Vascular Stenosis
Current Respiratory Medicine Reviews Targeting Proteasomes with Naturally Occurring Compounds in Cancer Treatment
Current Cancer Drug Targets The Need for Calcium Channels in Cell Proliferation
Recent Patents on Anti-Cancer Drug Discovery