What is the relationship between Chronic Lymphocytic Leukemia (CLL) and leukemia?

From the Guidelines

Chronic Lymphocytic Leukemia (CLL) is a distinct type of leukemia, characterized by the progressive accumulation of abnormal lymphocytes in the blood, bone marrow, and lymphoid tissues, and is the most common form of leukemia among adults in Western countries. The relationship between CLL and leukemia is that CLL is a subtype of leukemia, specifically a slow-growing cancer that affects white blood cells called lymphocytes in the bone marrow 1. In CLL, abnormal lymphocytes accumulate in the blood, bone marrow, and lymphoid tissues, crowding out healthy cells and impairing normal immune function. Unlike acute leukemias, CLL typically progresses slowly, and many patients don't require immediate treatment.

Key Characteristics of CLL

• CLL is the most common type of leukemia in adults in Western countries 1
• Abnormal lymphocytes accumulate in the blood, bone marrow, and lymphoid tissues, crowding out healthy cells and impairing normal immune function
• CLL typically progresses slowly, and many patients don't require immediate treatment
• Treatment decisions are based on disease staging, symptoms, and genetic markers, such as TP53 gene status and IGHV mutational status 1

Treatment Options for CLL

• Chemotherapy (fludarabine, cyclophosphicide) 1
• Immunotherapy (rituximab, obinutuzumab) 1
• Targeted therapies (ibrutinib, venetoclax) 1
• Combinations like FCR (fludarabine, cyclophosphamide, rituximab) 1
• Stem cell transplantation may be beneficial for some patients 1

Prognosis and Monitoring

• CLL cannot be cured in most cases but can often be managed as a chronic condition for many years 1
• Regular monitoring is essential as CLL can transform into more aggressive forms like Richter's syndrome 1
• Measurable residual disease (MRD) is a sensitive reflection of disease burden during and after fixed-duration treatment and has been correlated with progression-free survival (PFS) and overall survival (OS) 1

From the FDA Drug Label

IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) (1. 1). Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion (1.2).

Chronic Lymphocytic Leukemia (CLL) is a type of leukemia. The FDA drug label for ibrutinib 2 indicates that CLL is a specific condition for which the drug is approved, implying a direct relationship between CLL and leukemia.

From the Research

Relationship Between Chronic Lymphocytic Leukemia (CLL) and Leukemia

• Chronic Lymphocytic Leukemia (CLL) is a type of leukemia that is the most common in Western countries 3.
• CLL is a clonal malignancy of mature B cells that displays immense clinical heterogeneity 4.
• The disease typically occurs in elderly patients and has a highly variable clinical course 3, 5.
• Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells 3 or interfere with the regulation of proliferation and of apoptosis in clonal B-cells 5.

Diagnosis and Prognosis

• The diagnosis of CLL is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes 3, 5.
• Clinical staging systems, such as Rai and Binet, provide prognostic information by using the results of physical examination and blood counts 3, 4.
• Various biological and genetic markers, such as deletions of the short arm of chromosome 17 (del[17p]) and/or mutations of the TP53 gene, provide additional prognostic information 3, 5.

Treatment Options

• Only patients with active or symptomatic disease, or with advanced Binet or Rai stages require therapy 3, 5.
• Treatment options include a combination of venetoclax with obinutuzumab, ibrutinib monotherapy, or chemoimmunotherapy 3, 5.
• Patients with a del(17p) or TP53 mutation are usually resistant to chemotherapy and should be treated with targeted agents 3, 5.
• Combinations of targeted agents are now being investigated to create efficient, potentially curative therapies of CLL with fixed duration 5.

Transformation and Progression

• CLL can transform into a more aggressive lymphoma, known as Richter syndrome 6.
• Transdifferentiation of CLL to histiocytic/dendritic/Langerhans cell sarcomas has also been reported 6.
• "Accelerated" chronic lymphocytic leukemia/small lymphocytic lymphoma (A-CLL) is a rare histological variant of CLL/SLL that tends to exhibit an aggressive clinical behavior 7.