Fast Facts: Chronic Lymphocytic Leukemia

By Toby A. Eyre, Parag Jasani and Lindsey E. Roeker

Chronic lymphocytic leukemia (CLL) is the most diagnosed leukemia in the Western world, accounting for approximately 25% of all new leukemia diagnoses. In recent years, remarkable progress has been made in our understanding of both the pathophysiology and genetics of CLL. While the disease generally affects older adults and initially follows an indolent course, cytogenetic and molecular profiling have helped to predict clinical outcomes. Greater prognostication, alongside the development of an increasing armamentarium of novel targeted therapies, has enabled us to provide more personalized management options for patients. Table of Contents • Epidemiology and etiology • Molecular biology and genetics • Diagnosis, staging and prognosis • Management • Research directions

• Language: English
• Publisher: S. Karger
• Release date: Jun 7, 2023
• ISBN: 9783318072303

Book preview

Introduction

Chronic lymphocytic leukemia (CLL) is the most diagnosed leukemia in the Western world, accounting for approximately 25% of all new leukemia diagnoses. In recent years, remarkable progress has been made in our understanding of both the pathophysiology and genetics of CLL. While the disease generally affects older adults and initially follows an indolent course, cytogenetic and molecular profiling have helped to predict clinical outcomes. Greater prognostication, alongside the development of an increasing armamentarium of novel targeted therapies, has enabled us to provide more personalized management options for patients.

Herein, we cover the epidemiology, etiology, diagnosis and staging of the disease, and the molecular and genetic aspects that underpin treatment and prognosis. Importantly, we provide a concise overview of treatment options, in both the front-line and relapsed/refractory settings, with particular focus on the novel targeted agents that have overcome many adverse prognostic factors, improving overall survival.

We also consider the role of allogeneic hematopoietic stem cell transplantation, which offers curative potential in selected young high-risk patients for whom targeted agents may eventually fail, and we provide guidance on the management of common complications associated with CLL, including tumor lysis syndrome, infection, autoimmune cytopenias and Richter transformation.

While huge strides have been made in the management of CLL, new approaches are still being developed to enhance the depth and durability of treatment responses. We look at these, and other important research directions, in the final chapter of the book.

We hope that this resource will provide all members of the multidisciplinary team who care for patients with CLL with a strong foundation for understanding, diagnosing and managing CLL in the present and future.

1Epidemiology and etiology

Definitions

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are monoclonal B-cell malignancies characterized by an accumulation of mature CD5+ B lymphocytes. CLL and SLL are leukemic and lymphomatous manifestations of the same biological entity. For patients with a persistent level of more than 5000 clonal B lymphocytes per microliter in the peripheral blood for at least 3 months, the diagnosis of CLL is made regardless of lymph-node involvement. For patients with SLL, clonal B lymphocytes drive lymphadenopathy and/or splenomegaly, but the number of clonal B lymphocytes in the peripheral blood is fewer than 5000 per microliter (Figure 1.1).¹,²

Monoclonal B-cell lymphocytosis (MBL) is a premalignant condition characterized by fewer than 5000 clonal B lymphocytes per microliter in the peripheral blood with no lymphadenopathy, splenomegaly or disease-related cytopenias.¹ Population-based screening studies show that the prevalence of MBL increases with age; it occurs in 0.2–0.3% of people under 40 years of age, but 5–9% of those over 60 years old.³,⁴ MBL carries a 1–2% risk of progression to CLL requiring therapy per year.⁵,⁶

Figure 1.1 Defining features of CLL, SLL and MBL.

Epidemiology

CLL is the most diagnosed leukemia in the Western world, accounting for approximately 25% of all new leukemia diagnoses.

Incidence and prevalence. Data from the Global Burden of Disease (GBD) study for 2019 reported 20 723 and 27 560 new cases of CLL in high-income North America and Western Europe, respectively. Globally, there were 103 467 people diagnosed with CLL in 2019.⁷ In the UK, there were around 3800 new cases per year in 2016–2018.⁸ Given the chronic nature of CLL, prevalence is much higher: for example, there were 200 766 people living with CLL in the USA in 2019.⁹

For the general population, the incidence is approximately 5 per 100 000 per year, though there is a male predominance in newly diagnosed patients.⁷–⁹ In the USA, CLL is most frequently diagnosed in White individuals compared with other ethnicities (Figure 1.2).⁹ The same has been shown in England, where 86% of cases of CLL in 2013–2017 occurred in White individuals compared with 1.9% in Asian and 0.9% in Black individuals.¹⁰

Figure 1.2 Rates of new cases in the USA per 100 000 men and women by race/ethnicity. Adapted from age-adjusted National Cancer Institute Surveillance, Epidemiology, and End Results data, 2015–2019.⁹ *Non-Hispanic.

Globally, age-standardized incidence of CLL increased by 155% between 1990 and 2019.⁷ However, in the USA, age-adjusted rates for new CLL diagnoses have been falling on average by 2.1% each year over the past decade.⁹

Incidence rises with age, and the median age at diagnosis is around 70 years. The GBD data showed that, worldwide, the highest incidence of new CLL cases was in people aged 60–75 years.⁷ US data have suggested racial differences in age at diagnosis, as Black patients were diagnosed at a median age of 67 years compared with 70 years for White