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    Fast Facts: Chronic Lymphocytic Leukemia
    Fast Facts: Chronic Lymphocytic Leukemia
    Fast Facts: Chronic Lymphocytic Leukemia
    Ebook89 pages52 minutes

    Fast Facts: Chronic Lymphocytic Leukemia

    By T.A. Eyre, P. Jasani and L.E. Roeker

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    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. 'Fast Facts: Chronic Lymphocytic Leukemia' covers the epidemiology, etiology, diagnosis and staging of the disease, and the molecular and genetic aspects that underpin treatment and prognosis. It provides 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. Table of Contents: • Epidemiology and etiology • Molecular biology and genetics • Diagnosis, staging and prognosis • Management • Research directions
    LanguageEnglish
    PublisherS. Karger
    Release dateFeb 11, 2022
    ISBN9783318069747
    Fast Facts: Chronic Lymphocytic Leukemia

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      Book preview

      Fast Facts - T.A. Eyre

      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. The American Cancer Society estimates there will be 21 250 new cases of CLL in the USA in 2021, and 4320 deaths attributable to the disease.⁷ Given the chronic nature of CLL, prevalence is much higher: there were 186 422 people living with CLL in the USA in 2017.⁸ Globally, it is estimated that 191 000 people were diagnosed with CLL and 61 000 died of CLL in 2015.⁹

      For the general population, the incidence is approximately 5 per 100 000 per year, though incidence varies by sex and ethnicity.⁸ There is a male predominance in newly diagnosed patients, with 1.9 men to every 1 woman diagnosed.¹⁰ CLL is most frequently diagnosed in white individuals (7.3 and 3.9 per 100 000 men and women per year, respectively) compared with other ethnicities (Figure 1.2).

      Figure 1.2 Rates of new cases per 100 000 men and women by ethnicity. Adapted from age-adjusted National Cancer Institute Surveillance, Epidemiology, and End Results data, 2014–2018.⁸

      Age-adjusted rates for new CLL diagnoses and CLL-related deaths have been falling, on average, by 1.4% and 3.1%, respectively, in the past decade in the USA.⁸ Globally, however, age-standardized incidence nearly doubled between 1990 and 2017.¹¹

      Incidence rises with age, and the median age at diagnosis is 70 years. In total, 90% of patients diagnosed with CLL are over 50 years old and incidence exceeds 30 per 100 000 per year for those

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