From the Division of Hematology, Ohio State University, Columbus, OH.
Abstract
Objective: To describe the diagnosis and initial management of chronic lymphocytic leukemia (CLL), including first-line treatment options.
Methods: Case presentation and review of the literature.
Results: Most CLL patients demonstrate a chronic, relapsing and remitting course with intervals of months to years between treatments. Recent advances in genetic and molecular markers for risk stratification of CLL significantly impact how clinicians determine prognosis and predict response to treatment for patients with newly diagnosed disease. This information, along with patient factors such as age and health status, should be considered when formulating an initial treatment strategy. Combinations of chemotherapy and immunotherapy offer the longest progression-free survival and overall survival benefit yet reported. For elderly patients or those with significant comorbidities who may not tolerate standard chemoimmunotherapy, less intensive but still effective therapies now exist. Patients with the highest risk disease, such as those with deletions of chromosome 17p, respond poorly to conventional treatment and should be referred to experienced centers where investigational therapies and allogeneic stem cell transplantation are available.
Conclusion: Both disease characteristics and patient factors should guide the selection among the various effective therapies for CLL. While chemoimmunotherapy is the most effective treatment developed to date, its use may become less prevalent as newer agents are incorporated into initial and relapse treatment algorithms.
Chronic lymphocytic leukemia (CLL) is a chronic malignancy of B-lymphocytes demonstrating a heterogeneous clinical course ranging from indolent to more rapidly progressive. The chief clinical feature is an elevated peripheral blood lymphocyte count, and patients can demonstrate lymphadenopathy, splenomegaly, hepatomegaly, constitutional symptoms, and in late stages bone marrow failure. It is the most common leukemia among adults in the Western world, accounting for between 22% to 30% of new leukemia diagnoses worldwide [1]. Recent incidence rates in the United States are 3.83 cases per 100,000 person-years [2]. The incidence of CLL increases with age, and most new cases are diagnosed in persons 65 years of age or older [1,2]. As reported 5-year survival rates are between 68% and 81% with a median survival of 10 years in some series, the prevalence is significantly higher than the incidence [3]. However, this may even be an underestimate of the population burden of disease, as many cases are not reported to tumor registries [4].
Many patients with CLL are asymptomatic and do not require treatment until years after diagnosis. In these cases a watch and wait approach is taken. The typical natural history of CLL is characterized by periods of effective treatment when required, followed by treatment-free intervals of several years in many cases. However, this can be misleading, as the clinical course for any individual patient is highly variable. Development of cytogenetic and molecular testing has allowed for identification of patients with a higher risk of progression and lower response rates to traditional cytotoxic treatments [5]. For example, depending on chromosomal abnormalities present, median survival can vary from 32 to 133 months [3].
The assessment of underlying disease risk thus provides important information when considering a treatment approach and should be routinely performed for newly diagnosed patients. While the development of highly effective chemoimmunotherapy has allowed most groups of CLL patients to live for many years, some groups do not enjoy the same survival. Recent advances in CLL treatment seek to abrogate such adverse risk factors, thereby improving the survival for all patients with CLL. Given the expected survival of years for most CLL patients, frontline treatment planning must be done in the context of a long-term treatment strategy keeping the risk for late toxicities, such as secondary malignancies, in mind.
