Treatment of Younger Patients with Chronic Lymphocytic Leukemia

Abstract

Younger patients (defined as patients younger than 50 -55 years of age) represent a small group of newly diagnosed patients with chronic lymphocytic leukemia, accounting only for 10% to 20% of newly diagnosed cases. However, once these patients become symptomatic and require treatment, their life expectancy is significantly reduced. Therapeutic approaches for younger patients should be directed at improving survival by achieving a complete remission and, where possible, eradicating minimal residual disease. Chemoimmunotherapy combinations carry the highest response rates and are commonly offered to younger patients. Additional strategies that should be considered for younger patients include early referral for stem-cell transplantation and clinical trials of consolidation therapy to eliminate minimal residual disease. Epidemiology and Characteristics of Younger Patients with Chronic Lymphocytic LeukemiaChronic lymphocytic leukemia (CLL) is the most prevalent type of adult leukemia in the Western world. It is rare before the fourth decade of life, and its incidence increases exponentially after age 40. The upper age limit for definition of patients with CLL as "younger" has varied between 50 and 55 years in published reports, 1-5 but the designation usually refers to individuals in their 40s and 50s. Based on the National Cancer Institute's Surveillance and Epidemiology End Results (SEER) program estimates, 11% of the 15,490 patients diagnosed with CLL in 2009 in the United States were age 54 or younger 6 (Fig. 1). A similar proportion of younger patients have been reported in European studies. In an Italian series of 1011 patients with CLL between 1984 and 1994, 20% of the patients were 55 years of age or younger. 3 Similarly, 14.3% of the patients were younger than 50 years of age in a review of 929 patients in Spain between 1980 and 2008. 4 Published studies from Bennett 1 and Molica 5 in Europe also indicated that between 7% and 12% of their CLL population was younger than 50 years.Although younger patients represent a small group of newly diagnosed patients with CLL, they account for up to one-third of the patients that are referred to specialized medical centers. Based on a review of 3744 patients with CLL referred to the M.D. Anderson Cancer Center between 1970 and 2009, 37% of the patients were age 55 or younger (Fig. 2). Younger patients are more likely to participate in clinical trials for reasons that include better performance status, lower incidence of severe comorbidities, and a different attitude toward the diagnosis of CLL and available treatment options. Younger patients also experience significant psychosocial stress related to the diagnosis of CLL due to repercussions for work/employment status, impact on spouse/partners, and responsibility toward children and family.Several retrospective studies have summarized the clinical characteristics of younger patients with CLL. Differences in clinical features at presentation and in the traditional prognostic factors such as stage, lymphocyte-doubling...

Chronic lymphocytic leukemia in young (<= 55 years) patients: a comprehensive analysis of prognostic factors and outcomes

“…[2][3][4] Based on the National Cancer Institute's Surveillance and Epidemiology End Results (SEER) database, 11% of all patients diagnosed with CLL in 2009 were less than 55 years of age. 5 Populationbased studies from Europe also indicate that between 7% and 20% of patients with CLL are <55 years of age at diagnosis. 2,[6][7][8][9] These retrospective studies have described the clinical characteristics of younger patients with CLL, and have compared these to the characteristics of older CLL patients.…”

“…The threshold of ≤55 years was selected to classify age based on a similar cutoff used to define young CLL patients in historical studies. 5,7,29,30 Patients diagnosed with CLL between January 1995 and April 2012 and who fulfilled the 1996 criteria for CLL 31 and/or the World Health Organization (WHO) criteria for small lymphocytic lymphoma 32 were included in this analysis. Rai stage was ascertained within 12 months of the initial diagnosis.…”

Chronic lymphocytic leukemia in young individuals revisited

“…1 In studies from Europe and USA only 5%-11% of patients with CLL are younger than 50-55 years at diagnosis.…”

Long‐term molecular remission with lenalidomide treatment of relapsed chronic lymphocytic leukemia

“…In our case report, the molecular remission was demonstrated by nested PCR which showed a high sensitivity (10^−5 – 10^−6) . Eradication of MRD is considered the goal of therapy in young patients with CLL . In GCLLSG CLL8 trial, the absence of flow cytometric MRD prolonged PFS and OS , and the PFS of MRD‐negative patients was longer independently from the type and the number of chemotherapy cycles.…”