Molecular Features Underlying Racial Differences in Survival of Taiwanese Chronic Lymphocytic Leukemia Patients

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries; it is stratified as a subtype of indolent lymphoid malignancy with a long but slowly progressive nature history. However, the clinical course of CLL actually varies widely. Thus, many clinical and molecular features have been identified for outcome predictions. The accurate predictions of prognosis through those factors help for the decision making on the treatment, i.e. to treat patients of high risk of early progression or poor overall survival (OS) with alternative or investigational therapies, while to avoid unnecessary over-treatment for low-risk patients.

CLL is much less prevalent in Eastern countries; presently, most available data on CLL are derived mainly from Western countries. However, a previous report concerning the epidemiology of CLL in Taiwan revealed a drastic increase in the age-adjusted incidence of CLL, a trend not found in Western countries where the incidence rate of CLL remained steadily stable over time. In addition to this epidemiological difference, a population-based analysis has found the overall outcome of CLL, estimated by relative survivals, is steadily much poorer in Taiwanese patients than in US Caucasians. In another report about the cytogenetic profiles in a small cohort of CLL patients in Taiwan, a novel cytogenetic abnormality was found to correlate with poorer outcomes. These reports suggest the existence of ethnic differences in the disease natures of CLL between the East and the West.

To delineate the possible underlying racial differences, especially in the molecular prognostic profiles that might underlie the outcome disparity between Taiwanese and western CLL patients, a comprehensive surveillance of the molecular profiles for CLL in Taiwan is of importance. In this study, we are going to enroll around 250 CLL patients; their clinical parameters will be recorded, their blood samples will be collected for a panel of molecular and cytogenetic factor studies. The molecular markers to be tested in this project include (but not limited to) cytogenetic abnormalities by fluorescent-in-situ hybridization (FISH), immunoglobulin heavy chain variable region (IGHV) hypermutation status, gene mutations for Notch1, SF3B1, p53, MyD88, and BIRC3, and the expressions for ZAP70 and stem cell factor (SCF). These proposed markers include not only the conventional prognostic markers derived from Western studies, and also some novel explorations from our preliminary results, such as SCF and trisomy 3. Through this study, a comprehensive profile of CLL in Taiwan will be established to identify the characteristics of CLL in Taiwanese patients and to address the underlying factors of ethnic differences in the disease nature and outcomes of this disease.

Study milestone dates: Study Start (First Patient First Visit Date): July 2015，Recruitment end (Last Patient First Visit): July 2018.，Study end (Last Patient Last Visit): July 2020