Molecular Features Underlying Racial Differences in Survival of Taiwanese Chronic Lymphocytic Leukemia Patients
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.
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
Inclusion Criteria:

 1. Patients with confirmed diagnosis of CLL, either histologically proven or with
 immunophenotypical pattern by flowcytometry

 2. The diagnosis of CLL was made after 2000; the complete medical history and the
 laboratory data are available for collections.

 3. Age of 20 or older

 4. Willing to cooperate with the informed consent procedure and the collections of blood
 samples and medical history.

 5. There are no limitations about organ functions, performance status, pregnancy or
 breast feeding status, or concomitant diseases or medicines.

 6. The patient's peripheral hemogram shows apparent leukocytosis (>15 k/μL) with
 lymphocytosis (lymphocytes+atypical lymphocytes >55%); the data should me within 3
 months before study enrollment.

 Exclusion Criteria:

 1. The patient's past history, including the diagnostic test results, the prior
 CLL-related treatment courses, the drug history, et.al, is not available.

 2. The patient cannot complete the informed consent procedures.

 3. The diagnosis is T-CLL, or the patients have been in complete remission without
 peripheral leukemia cells.