Chronic Lymphocytic Leukemia in Taiwan－Exploration of Epidemiology, Population Outcomes, Cytogenetics, and Novel Prognostic Markers
Date Issued
2014
Date
2014
Author(s)
Wu, Shang-Ju
Abstract
Introduction Chronic lymphocytic leukemia (CLL) is an indolent clonal lymphoid neoplasm. In Western countries, CLL is the most common leukemia in adults. However, CLL is much less prevalent in Eastern countries, including Taiwan. At present, data on CLL, including the clinical picture, epidemiology, and molecular studies, are mainly derived from western countries. Few studies have addressed the similarities and differences of CLL between Western and Eastern countries.
Patients and Methods Epidemiologic data for CLL in Taiwan, including the incidence rate and survival, were obtained from the Taiwan National Cancer Registry. The corresponding data for Caucasian Americans were obtained from the Surveillance, Epidemiology, and End Results database. The age-specific incidence rates of CLL for both populations were plotted by calendar year at diagnosis and by birth cohort. The individual effects of time period and birth cohort on the trends of the CLL incidence in both populations were analyzed using an age-period-cohort model. The relative survival (RS) of CLL patients in both populations was estimated as the observed survival among the cancer patients adjusted by the expected survival for a comparable group from the general population. Cytogenetic abnormalities (CA) were analyzed in a cohort of Taiwanese CLL patients (n=83) by both conventional cytogenetics (CG) and fluorescence in situ hybridization (FISH) and compared with data from Western countries. Furthermore, stem-cell factor (SCF) expression, a hypothesized prognostic marker, was also explored using immunohistochemical staining in bone marrow biopsy samples from CLL patients.
Results The age-adjusted incidence rate of CLL for Taiwanese continuously increased during a 20-year period while that for Caucasian Americans remained steady. A much stronger birth-cohort effect was identified in Taiwanese compared with Caucasian Americans. This effect corresponded to the westernization of the lifestyle in Taiwan since 1960. Overall, despite its indolent course, CLL drastically shortened patients’ life expectancy in both Taiwan and the US, and the decrease in RS in Taiwan was much larger than that in the US. Intriguingly, RS in Taiwan improved in patients diagnosed after 1995, a time period corresponding to the introduction of Taiwan National Health Insurance. This improvement was observed mainly in patients younger than 65 years while RS in older patients remained unchanged. After adjustment for age and gender effects, the diagnosis period remained an independent factor contributing to changes in RS in Taiwanese patients. CA were seen in 35 patients (42.2%) by CG analysis and 58 (69.9%) patients by FISH analysis Both CG and FISH showed that deletion of 17p or 11q was associated with poorer overall survival (OS), whereas isolated 13q deletion was associated with better OS. Trisomy 3 was found in five patients by CG, all of whom were in Binet stage A but had very poor OS; this prognostic impact was independent of other CA and Binet stages. Strong SCF expression in CLL cells in a small cohort seemed to predict poor OS, especially in patients with Binet B/C disease.
Conclusions In addition to the ethnic differences in the incidence, there was a distinct increased incidence trend of CLL in Taiwan. The strong birth-cohort effect underlying this trend suggests that lifestyle and environmental factors play a role in the development of CLL in Taiwanese. The survival of Taiwanese CLL patients was generally poor and inferior to that of US patients. However, the outcomes in younger patients have improved since 1995, possibly resulting from the availability of better medical care, suggesting that treatment advances have improved the outcome of CLL. Nevertheless, the survival of older patients remains poor and is in need of improvement. Although the disease incidences are different, the CA in Taiwanese patients with CLL are similar to those in the West; combined CG and FISH analysis is also able to predict outcomes in Taiwanese patients. The clinical significance of trisomy 3 as a poor prognostic factor warrants further validation. Finally, SCF expression might be a novel prognostic marker that warrants further verification with a larger cohort.
Subjects
慢性淋巴性白血病
發生率
年齡-年代-世代模型
細胞遺傳學異常
相對存活率
幹細胞因子(stem-cell factor)
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-103-D97421014-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):678266e0a7d92dc69a3d4982a5ba54e0