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Telomere length (TL) is a prognostic indicator in Caucasian chronic lymphocytic leukemia (CLL), but its significance in Asian CLL remains unknown. To investigate the prognostic significance of TL and its correlation with cytogenetic aberrations and somatic mutations, we analyzed TL measurements at the cellular level by interphase fluorescence in situ hybridization in patients with CLL in Korea. The present study enrolled 110 patients (41 females and 69 males) diagnosed with CLL according to the World Health Organization criteria (2001–2017). TLs of bone marrow nucleated cells at the single-cell level were measured by quantitative fluorescence in situ hybridization (Q-FISH) in 71 patients. The correlations of TL with clinical characteristics, cytogenetic aberrations, genetic mutations, and overall survival were assessed. The median value of mean TL in CLL patients (T/C ratio 7.46 (range 1.19–18.14) was significantly shorter than that in the normal controls (T/C ratio 15.28 (range 8.59–24.93) (p < 0.001). Shorter TLs were associated with complex karyotypes (p = 0.030), del(11q22) (p = 0.023), presence of deletion and/or mutation in ATM and/or TP53 (p = 0.019), and SH2B3 mutation (p = 0.015). A shorter TL was correlated with lower hemoglobin levels and adverse survival (mean TL < 9.35, p = 0.021). When the proportion of cells with extremely short TLs (< 7.61) was greater than 90%, CLL patients showed poor survival (p = 0.002). Complex karyotypes, TP53 mutation, and the number of mutated genes were determined to be significant adverse variables by multivariable Cox analysis (p = 0.011, p = 0.002, and p = 0.002, respectively). TL was attrited in CLL, and attrited telomeres were correlated with adverse survival and other well-known adverse prognostic factors. We infer that TL is an independent adverse prognostic predictor in Korean CLL. [ABSTRACT FROM AUTHOR]

Background: Medical care of cancer patients at the end-of-life is costly. This study aims to describe the monthly trends of EOL medical care, drug therapy, and chemotherapy costs per patient with cancer in the last year of life in the inpatients vs. outpatient setting for the 13 most prevalent cancers in Korea. Methods: Using the Health Insurance Review and Assessment Service (HIRA) database, we identified the patients who had been treated for the primary diagnoses of one of the 13 most prevalent cancers in Korea and died between January 1, 2013 and December 31, 2015. We calculated the mean monthly costs of medical care, drug therapy, and chemotherapy per patient in the last year of life by cancer site and patient setting (inpatient vs. outpatient). Results: For most cancers, the monthly inpatient costs per patient remain stable or increased gradually from 12 months to 3 months prior to death and then increased steeply from 2 months prior to death. The mean monthly inpatient costs per patient were highest for acute myeloid leukemia (AML) throughout the last year of life; all solid tumors had similar trends of monthly inpatient costs. The mean monthly inpatient costs for AML increased from $5,465 (SD, $5,248) in 12 months prior to death to $15,033 (SD, $11,864) in the last month. The monthly outpatient costs per patient showed similar, gradually decreasing trends for most cancers. The mean outpatient costs were highest for kidney cancer; the costs sharply decreased from $954 (SD, $1,346) in 12 months prior to death to $424 (SD, $736) in the last month. The proportion of inpatients receiving chemotherapy in the last month of life was highest for AML (77%), followed by liver cancer (67%) and breast cancer (56%). Conclusion: The monthly inpatient medical care costs per patient with cancer increased as the patient approached death, while the monthly outpatient costs decreased. A considerable proportion of inpatient received chemotherapy in the last month of life. Efforts are needed to optimize EOL care for cancer patients. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is extremely rare in Asian countries and there has been one report on genetic changes for 5 genes (TP53, SF3B1, NOTCH1, MYD88, and BIRC3) by Sanger sequencing in Chinese CLL. Yet studies of CLL in Asian countries using Next generation sequencing have not been reported. We aimed to characterize the genomic profiles of Korean CLL and to find out ethnic differences in somatic mutations with prognostic implications. We performed targeted sequencing for 87 gene panel using next-generation sequencing along with G-banding and fluorescent in situ hybridization (FISH) for chromosome 12, 13q14.3 deletion, 17p13 deletion, and 11q22 deletion. Overall, 36 out of 48 patients (75%) harbored at least one mutation and mean number of mutation per patient was 1.6 (range 0–6). Aberrant karyotypes were observed in 30.4% by G-banding and 66.7% by FISH. Most recurrent mutation (>10% frequency) was ATM (20.8%) followed by TP53 (14.6%), SF3B1 (10.4%), KLHL6 (8.3%), and BCOR (6.25%). Mutations of MYD88 was associated with moderate adverse prognosis by multiple comparisons (P = 0.055). Mutation frequencies of MYD88, SAMHD1, EGR2, DDX3X, ZMYM3, and MED12 showed similar incidence with Caucasians, while mutation frequencies of ATM, TP53, KLHL6, BCOR and CDKN2A tend to be higher in Koreans than in Caucasians. Especially, ATM mutation showed 1.5 fold higher incidence than Caucasians, while mutation frequencies of SF3B1, NOTCH1, CHD2 and POT1 tend to be lower in Koreans than in Caucasians. However, mutation frequencies between Caucasians and Koreans were not significantly different statistically, probably due to low number of patients. Collectively, mutational profile and adverse prognostic genes in Korean CLL were different from those of Caucasians, suggesting an ethnic difference, while profile of cytogenetic aberrations was similar to those of Caucasians. [ABSTRACT FROM AUTHOR]