Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study
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Background/Aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). Conclusions: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.
Abstract
Background/Aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). Conclusions: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.
참고문헌 (27)
- Matutes E, "The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL", Leukemia, 8, pp.1640~1645 (1994)
- Hallek M, "Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines", Blood, 111, pp.5446~5456 (2008)
- Binet JL, "A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis", Cancer, 48, pp.198~206 (1981)
- Rai KR, "Clinical staging of chronic lymphocytic leukemia", Blood, 46, pp.219~234 (1975)
- Hamblin TJ, "Unmutated Ig V(H)genes are associated with a more aggressive form of chronic lymphocytic leukemia", Blood, 94, pp.1848~1854 (1999)
- Pflug N, "Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia", Blood, 124, pp.49~62 (2014)
- Dohner H, "Genomic aberrations and survival in chronic lymphocytic leukemia", N Engl J Med, 343, pp.1910~1916 (2000)
- 전영우, "Chronic lymphocytic leukemia: a clinical review including Korean cohorts", The Korean Journal of Internal Medicine, 31(3), pp.433~443 (2016), 대한내과학회
- Yang SM, "The mystery of chronic lymphocytic leukemia (CLL): why is it absent in Asians and what does this tell us about etiology, pathogenesis and biology?", Blood Rev, 29, pp.205~213 (2015)
- Yoon SO, "Distribution of lymphoid neoplasms in the Republic of Korea : analysis of 5318 cases according to the World Health Organization classification", Am J Hematol, 85, pp.760~764 (2010)
- Chihara D, "Differences in incidence and trends of haematological malignancies in Japan and the United States", Br J Haematol, 164, pp.536~545 (2014)
- Jang MA, "Chronic lymphocytic leukemia in Korean patients : frequent atypical immunophenotype and relatively aggressive clinical behavior", Int J Hematol, 97, pp.403~408 (2013)
- 이혜원, "Nationwide Statistical Analysis of Lymphoid Malignancies in Korea", Cancer Research and Treatment, 50(1), pp.222~238 (2018), 대한암학회
- Gunawardana C, "South Asian chronic lymphocytic leukaemia patients have more rapid disease progression in comparison to White patients", Br J Haematol, 142, pp.606~609 (2008)
- Agrawal N, "Chronic lymphocytic leukemia in India : a clinico-hematological profile", Hematology, 12, pp.229~233 (2007)
- Eichhorst B, "First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia(CLL10) : an international, open-label, randomised, phase3, non-inferiority trial", Lancet Oncol, 17, pp.928~942 (2016)
- Woyach JA, "Chronic lymphocytic leukemia : recent progress and current challenges", Semin Oncol, 43, pp.199~200 (2016)
- Walter HS, "New agents to treat chronic lymphocytic leukemia", N Engl J Med, 374, pp.2185~2186 (2016)
- Vela CM, "Ibrutinib for treatment of chronic lymphocytic leukemia", Am J Health Syst Pharm, 73, pp.367~375 (2016)
- Zenz T, "TP53 mutation and survival in chronic lymphocytic leukemia", J Clin Oncol, 28, pp.4473~4479 (2010)
- Rossi D, "The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13 : implications for overall survival and chemorefractoriness", Clin Cancer Res, 15, pp.995~1004 (2009)
- International CLL-IPI working group, "An international prognostic index for patients with chronic lymphocytic leukaemia(CLL-IPI) : a meta-analysis of individual patient data", Lancet Oncol, 17, pp.779~790 (2016)
- Le Bris Y, "Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia", Hematol Oncol, 35, pp.664~670 (2017)
- Rigolin GM, "In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristics", Br J Haematol, 181, pp.229~233 (2018)
- Herling CD, "Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucil-based chemotherapy or chemoimmunotherapy", Blood, 128, pp.395~404 (2016)
- Wierda WG, "Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia", Blood, 109, pp.4679~4685 (2007)
- Hallek M, "iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL", Blood, 131, pp.2745~2760 (2018)