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Original Article

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Blood Res 2021; 56(4):

Published online December 31, 2021

https://doi.org/10.5045/br.2021.2021102

© The Korean Society of Hematology

Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea

Jun Ho Yi1, Gyeong-Won Lee2, Ji Hyun Lee3, Kwai Han Yoo4, Chul Won Jung5, Dae Sik Kim6, Jeong-Ok Lee7, Hyeon Seok Eom8, Ja Min Byun9, Youngil Koh9, Sung Soo Yoon9, Jin Seok Kim10, Jee Hyun Kong11, Ho-Young Yhim12, Deok-Hwan Yang13, Dok Hyun Yoon14, Do Hyoung Lim15, Won-Sik Lee16, Ho-Jin Shin17

Author Info. +

1Division of Hematology-Oncology, Department of Medicine, Chung-Ang University Hospital, Seoul, 2Division of Hematology-Oncology, Department of Internal Medicine, Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, 3Department of Internal Medicine, Dong-A University College of Medicine, Busan, 4Division of Hematology-Oncology, Gachon University College of Medicine, Incheon, 5Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 6Department of Internal Medicine, Korea University Guro Hospital, Seoul, 7Division of Hematology-Oncology, Seoul National University Bundang Hospital, Seongnam, 8National Cancer Center, Goyang, 9Division of Hematology-Oncology, Seoul National University Hospital, 10Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 11Division of Hematology-Oncology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, 12Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, 13Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Gwangju, 14Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 15Division of Hematology-Oncology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, 16Inje University Busan Paik Hospital, 17Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea

Correspondence to : Ho-Jin Shin, M.D., Ph.D.
Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea
E-mail: hojinja@hanmail.net

Received: May 21, 2021; Revised: July 12, 2021; Accepted: August 25, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea.
Methods
The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/ rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%).
Results
The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P <0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively.
Conclusion
This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

Keywords Chronic lymphocytic leukemia, Outcomes, Asia

Article

Original Article

Blood Res 2021; 56(4): 243-251

Published online December 31, 2021 https://doi.org/10.5045/br.2021.2021102

Copyright © The Korean Society of Hematology.

Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea

Jun Ho Yi1, Gyeong-Won Lee2, Ji Hyun Lee3, Kwai Han Yoo4, Chul Won Jung5, Dae Sik Kim6, Jeong-Ok Lee7, Hyeon Seok Eom8, Ja Min Byun9, Youngil Koh9, Sung Soo Yoon9, Jin Seok Kim10, Jee Hyun Kong11, Ho-Young Yhim12, Deok-Hwan Yang13, Dok Hyun Yoon14, Do Hyoung Lim15, Won-Sik Lee16, Ho-Jin Shin17

1Division of Hematology-Oncology, Department of Medicine, Chung-Ang University Hospital, Seoul, 2Division of Hematology-Oncology, Department of Internal Medicine, Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, 3Department of Internal Medicine, Dong-A University College of Medicine, Busan, 4Division of Hematology-Oncology, Gachon University College of Medicine, Incheon, 5Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 6Department of Internal Medicine, Korea University Guro Hospital, Seoul, 7Division of Hematology-Oncology, Seoul National University Bundang Hospital, Seongnam, 8National Cancer Center, Goyang, 9Division of Hematology-Oncology, Seoul National University Hospital, 10Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 11Division of Hematology-Oncology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, 12Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, 13Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Gwangju, 14Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 15Division of Hematology-Oncology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, 16Inje University Busan Paik Hospital, 17Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea

Correspondence to:Ho-Jin Shin, M.D., Ph.D.
Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Medical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea
E-mail: hojinja@hanmail.net

Received: May 21, 2021; Revised: July 12, 2021; Accepted: August 25, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea.
Methods
The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/ rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%).
Results
The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P <0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively.
Conclusion
This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

Keywords: Chronic lymphocytic leukemia, Outcomes, Asia

Fig 1.

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Figure 1.Progression-free survival according to the first-line treatment regimens. Whole population (A), patients aged >65 years (B), patients aged ≤65 years (C).
Abbreviations: Cum survival, cumulative survival; FCR, fludarabine/cyclophosphamide/rituximab.
Blood Research 2021; 56: 243-251https://doi.org/10.5045/br.2021.2021102

Fig 2.

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Figure 2.Overall survival. Survival in the whole population (A), survival according to age (B), survival according to 17p deletion status (C) survival according to TP53 mutation status (D).
Abbreviations: CI, confidence interval; Cum survival, cumulative survival; OS, overall survival.
Blood Research 2021; 56: 243-251https://doi.org/10.5045/br.2021.2021102

Table 1 . Clinical and molecular features during first-line treatment (N=192)..

N (%)
Age (median, range)63 (34–87)
≤65 yr117 (60.9)
≥66 yr75 (39.1)
Sex
Male115 (59.9)
Female77 (40.1)
ECOG-PS
0–1179 (93.2)
2–413 (6.8)
Rai stage
01 (0.5)
I46 (24.0)
II46 (24.0)
III50 (26.0)
IV49 (25.5)
Binet stage
A22 (11.5)
B76 (39.6)
C94 (49.0)
Creatinine clearance (N=174)
~69 mL/min42 (24.1)
70 mL/min132 (75.9)
Largest tumor diameter
≤5 cm180 (93.7)
>5 cm12 (6.3)
FISH for del(11q) (N=51)
Normal43 (84.3)
Abnormal8 (15.7)
FISH for del(13q) (N=42)
Normal24 (57.1)
Abnormal18 (42.9)
FISH for del(17p) (N=46)
Normal39 (84.8)
Abnormal7 (15.2)
TP53 mutation analysis (N=66)
Mutated10 (15.2)
Wild-type56 (84.8)
FISH for del(17p) & TP53 mutation analysis (N=26)
Wild-type21 (80.8)
Del(17p)1 (3.8)
Mutated TP531 (3.8)
Del(17p) & mutated TP533 (11.5)
IgHV mutation analysis (N=10)
Mutated0 (0.0)
Wild-type10 (100.0)

Abbreviations: del, deletion; ECOG-PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; IgHV, immunoglobulin heavy chain gene..

Table 2 . Progression-free survival following first-line treatment according to clinical and molecular features..

NMedian PFS (95% CI)P
Del(17p)0.043
Present79.0 (5.1–12.9)
Absent3952.3 (32.5–72.1)
TP53 mutation0.005
Mutated1012.8 (3.9–21.5)
Wild type5644.9 (29.8–60.0)
Del(13q)0.133
Present1849.5 (45.9–53.1)
Absent2430.1 (11.7–48.5)
Del(11q)0.053
Present829.8 (2.0–57.6)
Absent4349.5 (31.2–67.8)
Age0.258
≤65 yr11767.5 (37.6–97.4)
≥66 yr7550.5 (34.8–66.2)
Binet stage0.156
A2247.9 (14.7–81.1)
B7655.6 (28.1–83.1)
C9458.4 (31.1–85.7)
Rai stage0.876
01NA
I4661.5 (46.6–76.4)
II4647.9 (32.3–63.5)
III50Not reached
IV4958.4 (39.6–77.2)
Treatment regimen0.001
FCR117Not reached
Obinutuzumab+Cbl30Not reached
Cbl2429.8 (9.8–49.8)
Patients aged ≤65 yr<0.001
FCR82Not reached
Obinutuzumab+Cbl521.4 (NE)
Cbl1729.8 (1.3–58.3)
Patients aged ≥66 yr0.890
FCR3549.5 (45.1–53.9)
Obinutuzumab+Cbl25Not reached
Cbl743.2 (0.9–85.5)

Abbreviations: Cbl, chlorambucil; CI, confidence interval; Del, deletion; FCR, fludarabine/cyclophosphamide/rituximab; NA, not applicable; PFS, progression-free survival..
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