Research Papers:

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study

Seok Jin Kim, Jun Sik Hong, Myung Hee Chang, Jeong-A Kim, Jae-Yong Kwak, Jin Seok Kim, Dok Hyun Yoon, Won Sik Lee, Young Rok Do, Hye Jin Kang, Hyeon-Seok Eom, Yong Park, Jong-Ho Won, Yeung-Chul Mun, Hyo Jung Kim, Jung Hye Kwon, Jee Hyun Kong, Sung Yong Oh, Sunah Lee, Sung Hwa Bae, Deok-Hwan Yang, Hyun Jung Jun, Yang Soo Kim, Hwan Jung Yun, Soon Il Lee, Min Kyoung Kim, Eun Kyung Park, Won Seog Kim and Cheolwon Suh _

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Oncotarget. 2016; 7:72033-72043. https://doi.org/10.18632/oncotarget.12459

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Seok Jin Kim1,*, Jun Sik Hong2,*, Myung Hee Chang3, Jeong-A Kim4, Jae-Yong Kwak5, Jin Seok Kim6, Dok Hyun Yoon7, Won Sik Lee8, Young Rok Do9, Hye Jin Kang10, Hyeon-Seok Eom11, Yong Park12, Jong-Ho Won13, Yeung-Chul Mun14, Hyo Jung Kim15, Jung Hye Kwon16, Jee Hyun Kong17, Sung Yong Oh18, Sunah Lee19, Sung Hwa Bae20, Deok-Hwan Yang21, Hyun Jung Jun22, Yang Soo Kim23, Hwan Jung Yun24, Soon Il Lee25, Min Kyoung Kim26, Eun Kyung Park27, Won Seog Kim1, Cheolwon Suh7

1Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

3Department of Hematology-Oncology, National Health Insurance Service Ilsan Hospital, Goyang, Gyeongki-do, Korea

4Department of Internal Medicine, St. Vincent's Hospital, the Catholic University of Korea, Seoul, Korea

5Department of Internal Medicine, Chonbuk National University Medical School & Hospital, Jeonju, South Korea

6Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

8Department of Internal Medicine, Inje University College of Medicine, Inje University Busan Paik Hospital, Gaegumdong, Busanjingu, Busan, Republic of Korea.

9Division of Hematology-Oncology, Department of Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea

10Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

11Hematology-Oncology Clinic, National Cancer Center, Goyang-city, Korea

12Department of Internal Medicine, Korea University Anam Hospital, College of Medicine, Seoul, Korea

13Department of Internal Medicine, Soon Chun Hyang University, Seoul, Korea

14Department of Internal Medicine, Ewha Womans University, Seoul, Korea

15Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Chucheon, Korea

16Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea

17Division of Hematology-Oncology, Department of Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Korea

18Department of Internal Medicine, Dong-A University Hospital, Busan, Korea

19Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea

20Department of Internal Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea

21Department of Hemato-oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Korea

22Department of Internal Medicine, Seoul Medical Center, Seoul, Korea

23Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea

24Department of Hemato-oncology, Chungnam National University Hospital, Daejeon, Korea

25Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea

26Department of Medicine, Yeungnam University College of Medicine, Daegu, Korea

27Department of Internal Medicine, Chung Ang University, Seoul, Korea

*These authors contributed equally to this work as co-first authors

Correspondence to:

Won Seog Kim, email: [email protected]

Cheolwon Suh, email: [email protected]

Keywords: diffuse large B-cell lymphoma, central nervous system, prognosis, lactate dehydrogenase

Received: August 11, 2016     Accepted: September 29, 2016     Published: October 04, 2016


Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4–29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

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