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 1, * , Jun Sik Hong 2, * , Myung Hee Chang 3 , Jeong-A Kim 4 , Jae-Yong Kwak 5 , Jin Seok Kim 6 , Dok Hyun Yoon 7 , Won Sik Lee 8 , Young Rok Do 9 , Hye Jin Kang 10 , Hyeon-Seok Eom 11 , Yong Park 12 , Jong-Ho Won 13 , Yeung-Chul Mun 14 , Hyo Jung Kim 15 , Jung Hye Kwon 16 , Jee Hyun Kong 17 , Sung Yong Oh 18 , Sunah Lee 19 , Sung Hwa Bae 20 , Deok-Hwan Yang 21 , Hyun Jung Jun 22 , Yang Soo Kim 23 , Hwan Jung Yun 24 , Soon Il Lee 25 , Min Kyoung Kim 26 , Eun Kyung Park 27 , Won Seog Kim 1 , Cheolwon Suh 7 1 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea 3 Department of Hematology-Oncology, National Health Insurance Service Ilsan Hospital, Goyang, Gyeongki-do, Korea 4 Department of Internal Medicine, St. Vincent's Hospital, the Catholic University of Korea, Seoul, Korea 5 Department of Internal Medicine, Chonbuk National University Medical School & Hospital, Jeonju, South Korea 6 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea 7 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 8 Department of Internal Medicine, Inje University College of Medicine, Inje University Busan Paik Hospital, Gaegumdong, Busanjingu, Busan, Republic of Korea. 9 Division of Hematology-Oncology, Department of Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea 10 Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea 11 Hematology-Oncology Clinic, National Cancer Center, Goyang-city, Korea 12 Department of Internal Medicine, Korea University Anam Hospital, College of Medicine, Seoul, Korea 13 Department of Internal Medicine, Soon Chun Hyang University, Seoul, Korea 14 Department of Internal Medicine, Ewha Womans University, Seoul, Korea 15 Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Chucheon, Korea 16 Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea 17 Division of Hematology-Oncology, Department of Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Korea 18 Department of Internal Medicine, Dong-A University Hospital, Busan, Korea 19 Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea 20 Department of Internal Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea 21 Department of Hemato-oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Korea 22 Department of Internal Medicine, Seoul Medical Center, Seoul, Korea 23 Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea 24 Department of Hemato-oncology, Chungnam National University Hospital, Daejeon, Korea 25 Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea 26 Department of Medicine, Yeungnam University College of Medicine, Daegu, Korea 27 Department 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: wskimsmc@skku.edu Cheolwon Suh, email: csuh@amc.seoul.kr Keywords: diffuse large B-cell lymphoma, central nervous system, prognosis, lactate dehydrogenase Received: August 11, 2016 Accepted: September 29, 2016 Published: October 04, 2016 ABSTRACT 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.