title: 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.
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.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Hong
authors.affiliation: Department of Hematology-Oncology, National Health Insurance Service Ilsan Hospital, Goyang, Gyeongki-do, Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, St. Vincent's Hospital, the Catholic University of Korea, Seoul, Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School & Hospital, Jeonju, South Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Inje University College of Medicine, Inje University Busan Paik Hospital, Gaegumdong, Busanjingu, Busan, Republic of Korea.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Do
authors.affiliation: Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Hematology-Oncology Clinic, National Cancer Center, Goyang-city, Korea.
authors.forename: Hyeon-Seok
authors.initials: HS
authors.lastname: Eom
authors.affiliation: Department of Internal Medicine, Korea University Anam Hospital, College of Medicine, Seoul, Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Soon Chun Hyang University, Seoul, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Won
authors.affiliation: Department of Internal Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Yeung-Chul
authors.initials: YC
authors.lastname: Mun
authors.affiliation: Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Chucheon, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea.
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Wonju Severance Christian Hospital, Yonsei University College of Medicine, Wonju, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kong
authors.affiliation: Department of Internal Medicine, Dong-A University Hospital, Busan, Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea.
authors.forename: Sunah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea.
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Hemato-oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Seoul Medical Center, Seoul, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Jun
authors.affiliation: Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea.
authors.forename: Yang Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Hemato-oncology, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Hwan Jung
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
authors.forename: Soon Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Medicine, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chung Ang University, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Park
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D045022:Lactate Dehydrogenases / Q000097:blood*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use; D012698:Serologic Tests / Q000379:methods; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D045022:Lactate Dehydrogenases; D011241:Prednisone
keywords: central nervous system; diffuse large B-cell lymphoma; lactate dehydrogenase; prognosis