New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma: a retrospective study.
In patients with diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) relapse is uncommon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the efficacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.



A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat-sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathecal chemotherapy prophylaxis (methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R-CHOP set in particular, the Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Differences were evaluated using a two-tailed test, and P < 0.05 was considered significant.



At a median follow-up of 46 months, 25 (4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3-year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R-CHOP group (P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much benefit in terms of preventing CNS relapse. Bone involvement [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.38-12.77], renal involvement (HR = 3.85, 95% CI 1.05-14.19), alkaline phosphatase (ALP) >110 U/L (HR = 3.59, 95% CI 1.25-10.34), serum albumin (ALB) <35 g/L (HR = 3.63, 95% CI 1.25-10.51), treatment with rituximab (HR = 0.34, 95% CI 0.12-0.96), and a time to complete remission ≤ 108 days (HR = 0.22, 95% CI 0.06-0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement (HR = 4.44, 95% CI 1.08-18.35), bone marrow involvement (HR = 11.70, 95% CI 2.24-60.99), and renal involvement (HR = 10.83, 95% CI 2.27-51.65) were independent risk factors for CNS relapse in the R-CHOP set.



In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemotherapy prophylaxis alone was not sufficient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R-CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. caiqq@sysucc.org.cn.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China. caiqq@sysucc.org.cn.
Qing-Qing
QQ
Cai
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
Li-Yang
LY
Hu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Hematology Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
Qi-Rong
QR
Geng
Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, Guangdong, P. R. China.|Department of Radiotherapy, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, Guangdong, P. R. China.
Jie
J
Chen
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Colorectal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
Zhen-Hai
ZH
Lu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
Hui-Lan
HL
Rao
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
Qing
Q
Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
Wen-Qi
WQ
Jiang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
Hui-Qiang
HQ
Huang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
Tong-Yu
TY
Lin
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.|Department of Hematology Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
Zhong-Jun
ZJ
Xia
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology*; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
Central nervous system relapse; Diffuse large B-cell lymphoma; Intrathecal chemotherapy prophylaxis; Risk factor; Rituximab