摘要
Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods: 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. Intrathe?cal 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. Diferences were evaluated using a two?tailed test, and P < 0.05 was considered signiicant.Results: 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 beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence 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 rituxi?mab(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.Conclusions: In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo?therapy prophylaxis alone was not suicient 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.
Background： In patients with difuse large B-cell lymphoma（DLBCL）, central nervous system（CNS） relapse is uncom-mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods： 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. Intrathe-cal 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. Diferences were evaluated using a two-tailed test, and P 〈 0.05 was considered signiicant.Results： 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 beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio（HR） = 4.21, 95% conidence 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 rituxi-mab（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.Conclusions： In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemo-therapy prophylaxis alone was not suicient 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.
基金
supported by the National Natural Science Foundation of China(81372883,81001052)
Natural Science Foundation of Guangdong Province,China(2015A030313020 and 8151008901000043)
Science and Technology Planning Project of Guangdong Province,China(2011B031800222)
Young Talents Key Project of Sun Yat?sen University(2015ykzd13,to Qing-qing Cai)
Young Talents Project of Sun Yat-sen University(11ykpy56,to Qing-qing Cai)
the Sister Institution Network Fund of MD Anderson Cancer Center(to Qing-qing Cai and Hui-Rao)
