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.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved the outcome of patients with DLBCL [1]
Several reports suggest that incorporation of rituximab decreased the rate of central nervous system (CNS) relapse [2, 3], the use of rituximab has failed to decrease the incidence of CNS involvement in patients with an age-adjusted International Prognostic Index (IPI) ≥ 2 [4], and clinical outcomes of those patients are still poor in the rituximab era [5,6,7,8]
Eight patients were excluded because four patients had withdrawn their consent and the other four patients did not meet the inclusion criteria: three patients did not have DLBCL after pathology review, and one patient could not receive R-CHOP due to liver cirrhosis
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved the outcome of patients with DLBCL [1]. Some parameters that reflect the tumor burden, including serum lactate dehydrogenase (LDH) and the number of involved extranodal sites were associated with the risk of CNS relapse in previous studies [2, 10]. German HighGrade Non-Hodgkin Lymphoma Study Group proposed a risk model for the prediction of CNS relapse among patients with DLBCL treated with rituximab-containing immunochemotherapy [13]. They defined five conventional IPI factors in addition to involvement of kidney or adrenal gland as factors for CNS relapse (CNS-IPI). The CNSIPI effectively stratified 2,164 DLBCL patients into 3 risk groups according to the rate of CNS relapse at 2 years. The model was successfully validated among 1,597 patients from the British Columbia Cancer Agency [13]
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