A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma

BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP ‘group 1' R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX ‘group 2' dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX ‘group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1–3, respectively). With median follow-up of 3.4 (range 0.2–18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1–3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5–33.1%), 6.9% (3.5–13.4%) and 2.3% (0.4–15.4%) in groups 1–3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.