Interpretation of retrospective data evaluating high?dose methotrexate as central nervous system prophylaxis in diffuse large B?cell lymphoma; caution required

To the Editor: There remains a lack of consensus regarding efficacy high-dose methotrexate (HD-MTX) prophylaxis to reduce risk central nervous system (CNS) relapse in newly diagnosed patients with systemic diffuse large B-cell lymphoma (DLBCL). The clinical controversy reflects high-quality evidence supporting optimal strategies, coupled poor outcomes who experience CNS relapse. Interest this area has been rejuvenated recently following publication number retrospective studies1-6 investigating critical question. We commend Puckrin and colleagues7 for attempting address role HD-MTX evaluation their regional practice. Although authors acknowledge many limitations associated study nature, we feel that results presented by et al. merit more nuanced balanced discussion. This is particularly important when interpreting significance rare events, context an uncontrolled modest-sized dataset exposed biases. Evaluating effectiveness strategies DLCBL priority and, given randomized trial data may never be forthcoming, are reliant on analyses contribute generate hypotheses difficult area. However, it clear studies adopt appropriate caution generated. Based al., believe simply not possible draw conclusions or otherwise as prophylaxis. statement included title manuscript cannot robustly defended presented. other similar analyses,2, 4-6 highlight urgent need much larger, adequately powered, international collaborative uniformly treated at high order confidently declare no conflict interest. Data sharing applicable article new were created analyzed study.