Prophylactic treatments containing high-dose intravenous methotrexate are better than those consisting of intrathecal methotrexate or no prophylaxis at all in preventing the central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) in intermediate-to-high-risk patients. This is according to a new study by Chinese researchers published in the journal International Immunopharmacology

Intrathecal and high-dose intravenous methotrexate are both recommended as prophylaxis to prevent the central nervous system relapse of DLBCL, Nianhai Zhang, of the Fujian Medical University, in Fuzhou, China, and colleagues reported.

The researchers set out to identify the best prophylaxis strategy. In doing so, they conducted a meta-analysis of the literature to compare the efficacy of the 2 prophylactic approaches and no prophylaxis in intermediate- to high-risk patients with DLBCL.

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The team analyzed 12 studies involving a total of 5950 patients with DLBCL.

The results of the analysis showed that high-dose intravenous methotrexate alone or in addition to intrathecal methotrexate significantly reduces the risk of central nervous system relapse compared to intravenous methotrexate alone. 

Moreover, the efficacy of high-dose intravenous methotrexate was comparable to that of high-dose intravenous methotrexate plus intrathecal methotrexate, which itself was better than intrathecal methotrexate alone. The researchers concluded that intrathecal methotrexate alone is not adequate prophylaxis for the prevention of central nervous system relapse in DLBCL. 

The study team also assessed whether there was a correlation between prophylaxis and survival. Their analysis revealed that the 3-year survival rate of patients not receiving prophylaxis or receiving inadequate prophylaxis, like intrathecal methotrexate, was lower than that of patients receiving high-dose intravenous methotrexate with or without intrathecal methotrexate.

Looking ahead, larger studies are needed to confirm these findings, the authors concluded.


Zhang N, Xu D, Liu B, et al. Prophylaxis strategies containing high dose intravenous methotrexate on preventing CNS relapse for patients with diffuse large B-cell lymphoma at intermediate to high risk: a study based on 12 cohorts in the rituximab era. Int Immunopharmacol. Published online October 17, 2022. doi:10.1016/j.intimp.2022.109299