Possible risk of rheumatoid arthritis treated with methotrexate to the central nervous system relapse of diffuse large B-cell lymphoma.

[PURPOSE] Relapse in the CNS is uncommon but often a fatal event in the patients with diffuse large B-cell lymphoma. An important management strategy consists of identifying patients in the high-risk group for CNS relapse and choosing those who will benefit from CNS prophylaxis. To evaluate rheumatoid arthritis as an additional risk factor for CNS relapse, we retrospectively examined the patients with DLBCL.

[METHODS] We examined 85 patients with diffuse large B-cell lymphoma, admitted to the hospital between June 2016 and May 2021 and followed up for at least three years, and investigate the background of nine patients with CNS relapse. CNS relapse was diagnosed by imaging, clinical, and histological or cytological findings. Also, we evaluated patients with a history of rheumatoid arthritis in these 85 patients. Statistical analysis was performed using Fisher's exact test (Statcel-the Useful Addin Forms on Excel-4th ed.) RESULTS: In the present study, we showed that nine of 85 patients (10.6%) developed CNS relapse. Three of nine cases with CNS relapse had none of the previously reported risks, but received low-dose methotrexate for rheumatoid arthritis. We observed a high proportion of CNS relapse among patients with diffuse large B-cell lymphoma and concomitant rheumatoid arthritis The association between CNS relapse and concomitant rheumatoid arthritis in diffuse large B-cell lymphoma was statistically significant. (CNS relapse / history of RA: +/+ 3, +/- 6, -/+ 5, -/- 71; p = 0.036), using Fisher's exact test.

[CONCLUSIONS] Here we demonstrated a possible risk of rheumatoid arthritis for CNS relapse in diffuse large B-cell lymphoma. High-dose intravenous methotrexate has been increasingly used as a CNS prophylaxis instead of intrathecal methotrexate injection alone in patients with high-risk diffuse large B-cell lymphoma. However, our findings suggest that MTX re-administration in patients with rheumatoid arthritis with diffuse large B-cell lymphoma and high CNS relapse risk warrants particular caution. Clinicians should be aware of the possible risks in these patients, and careful consideration is needed.