High‑Dose Methotrexate Cuts Brain Lymphoma Relapse and Boosts Survival

A new study looked at whether a special way of giving the drug methotrexate could stop lymphoma from coming back in the brain. The researchers treated 336 patients who had finished a standard chemo plan called RCHOP and were in complete remission. The drug was given as a 3‑hour infusion at a dose of 3 grams per square meter, after an initial quick shot. Which patients got the extra methotrexate was decided by a hospital score that judged their risk of brain relapse. After the study updated the rules, 68 % were low‑risk and 32 % high‑risk. Most of the low‑risk group did not receive the drug, but almost half of the high‑risk patients did.The treatment was safe: 96 % of those who started finished the course. Over a median follow‑up of almost seven years, only 4 % had a brain relapse and those were isolated. In the high‑risk group, patients who received methotrexate had no brain relapses at all, while those who did not get the drug had a 19 % relapse rate. The benefit was especially clear for patients whose lymphoma involved organs that can reach the brain or who had three or more extra‑nodal sites. Survival data matched these findings. In the high‑risk group, overall and progression‑free survival were better when methotrexate was used. The difference seemed to come from fewer brain relapses, not from changes in deaths unrelated to lymphoma or in systemic recurrences. The researchers conclude that using a dose schedule based on drug levels, with or without another brain‑directed chemo method, can meaningfully lower the chance of lymphoma returning in the brain and improve outcomes for high‑risk patients who are otherwise cancer‑free.