Key messages
toxicity, sepsis, death, mucositis
SEPSIS, MUCOSITIS

What is already known about this area?We searched the PUBMED using the terms "Methotrexate"[Mesh] AND “toxicity” and could not find any randomized controlled study which compared different doses of leucovorin in low-dose methotrexate toxicity. Leucovorin is generally used at a dose of 10 to 25 mg every 6hourly (varies by center) in low-dose methotrexate toxicity – extrapolated from regimens followed for high-dose MTX rescue.What new does this study add? First RCT to compare two different doses of leucovorin in severe-low dose methotrexate toxicityThere was no significant difference in mortality or time-to-hematologic recovery or mucositis recovery between the doses of 15 or 25 mg every 6-h in low-dose methotrexate toxicity. There was substantial mortality in both groups ranging from 42-47% despite leucovorin, with the common cause of death being sepsis. How might this impact clinical practice or future development?Higher doses of leucovorin than 15 mg every 6 h unlikely to help to improve mortality, rather better critical care may help. Unclear whether lower doses may be as beneficial.Need to emphasize preventive aspect of MTX toxicity– physicians should emphasize the unique dosing of MTX to patients and give a warning against daily use at the time of consultation.