Mini-dose methotrexate may be an effective prophylaxis strategy against graft-versus-host disease (GVHD) among patients with hematologic malignancies undergoing allogenic hematopoietic stem-cell transplantation (HSCT). These results, from a retrospective analysis, were published in the Journal of Hematology Oncology Pharmacy.

Although methotrexate is commonly used as GVHD prophylaxis after HSCT, it is associated with oral mucositis, nephrotoxicity, and hepatotoxicity. In this study, researchers sought to determine the usefulness of a folinic acid rescue protocol as a preventive strategy for methotrexate-induced oral mucositis, based on this facility’s experience with mini-dose methotrexate prophylaxis after HSCT (5 mg/m2 on days 1, 3, 6, and 11 with tacrolimus 0.03 mg/kg daily continuous infusion every 24 hours, starting on day 1).

Patients (N=48) who underwent HSCT at Mount Sinai Hospital in New York, New York, between July 2013 and June 2015 were assessed for GVHD and clinical outcomes.

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Patients were aged mean 53 years (interquartile range [IQR], 43.3-63.3) and 62.5% were women.

Following HSCT, oral mucositis was reported by 17 patients (grade 1 or 2: 22.9%; grade 3 or 4: 12.5%) beginning on day 2 and ending on day 16.

Patients received methotrexate on days 1 (95.8%), 3 (100%), 6 (97.9%), and 11 (95.8%). Oral opioids were required by 50% for a mean of 7.5 days (IQR, 3-15.3), total parenteral nutrition by 29.2% for 18.5 days (IQR, 6.3-37.8), and patient-controlled analgesics by 16.7% for 19 days (IQR, 5.8-33.5).

Time to neutrophil engraftment was not associated with oral mucositis (P =.76) nor was time to oral mucositis associated with methotrexate doses (P =.93).

Relapse by day 30 occurred in 12.5%, and renal and hepatic functioning did not differ from baseline. Survival by day 100 was 85.4%.

This study was biased by not including a comparator group to assess safety of methotrexate nor did it include assessment of folinic acid rescue, which may have reduced oral mucositis incidence.

These results suggested mini-dose methotrexate may be an effective prophylaxis for patients undergoing HSCT to reduce rates of GVHD. The authors speculated that incorporating folinic acid rescue may decrease incidence of oral mucositis in patients at highest risk for grade 3 or 4, warranting further study.


Solodokin L J, Steinberg A, Moshier E. The safety profile of mini-dose methotrexate for graft-versus-host disease prophylaxis: is there a place for folinic acid rescue? J Hematol Oncol Pharm. 2020;10(6):346-353.