Omitting the Day 11 Administration in Mini-Dose Methotrexate

By Patrick Daly - Last Updated: November 16, 2022

Following allogeneic hematopoietic cell transplantation (HCT), conventional graft-versus-host disease (GVHD) prophylaxis with calcineurin inhibitors and methotrexate is sometimes replaced by methotrexate 5 mg/m2 on day 1, 3, 6, and 11 in patients where toxicity is a concern. Researchers evaluated the effects of omitting the day 11 administration. They found that omitting the dose lowered the risk of mucosal damage and bacterial infection, but it increased the risk of severe acute and chronic GVHD.

Day 11 Methotrexate Necessary in GVHD Prevention

The study, published in Transplantation and Cellular Therapy, investigated 135 retrospective cases of unrelated bone marrow transplantation at the authors’ center from 2006 to 2019. In total, 72 patients who did not receive the day 11 dose were compared with 63 patients who did receive it.

Researchers reported the 4-year overall survival (OS) was 58.7%. The day-11-omitted group had worse GVHD-free, relapse-free survival (P=.01) with comparable OS (P=.11) and relapse-free survival (P=.11).

In addition, the authors noted human leukocyte antigen mismatch between donor and recipient was a major risk factor for severe GVHD. Analyses of matched or mismatched subgroups found patients without the day 11 dose of methotrexate had higher risks for severe acute and chronic GVHD.

“The omission of day 11 [methotrexate] was associated with a higher risk of severe GVHD. Therefore, the omission of the day 11 dose is not recommended,” the authors concluded.