Low-dose MTX for the treatment of acute and chronic graft-versus-host disease in children

Abstract

We report the results of a retrospective analysis in 27 pediatric patients who received low-dose MTX as the second-line treatment for steroid-refractory or -dependent acute and chronic GVHD. Between July 2000 and May 2006, 10 patients with aGVHD and 17 with cGVHD were treated with MTX at a dose of 3-10 mg/m 2 weekly. Seven of ten patients (70%) with aGVHD responded well to MTX, thus resulting in the achievement of either a complete response (CR) or a partial response (PR). The dose of prednisone could be reduced to equal to or lower than 1 mg/kg in the responding patients at the end of MTX therapy. The median number of MTX administrations was five (range, 1-7). Ten (58.8%) of seventeen patients with cGVHD achieved CR or PR. The dose of prednisone could be reduced to lower than 0.4 mg/kg in 16 of 17 patients and seven patients could discontinue prednisone. The median duration of MTX administration was 18 months (range, 1-68). The toxicities of grade III to IV occurred in only six patients presenting cytopenias or elevated levels of serum transaminases. Low-dose MTX was tolerable and effective for the steroid-refractory or -dependent GVHD in reducing the dose of steroid without increasing the risk of opportunistic infection.

State-of-the-art acute and chronic GVHD treatment

“…In a study of 86 patients with cGVHD, a marked benefit in cutaneous disease was observed with low-dose methotrexate as the first-line treatment in combination with other immunosuppressants [150]. Other smaller studies have also shown efficacious results as well [151,152].…”

Optimal management of chronic graft‐versus‐host disease in children

“…While the degree of improvement for PR was not well defined, the authors reported an objective response in 10 (4 CR, 6 PR) of 17 patients, with all but one able to taper prednisone <0AE4 mg/kg/d. Interestingly, 6 of 11 patients with liver involvement had improvement (Inagaki et al, 2008). Infectious toxicity was minimal, making this common agent worthy of further prospective study, especially in patients that are already heavily immunosuppressed.…”

“…Low-dose methotrexate is commonly used for arthritis (van Ede et al, 1998). Inagaki et al (2008) treated 17 paediatric patients with steroid-refractory or dependent chronic GVHD with low dose methotrexate (5-10 mg/m 2 ). Patients received this agent for a median of 18 months; therefore, it appeared to be well-tolerated.…”

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

“…They suggested the effectiveness of rituximab therapy for selected patients with steroid-refractory chronic GVHD that is not advanced. Inagaki et al [131] demonstrated that administration of MTX at a dose of 3-10 mg/m 2 weekly had allowed steroid treatment to be reduced or discontinued in 15 (88 %) of 17 pediatric patients with steroid-refractory or steroiddependent chronic GVHD. Hidaka et al [151] reported the efficacy of bezafibrate for liver chronic GVHD with a poor response to ursodeoxycholic acid.…”

“…Iida et al conducted a nationwide survey to analyze the outcomes of patients who had received MMF as GVHD therapy after related [52] or unrelated [53] donor transplantation. Inagaki et al [131,132] suggested the efficacy of low-dose MTX at a dose of 10 mg/m 2 weekly for pediatric patients in two retrospective studies. They concluded that low-dose MTX therapy has a low risk of opportunistic infection, is low toxicity, is easy to administer, and is inexpensive.…”