Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2 seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

Mogamulizumab-induced interface dermatitis drug rash treated successfully with methotrexate and extracorporeal photopheresis in a patient with Sézary syndrome

“…Steroid-refractory graft-versus-host-disease can be treated with ECP, methotrexate, or a combination of these. 7 , 8 Methotrexate is particularly well suited for both SS and lichenoid reactions, as it is known to suppress dysregulated T cells with toxicity, specifically toward highly proliferative lymphocytes. ECP leads to anti-inflammatory cytokines and stimulation of regulatory T cells, which replenishes regulatory T-cell responses and confers the immunomodulatory effects responsible for counteracting alloimmunity in graft-versus-host-disease and autoimmunity in lichenoid drug reaction.…”

Acute kidney injury after high dose etoposide phosphate: A retrospective study in children receiving an allogeneic hematopoetic stem cell transplantation

“…Several other drugs used in the therapeutic protocol are known to be potentially nephrotoxic, such as ciclosporin, cotrimoxazole, and methotrexate, but no change was made in protocol or clinical practice. Prescriptions were not altered but administered at the same doses in both groups.…”

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

“…Seven patients died of disease progression (nonresponders, four patients; responders, three patients). In a pooled data analysis, the observed overall response was 70% (79/113 patients), with a CR in 59% of patients and a PR in 11% [75]. Pooled data suggested the potential use of methotrexate for SR-aGVHD; however, randomized controlled studies are needed.…”

“…Pooled data suggested the potential use of methotrexate for SR-aGVHD; however, randomized controlled studies are needed. In both studies, methotrexate toxicity was low [74,75].…”