Low-dose MTX combined with low-dose methylprednisolone as a first-line therapy for the treatment of acute GVHD: safety and feasibility

Abstract

To study the efficacy and safety of a low dose of MTX combined with a low dose of methylprednisolone (MP) as a first-line therapy in the treatment of acute GVHD (aGVHD) after allogeneic hematopoietic SCT, 32 patients received i.v. MTX at a dose of 10 mg or oral MTX at a dose of 15 mg every 3-7 days (repeated at day 3 after the first dose and then at a weekly interval) combined with a low dose of MP (0.5 mg/kg/day) until a complete or partial response was achieved, or until treatment failure or intolerable side effects occurred. The overall treatment response rate was 81% (26/32 patients) and the response rate at day 28 was 75% (24/32 patients). The response rate for GVHD involving various organs was 88% (23/26) in the skin, 75% (3/4) in the liver and 81% (9/11) in the gut. Grade 3 toxicities occurred in only three patients presenting cytopenias. The estimated survival at 2 years was 77%. From this analysis, MTX in combination with a low dose of MP appears to be a well-tolerated, effective and inexpensive regime when used as a first-line treatment for aGVHD.

Prevention of relapse using granulocyte CSF-primed PBPCs following HLA-mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: a retrospective risk-factor analysis

“…Other therapeutic options for acute or chronic GVHD are mycophenolate mofetil, tacrolimus (FK506), azathioprine, thalidomide, monoclonal antibodies directed against CD3 and CD25, and MTX. 10 Definitions and assessments Advanced-stage acute leukemia was defined in the 'Patient eligibility' section of the Materials and methods. Neutrophil engraftment was defined as an ANC of 0.5 Â 10 9 /L or more for 3 consecutive days and platelet engraftment was defined as 20 Â 10 9 /L or more for 7 consecutive days without transfusions.…”

Have we improved in preventing and treating acute graft-versus-host disease?

“…Additional glucocorticoid-sparing strategies have tested low dose MTX combined with low dose methylprednisolone (0.5 mg/Kg/day followed by taper on day 5 and cessation at about day 30) for the treatment of acute GVHD with encouraging results. 36 In summary, these studies established the proof of principle that steroids-sparing approaches are feasible and should be further explored to reduce morbidity and improve OS after HCT.…”

Modified Busulfan and Cyclophosphamide Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Patients With Hematologic Malignancies

“…The majority of patients with recurrent or continuous aGVHD are found to be at a higher risk of death and greater steroid exposure as well [22,23]. Moreover, the increased risk of death is identified to be 2% for every 1.0 mg/kg increase in cumulative MP exposure [7]. In previous studies, the feasibility of low-dose MTX in the treatment of aGVHD has been assessed, mostly as a salvage therapy [24,25].…”

“…The incidences of VOD, aGVHD, and HC are lower than that of traditional BU/CY conditioning regimen [18,19]. It is reported that VOD is associated with BU exposure which is thought to be disease-specific.…”