Graft‐versus‐host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: long‐term follow‐up of a controlled trial

Abstract

Forty-six patients with aplastic anaemia (median age 23 years) were given cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-versus-host disease (GVHD), the patients were entered into a randomized prospective trial comparing a combination of methotrexate and cyclosporin (n = 22) to methotrexate alone (n = 24). Methotrexate/cyclosporin significantly reduced the incidence and severity of acute GVHD and improved early survival. This report updates the results of the randomized trial with followup ranging from 3 to more than 6 years. The methotrexate/cyclosporin regimen did not interfere with sustained engraftment, and there were no significant differences in the incidence of early or late graft rejection among the two treatment groups (10% v 4%). The incidence of chronic GVHD was higher among methotrexate/cyclosporin-treated patients (58% v 36%; P = 0.18). Two patients in each treatment group still require treatment for chronic GVHD, while treatment is no longer needed in the other patients. Projected 4-year survival is 73% in patients given methotrexate/cyclosporin compared to 58% in patients given methotrexate alone (P = 0.16). Having achieved a reduction in the incidence of acute GVHD and associated early mortality without impairing engraftment, it is clear that future progress in marrow grafting for aplastic anaemia must come in the area of chronic GVHD.

Tacrolimus instead of cyclosporine used for prophylaxis against graft-versus-host disease improves outcome after hematopoietic stem cell transplantation from unrelated donors, but not from HLA-identical sibling donors: a nationwide survey conducted in Japan

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Cyclosporine (CSP) is the most commonly used agent, and the combination of CSP and short-term methotrexate (MTX) has been adopted as standard treatment. [1][2][3][4][5][6] Tacrolimus (FK506) has a similar mechanism of action as CSP, and also inhibits T-cell activation by blocking the phosphatase activity of calcineurin. 15,16 This drug was introduced into clinical studies for GVHD prophylaxis in the mid 1990s.…”

Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach

“…Pediatric patients received cyclosporine and 'short course' methotrexate. [12][13][14] Endoscopic protocol All endoscopies were performed or supervised by one of the authors (CW) using Olympus (Lake Success, NY, USA) endoscopes. Ileal intubation was attempted at the time of colonoscopy in all patients.…”

Graft-versus-host disease following marrow transplantation for aplastic anemia: different impact of two GVHD prevention strategies

“…Randomized studies in patients with AA have shown that the combination of CsA and MTX is superior to either agent alone for prevention of GVHD. [1][2][3] At present, CsA and MTX is the most commonly used GVHD prophylaxis regimen for AA. In addition to CsA and MTX, some centers use antithymocyte globulin (ATG) in conditioning protocols for AA.…”