An effective acute graft‐vs.‐host disease prophylaxis with minidose methotrexate, cyclosporine, and single‐dose methylprednisolone

Abstract

Cyclosporine and methotrexate at standard doses (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11, total 45 mg/m2) are effective in the prophylaxis of acute graft-vs.-host disease. However, the combination has significant early toxicities with delayed engraftment, increased mucositis, and hepatotoxicity. We modified the combination by adding single-dose methylprednisolone and lowered the total dose of methotrexate to 35 mg/m2 (5 mg/m2 on days 1, 3, and 6, and then 10 mg/m2 on days 11 and 18) and then to 20 mg/m2 (5 mg/m2 on days 1, 3, 6, and 11) in an attempt to decrease these side effects in two sequential consecutive groups of patients. We demonstrated that the modified regimens maintained the efficacy with reduced toxicities. The rate of engraftment was comparable to cyclosporine alone and the hepatotoxicity was reduced with reduced doses of methotrexate. Factors such as early immunosuppression of the host, intravenous immunoglobulin, the timing of steroid administration, nucleotide free diet and germ free environment may contribute to the effectiveness of the combination and permit reduction of methotrexate dose.

A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation

“…This reduced dosage has been used at our institution, and others, for years, specifically designed to reduce the incidence and severity of mucositis associated with MTX. [31][32][33] However, confirming the results of this trial in patients treated with a more common MTX dosing regimen would be beneficial. Another potential problem with this trial is the fact that we used mucositis as a primary end point that resulted in premature study closure.…”

Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA‐identical sibling donor allogeneic hematopoietic cell transplantation

“…The reduced dose schema of 5 mg/m 2 days 1, 3, 6, and 11 was originally developed at the M.D. Anderson Cancer Center [33] specifically to decrease the risk of mucosal and hepatic complications, and has been widely used and shown to be effective in combination with CSA or tacrolimus as GVHD prophylaxis with historically similar outcomes as standard doses [33][34][35][36]. Reduced doses of MTX, however, have not been directly compared to standard doses of MTX.…”

Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation

“…In addition, a reduced dosage scheme of 5 mg/m 2 on days 1, 3, 6, and 11 is frequently used with the aim of decreasing the risk of mucosal and hepatic complications. This regimen has proven effective in combination with CSA or Tac as GVHD prophylaxis, with historically similar outcomes as seen with standard dosing [36][37][38][39]. However, these reduced doses of MTX have never been directly compared with standard dosing of MTX, and thus never been proven to be equivalent, but would have been included in this analysis.…”