Should methotrexate plus calcineurin inhibitors be considered standard of care for prophylaxis of acute graft-versus-host disease?

Abstract

In a rapidly developing field, one can always anticipate that different interpretations of similar data will coexist. Stem cell transplanters can be a contentious lot, especially in the absence of controlled randomized trials. Thus, although improvements in the basic understanding of acute graft-versus-host disease (aGVHD) has led to many testable hypotheses in the management of GVHD, there remains little consensus regarding the most effective and least toxic approach to GVHD prevention. In the 1980s, the comparison would have been between cyclosporine-based regimens and ex vivo T cell depletion (TCD). Although ex vivo TCD is still used in some settings, pharmacologic-based therapy and in vivo TCD with serotherapy now predominate. This review is meant to highlight the advantages and disadvantages of the "standard of care" and assess the prospects for future regimens that may be more effective.

Figure 1

Survival and chronic GVHD in patients with aplastic anemia (2–63 years old) given HLA-matched related grafts and receiving MTX/CSP after conditioning with cyclophosphamide and anti-thymocyte globulin (Cy/ATG). Similar results have been reported in children by Locatelli et al..

Figure 2

Survival of patients with chronic myelogenous leukemia in chronic phase (CML-CP) given HLA-matched unrelated HCT and receiving MTX/CSP after conditioning with cyclophosphamide and total body irradiation (Cy/TBI). This represents a subgroup of patients who received prophylaxis with fluconazole and ganciclovir.