Non-pharmacologic approaches to graft-versus-host prevention

Allogeneic transplant offers a curative option for selected hematological malignancies and improved disease free survival in those where cure is not possible. For patients in these categories, Graft-versus-host disease (GVHD) occurs often and is a significant cause of morbidity and mortality following transplantation. Pharmacological immunosuppression has considerable toxicity and controls GVHD in about 75% of transplant recipients when used in combination and continually. Thus, there is the need for viable and non-toxic alternatives for GVHD prevention and this is the impetus for seeking novel non-pharmacological strategies. Most techniques directed to this end are based on various permutations of T-cell depletion. Total T-cell depletion was the first graft engineering strategy employed but while beneficial, it was associated with delay in engraftment and early relapses. Modern depletion and adoptive immunotherapy techniques are directed toward specific subsets of T-cells which include alloreactive, naïve, NK cells, T-helper and cytotoxic T-cells. While large bodies of preclinical evidence attest to the efficacy of currently available non-pharmacological prevention techniques, such is not the case with vigorous clinical trials. Where available, the proven non-pharmacological prevention techniques are yet to be fully interwoven into the patient care arena. Integration of available strategies and continuing research are therefore acutely needed to improve the chronic morbidity and mortality seen with both allogeneic transplant-associated GVHD and the use of pharmaceutical immunosuppressants.