Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants.

We have previously shown that hemopoietic stem cell transplant (HSCT) recipients can be stratified on day+7 as having low, intermediate or a high risk of transplant-related mortality (TRM). With the aim of reducing TRM and GVHD, intermediate and high-risk patients (n=170) were randomized to receive anti-thymocyte globulin (ATG, thymoglobuline) on day+7 (n=84) or no treatment (n=86) (controls). There was a reduction of TRM from 35% in controls to 29% in ATG patients (P=0.3), of acute GVHD III-IV from 15 to 5% (P=0.02) and of chronic GVHD from 26 to 11% (P=0.03); survival was comparable. The predictive value of the day+7 score on TRM was confirmed for controls (19 vs 42% for intermediate vs high risk, respectively, P=0.03), whereas ATG abrogated this predictive effect (29 vs 29%). ATG reduced GVHD (P=0.006) in high-risk patients, but not in patients with an intermediate risk. In conclusion, we confirm that TRM can be predicted on the basis of day+7 laboratory values, after alternative donor HSCT; in high-, but not intermediate-risk patients, the administration of ATG on day+7 reduces GVHD. These results may represent a platform for risk-adapted post transplant immune modulation.