CMV-reaction (CMV-R) after transplant occurs frequently and is generally thought to be associated with a increased TRM. WE aimed to evalute AML in vitro, and further, the clinical outcome of patients with AML with a documented CMV-R after transplant. We retrospectively evaluated 236 pat.with AML in two cohorts (108 pat. in 1st cohort transpl.from an HLA-ident.sibling donor, and 127 pat. transpl. from an HLA-ident.URD. Pat. were transplanted in Essen and Rostock. For the definition of a CMV-R treatment with ganciclovir and the detection of pp65 pos.cells in PMCs at minimum at two different occasions were required. For in vitro studies we used the cell lines Kasumi-1 (AML-M2), SD-1 (ALL) and K562 (CML in blast crises) and infected them with the AD169 CMV strain. 14 days after infection we evaluated the apoptosis rate by measuring annexin V by FACS, the proliferation rate by BRDU assay, the expression of MRD and apoptosis marker p21, c-myc. Infection of CMV in Kasumi-1 cells and SD-1 cells induced in 99.8% and 31.3% of cells apoptosis, whereas no impact on the apoptosis rate was seen for K562 cells. HCMV-induced cell death in AML cells was mediated by a caspase-dependent mechanism and could be prevented by the specific caspase inhibitor zVAD.fmk. These results were in concordance with the clinical observation of a CMV-R after transplant in AML, ALL, and CML. AML-Patients with a documented CMV-R had in both cohorts a markedly reduced risk for relapse (prob. at 5-year 9.2% versus 52.6% in cohort 1 (p<0.0005) and 12.2% versus 47.2% in cohort 2 (p<0.013), which resulted in a sign.improved OS cohort 1 OS 73.6% versus 42.5% (p<0.04) and 48.0% versus 33.5% in cohort 2 (p<0.04). There were no sign. differences in the characteristics of pat. with or without CMV-R. Patients with CMV-R had a higher incidence of acute GVHD grade 2-4 (82% versus 38%, p <0.0001), but this was also seen in pat.with ALL and CML who did not have a reduced risk for relapse after a CMV-R. When stratified according to the occurrence of acute GVHD, the probability for risk of relapse remained sign.lower in pat.with a CMV-R compared to their counterparts (p<0.003). In multivariate analyses the sign.factors impacting the outcome and relapse rate were disease stage, chronic GVHD, unfavorable cytogenetics and CMV-R. Our data indicate an unrecognized role of CMV reactivation after HSCT for AML, which is probably mediated by CMV induced apoptosis.