Survivors after blood wars.

survival such as GVHD and leukemia risk group. Elmaagacli and colleagues propose several explanations for these results (see figure). First, myeloid cells are a reservoir for CMV. It is possible that viral reactivation in AML blasts makes them a target for subsequent attack by virus-specific cytotoxic T cells (CTLs). Alternatively, CMV reactivation in AML cells may up-regulate leukocyte fixation antigen-3 (LFA-3) expression and enhance natural killer (NK)– cell cytotoxicity against the leukemia. 6 Last, the virus could have a direct cytotoxic effect on the AML cell: a virus-versus-leukemia effect. Of these possibilities the idea that CMV renders the leukemia a target for immune attack seems the more likely. CMV reactivation is a trigger for expansion of potent CTLs targeting the virus, 7 and while antivirals are routinely used to suppress viremia it is clear from the observation that antigenemia falls as CMV-specific T-cell frequencies rise and the effectiveness of virus-specific T-cell therapy that the immune response is central to controlling the virus. There is some evidence that AML is especially susceptible to alloge-neic effects of NK cells after SCT, and an NK-targeting of CMV-infected AML blasts is also conceivable. These hypotheses are test-able: we can explore the relationship between the rise of CMV-reactive CTL and AML relapse , which should correlate even better with relapse control than pp65 antigenemia. In vitro studies of the interaction of NK cells and CMV-specific CTLs with AML cells infected with CMV are indicated. First, however, this article challenges us to review our own databases to determine whether they validate these remarkable and significant findings. Conflict-of-interest disclosure: The author declares no competing financial interests. ■ REFERENCES 1. Elmaagacli AH, Steckel NK, Koldehoff M, et al. Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a puta-tive virus-versus-leukemia effect in acute myeloid leukemia patients. 3. Winston DJ, Gale RP. Prevention and treatment of cy-tomegalovirus infection and disease after bone marrow transplantation in the 1990s. posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus an-tigen and predicts for increased late relapse and treatment failure. cell lysis of cytomegalovirus (CMV)-infected cells correlates with virally induced changes in cell surface lymphocyte function-associated antigen-3 (LFA-3) expression and not with the CMV-induced down-regulation of cell surface class I HLA. reconstituted adaptive and innate cytomegalovirus (CMV)-specific immune responses with CMV viremia in hemato-poietic stem cell transplant recipients. As more transplants are performed yearly and outcomes …