Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation.

Immune reconstitution after allogeneic stem cell transplantation is a dynamic and complex process depending on the recipient and donor characteristics, on the modalities of transplantation, and on the occurrence of graft-versus-host disease. Multivariate methods widely used for gene expression profiling can simultaneously analyze the patterns of a great number of biological variables on a heterogeneous set of patients. Here we use these methods on flow cytometry assessment of up to 25 lymphocyte populations to analyze the global pattern of long-term immune reconstitution after transplantation. Immune patterns were most distinct from healthy controls at six months, and had not yet fully recovered as long as two years after transplant. The two principal determinants of variability were linked to the balance of B and CD8(+) T cells and of natural killer and B cells, respectively. Recipient's cytomegalovirus serostatus, cytomegalovirus replication, and chronic graft-versus-host disease were the main factors shaping the immune pattern one year after transplant. We identified a complex signature of under- and over-representation of immune populations dictated by recipient's cytomegalovirus seropositivity. Finally, we identified dimensions of variance in immune patterns as significant predictors of long-term non-relapse mortality, independently of chronic graft-versus-host disease.

Clinical severity scores in gastrointestinal graft-versus-host disease.

BACKGROUND: The clinical prognosis of gastrointestinal (GI) graft-versus-host disease (GvHD) is based on either a clinical staging system or histological or endoscopic findings. How these different scores correlate with each other and which have the greater impact on transplantation outcomes is, however, not clear. METHODS: Clinical, pathological, and endoscopic findings of the upper GI tract on 201 patients who underwent allogeneic hematopoietic stem cell transplantation were reviewed. The association between clinical, histological, and endoscopy grading was assessed by Kendall correlation coefficient. The agreement between grading systems was evaluated by kappa statistics. Factors associated with survival or steroid resistance were analyzed by proportional hazard models. RESULTS: At disease onset, no strong association was found between pathological and clinical grade at disease onset (τ=0.034, P=0.6). In contrast, endoscopy score and clinical grades were strongly associated (τ=0.37, P<0.001). The Kappa concordance coefficient (0.20) between histological and endoscopy scores was poor. However, by multivariate analysis all three scores significantly predicted survival rates CONCLUSIONS: Clinical, histological, and endoscopic scores poorly correlated with each other when estimated at the GI-GvHD onset. However, all three severe initial scores independently predict poor outcome. Of interest, clinical and endoscopic scores predict resistance to steroids while pathological does not.