Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT.

Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004-August 2008), predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n=60) or non-myeloablative (NMA; n=48) conditioning regimen were included. Median age was 40 years (range 17-65); median follow-up was 20 months (range 3-36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50 323 cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100 cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P=0.02). In addition, HHV6 reactivation was associated with grades 2-4 aGVHD (P<0.001) and NRM (P=0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome.

Stem cell source-dependent reconstitution of FOXP3+ T cells after pediatric SCT and the association with allo-reactive disease.

In adult patients, regulatory CD4+FOXP3+ T cells are suggested to have a role in the control of allo-reactive disease after hematopoietic SCT (HSCT). We compared CD4+FOXP3+ T-cell reconstitution after unrelated cord blood (UCB), matched unrelated donor (MUD) and matched sibling donor (MSD) HSCT in children, starting as early as 1 week after transplantation, and analyzed the association with allo-reactive disease. A total of 30 children were included who underwent a myeloablative-conditioning regimen followed by UCB (12/30), MUD (7/30) or MSD (11/30) HSCT. These three patient groups showed significant differences in FOXP3+ T-cell reconstitution pattern. Early after UCB and MSD, but not after MUD, HSCT a peak in FOXP3+ T cells was observed. There were significant differences in activation status and Ki67 expression of the FOXP3+ T cells after UCB and MSD, respectively. FOXP3+ T-cell proportions early after HSCT and in the graft were inversely correlated with allo-reactivity. This study indicates that FOXP3 reconstitution after HSCT is dependent on the type of graft used. Furthermore, in children evaluation of FOXP3+ T-cell numbers early after HSCT and in the graft may be used to judge the risk of developing allo-reactivity after HSCT.