ABSTRACT
Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that human herpesvirus-6B (HHV-6B) plays a role in acute GVHD (aGVHD) after HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. PubMed and EMBASE databases were searched using terms for HHV-6, HCT, and aGVHD, yielding 865 unique results. Case reports, reviews, articles focusing on inherited chromosomally integrated HHV-6, poster presentations, and articles not published in English were excluded. The remaining 467 articles were reviewed for the following requirements: a statistical analysis of HHV-6B reactivation and aGVHD was described, HHV-6B reactivation was defined by PCR, and blood (plasma, serum, or peripheral blood mononuclear cells) was used for HHV-6B PCR. Data were abstracted from publications that met these criteria (n = 33). Publications were assigned to 1 of 3 groups: (1) HHV-6B reactivation was analyzed as a time-dependent risk factor for subsequent aGVHD (n = 14), (2) aGVHD was analyzed as a time-dependent risk factor for subsequent HHV-6B reactivation (n = 1), and (3) analysis without temporal specification (n = 18). A statistically significant association (P < .05) between HHV-6B reactivation and aGVHD was observed in 10 of 14 studies (71%) in group 1, 0 of 1 study (0%) in Group 2, and 8 of 18 studies (44.4%) in Group 3. Of the 14 studies that analyzed HHV-6B as a risk factor for subsequent aGVHD, 11 performed a multivariate analysis and reported a hazard ratio, which reached statistical significance in 9 of these studies. Meta-analysis of these 11 studies demonstrated a statistically significant association between HHV-6B and subsequent grades II to IV aGVHD (hazard ratio, 2.65; 95% confidence interval, 1.89 to 3.72; P < .001). HHV-6B reactivation is associated with aGVHD, and when studies have a temporal component to their design, HHV-6B reactivation is associated with subsequent aGVHD. Further research is needed to investigate whether antiviral prophylaxis reduces incidence or severity of aGVHD.
Subject(s)
Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Herpesvirus 6, Human/pathogenicity , Transplantation Conditioning/methods , Acute Disease , Adolescent , Adult , Aged , Female , Graft vs Host Disease/pathology , Humans , Male , Middle Aged , Neoplasm Grading , Risk Factors , Young AdultABSTRACT
Transplantation of 1 or 2 umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in each infusion results in slow engraftment. In mouse models, administration of parathyroid hormone (PTH) is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced-intensity double umbilical cord blood transplantation, followed by PTH at 100 µg/day for 28 days. Thirteen patients (median age, 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment of >20 × 10(9) cells/L was 30 days and 61 days, respectively. The incidence of grade II-IV acute GVHD was 38.5% at day 100. Four deaths occurred before day 100, prompting early study closure. No patient who received a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62%, and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery.
