During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.Key words: H1N1, influenza, pandemic, HSCT. Citation: Ljungman P, de la Camara R, Perez-Bercoff L, Abecasis M, Nieto Campuzano JB, Cannata-Ortiz MJ, Cordonnier C, Einsele H, Gonzalez-Vicent M, Espigado I, Halter J, Martino R, Mohty B, Sucak G, Ullmann AJ, Vázquez L, Ward KN, and Engelhard D for the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT) and the Infectious Complications Subcommittee of the Spanish Group of Haematopoietic Stem-cell Transplantation (GETH).Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients. Haematologica 2011;96(8):1231-1235. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACT Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients Design and MethodsData was collected through two prospective surveys; one from the European Group for Blood and Marrow Transplantation (EBMT) and the other from the Infectious Complications Subcommittee of the Spanish Group of Haematopoietic Stem Cell Transplantation (GETH). All centers belonging to the two organizations were invited to take part. Data were collected from July 2009 through May 2010. While not identical, both surveys collected information through standardized case-collection forms regarding patients' characteristics and their treatment, factors determining their immunosuppressed state, characteristics of the influenza infection, complications, vaccination status, antiviral therapy and outcome. All patients had given their consent to the data collection. Institutional review board approval was sought as required locally at participating centers. Only patients with molecular proof of pandemic influenza A/H1N1 were included. Oseltamivir resistance was assessed when feasible and as clinically indicated by nucleic acid sequencing of the A/H1N1 neuraminidase gene.Lower respiratory tract (LRT) disease was defined as presence of pulmonary infiltrates and...

The outcome of adenovirus (ADV) infections in adult hematopoietic stem cell transplant (HSCT) patients remains poorly characterized. We studied 14 adults and 3 children, who had undergone HSCT and had developed ADV viremia. Peak ADV DNA levels were significantly higher in patients with ADV diseases than in those without (P=0.03). All children survived the ADV infections. Among the 14 adult HSCT patients, 11 were treated with cidofovir, 2 with ribavirin, and 1 did not receive antiviral treatment. Six of the 13 (46%) treated patients developed ADV diseases and 3 of them (23%) died of ADV infections. Sustained viremia (≥3 positive polymerase chain reaction assays during follow-up) was detected in all patients who finally died of ADV infections. However, 2 adults having had transient ADV viremia either survived or died of diseases other than ADV infections. Our study indicates that the outcome of adult HSCT patients with sustained ADV viremia may be poor, even for those who have received anti-ADV treatment.

Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral target epitope-focus profile in serum after HSCT. IgG profiling from four patient groups (donor and/or recipient +/− for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the ‘exclusive recognition analysis (ERA)’ to identify unique CMV epitope responses for each patient group. The ‘exclusive recognition analysis’ of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D−/R−). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV targets elicited also robust cytokine production in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope profiling of entire viral proteomes; this approach can be useful to map relevant targets for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution.

Cytomegalovirus (CMV) reactivation may lead to CMV disease associated with high morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT); the identification of clinically relevant markers may aid in the identification of patients at increased risk for developing CMV-associated complications. We evaluated the phosphorylation of signal transducer and activator of transcription 5 (STAT5) in CD4(+) T cells, CD8(+) T cells, and TCRγδ T cells in response to stimulation with IL-7 or IL-2 after HSCT by analyzing blood samples taken monthly 1 to 6 months after HSCT. Patients were monitored weekly with a quantitative PCR from the time of engraftment for CMV viral load in whole blood until at least day 100 after HSCT. We identified a correlation between clinical outcome regarding CMV replication and the ability to respond to IL-7 and IL-2 defined by STAT5 phosphorylation (pSTAT5). Patients with recurrent or prolonged CMV replications had significantly lower pSTAT5 upon stimulation of T cells with either IL-7 or IL-2 at time points 1 through 3 than those without CMV replication (P < .05). This was also found after stimulation of CD8(+) T cells at time point 2 (P < .05). We conclude that reduced responses to IL-7, reflected by pSTAT5, may represent a clinically relevant functional biomarker for individuals at increased risk for CMV reactivation; our data may also aid in designing better strategies to improve anti-CMV immune responses without increasing the risk of developing graft-versus-host disease.