Isavuconazole treatment of a patient with disseminated mucormycosis.

We report a patient with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated mucormycosis due to Rhizomucor pusillus/R. miehei involving lung, brain, and skin. After failing posaconazole and being intolerant to amphotericin, he was treated effectively with isavuconazole for over 6 months despite ongoing treatment for relapsed leukemia.

Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial.

BACKGROUND: Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important. METHODS: We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28. Twenty-four hematopoietic stem cell transplant recipients were enrolled sequentially into the study, and vaccine or placebo was administered under a randomized, double-blind allocation. Ten subjects received vaccine containing 10(7) median tissue culture infective doses (TCID50) of MVA-BN, 10 subjects received vaccine containing 10(8) TCID50 of MVA-BN, and 4 subjects received placebo. RESULTS: MVA-BN was generally well tolerated at both doses. No vaccine-related serious adverse events were identified. Transient local reactogenicity was more frequently seen at the higher dose. Neutralizing antibodies (NAb) to Vaccinia virus (VACV) were elicited by both doses of MVA-BN and were greater for the higher dose. Median peak anti-VACV NAb titers were 1:49 in the lower-dose group and 1:118 in the higher-dose group. T-cell immune responses to VACV were detected by an interferon γ enzyme-linked immunosorbent spot assay and were higher in the higher-dose group. CONCLUSIONS: MVA-BN is safe, well tolerated, and immunogenic in HSCT recipients. These data support the use of 10(8) TCID50 of MVA-BN in this population. CLINICAL TRIALS REGISTRATION: NCT00565929.

Respiratory virus detection in immunocompromised patients with FilmArray respiratory panel compared to conventional methods.

Respiratory virus infections cause significant morbidity and mortality in immunocompromised patients. Timely diagnosis is needed to provide optimal clinical care. Diagnostic tests routinely available at most institutions are limited by poor sensitivity and a slow turnaround time. We collected 90 respiratory samples from 87 immunocompromised patients (56 bronchoalveolar lavage and 34 nasopharyngeal aspirate samples) in order to compare the performance of routine respiratory virus testing available at our institution to the FilmArray respiratory panel assay, a novel diagnostic tool which utilizes multiplex PCR to test for 21 respiratory pathogens with a 1-h turnaround time. Samples with discordant results and 13 samples with concordant results underwent further verification testing by laboratory-developed real-time PCR. The FilmArray assay identified viral pathogens in more samples than did clinical testing (30/90 versus 16/90; McNemar P = 0.001). Most of the additional viral pathogens identified by the FilmArray respiratory panel assay that were confirmed by verification testing were pathogens not assessed by routine clinical tests, including rhinovirus/enterovirus, human metapneumovirus, and coronavirus. The FilmArray respiratory panel assay allowed for increased identification of respiratory viral pathogens in this cohort of immunocompromised patients.

Seroprotective titers against 2009 H1N1 influenza A virus after vaccination in allogeneic hematopoietic stem cell transplantation recipients.

Little data are available regarding the safety and immunologic response to pandemic H1N1 influenza vaccine in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). We measured serum antibody titers against A/California/7/2009 H1N1 using a hemagglutination inhibition assay in 82 allogeneic HSCT recipients who received the 2009 H1N1 vaccine between November 2009 and January 2010 after it became available at our institution. The median time between HSCT and vaccination was 19 months (range, 2.5-94 months), and the median time from vaccination to specimen collection was 56 days (range, 14-140 days). Seroprotective antibody titers (hemagglutination inhibition titer ≥1:40) against 2009 H1N1 influenza A virus were detected in 51% of patients. The presence of chronic graft-versus-host disease and type of conditioning regimen did not affect the rate of detection of seroprotective titers after vaccination. Patients were more likely to have a seroprotective titer the farther away from HSCT they were (adjusted odds ratio, 1.79 per year; 95% confidence interval, 1.12-2.85). Rituximab administration in the year before vaccination was associated with a lack of seroprotective titer (adjusted odds ratio, 0.11; 95% confidence interval, 0.01-0.97). The vaccine was safe and well tolerated. Strategies are needed to improve the influenza vaccine response in this population, especially those receiving immunotherapy.