Ifigeneia Tzannou

A case of acute myelogenous leukaemia characterised by the BCR-FGFR1 translocation.

The 8p11 myeloproliferative syndrome is a rare atypical disorder defined by the presence of rearrangements between the fibroblast growth factor receptor 1 (FGFR1) and 1 of 13 partner genes described to date, including the BCR gene on chromosome 22. The disease characterised by the BCR-FGFR1 fusion gene has distinct biological and clinical features, with significant diversity among the published cases. We report a case of BCR-FGFR1 disease which was presented as acute myeloid leukaemia with an aggressive clinical course and we review all the adult cases published in the literature.

Characterizing the Cellular Immune Response to Parainfluenza Virus 3

Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4+ and CD8+ T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.

Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy

Summary We characterized the cellular immune response to human metapneumovirus (hMPV) and identified a hierarchy of antigen immunodominance. Reactive T-cell expansion in vitro induced T-helper type 1–polarized, polyfunctional virus-specific populations. Detection of hMPV-specific T cells in patients who controlled infections supports the clinical relevance of these cells.

Dynamics of virus-specific T cell immunity in pediatric liver transplant recipients

Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus‐specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus‐specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus‐specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow‐up. Our study illustrates the dynamic changes in virus‐specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.

Primary abdominal muscle lymphoma

Primary skeletal muscle lymphoma accounts for <1% of all lymphomas; a fraction of these arise within the abdominal muscles. Here, we describe the case of an 84-year-old woman who presented with multiple painful abdominal masses that proved to be diffuse large B-cell lymphoma and we discuss the main features of the disease. Clinical differential diagnosis from soft tissue sarcoma can be extremely difficult. Therefore, accurate pathological diagnosis including optimal tissue processing and immunohistochemical staining is vital to ensuring proper treatment.