Total Body Irradiation without Chemotherapy as Conditioning for an Allogeneic Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia.

Current therapies for acute myeloid leukemia (AML), failing induction, are rarely effective. We report our experience in 4 patients with AML who received 16 Gy TBI prior to allogeneic hematopoietic cell transplantation (alloHCT), between June 2010 and May 2011. Patients were 20 to 55 years of age, 2 with relapsed disease and 2 with AML failing induction.

Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors.

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines.

A high-throughput pharmacoviral approach identifies novel oncolytic virus sensitizers.

Oncolytic viruses (OVs) are promising anticancer agents but like other cancer monotherapies, the genetic heterogeneity of human malignancies can lead to treatment resistance. We used a virus/cell-based assay to screen diverse chemical libraries to identify small molecules that could act in synergy with OVs to destroy tumor cells that resist viral infection. Several molecules were identified that aid in viral oncolysis, enhancing virus replication and spread as much as 1,000-fold in tumor cells.

Allogeneic hematopoietic cell transplantation in human immunodeficiency virus-positive patients with hematologic disorders: a report from the center for international blood and marrow transplant research.

The role of allogeneic hematopoietic cell transplantation (alloHCT) in human immunodeficiency virus (HIV)-positive patients is not known. Using the Center for International Blood and Marrow Transplant Research database, we retrospectively evaluated 23 HIV-positive patients undergoing matched sibling donor (n = 19) or unrelated donor (n = 4) alloHCT between 1987 and 2003. The median age at alloHCT was 32 years.

Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis.

Although recent animal studies have fuelled growing interest in Ab-independent functions of B cells, relatively little is known about how human B cells and their subsets may contribute to the regulation of immune responses in either health or disease. In this study, we first confirm that effector cytokine production by normal human B cells is context dependent and demonstrate that this involves the reciprocal regulation of proinflammatory and anti-inflammatory cytokines. We further report that this cytokine network is dysregulated in patients with the autoimmune disease multiple sclerosis, whose B cells exhibit a decreased average production of the down-regulatory cytokine IL-10.

Carrier cell-based delivery of an oncolytic virus circumvents antiviral immunity.

Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. However, the host immune system remains a significant obstacle to effective systemic administration of virus in a clinical setting. Here, we demonstrate the severe negative impact of the adaptive immune response on the systemic delivery of oncolytic vesicular stomatitis virus (VSV) in an immune-competent murine tumor model, an effect mediated primarily by the neutralization of injected virions by circulating antibodies.

Outpatient autologous hematopoietic stem cell transplantation for patients with relapsed follicular lymphoma.

Autologous stem cell transplantation (ASCT) has emerged as a viable option for the treatment of relapsed follicular non-Hodgkin's lymphoma. We report on the outpatient experience of 60 patients who underwent ASCT for this condition. The median age was 51 years (30-65).