Romidepsin and lenalidomide-based regimens have efficacy in relapsed/refractory lymphoma: Combined analysis of two phase I studies with expansion cohorts.

Romidepsin (histone deacetylase inhibitor), lenalidomide (immunomodulatory agent), and carfilzomib (proteasome inhibitor), have efficacy and lack cumulative toxicity in relapsed/refractory lymphoma. We performed two investigator initiated sequential phase I studies to evaluate the maximum tolerated dose (MTD) of romidepsin and lenalidomide (regimen A) and romidepsin, lenalidomide, and carfilzomib (regimen B) in relapsed/refractory lymphoma. Cohorts in T-cell lymphoma (TCL), B-cell lymphoma (BCL) were enrolled at the MTD.

Phase I/II trial of the CXCR4 inhibitor plerixafor in combination with bortezomib as a chemosensitization strategy in relapsed/refractory multiple myeloma.

We tested the hypothesis that using CXCR4 inhibition to target the interaction between the tumor cells and the microenvironment leads to sensitization of the tumor cells to apoptosis. Eligibility criteria included multiple myeloma (MM) patients with 1-5 prior lines of therapy. The purposes of the phase I study were to evaluate the safety and maximal-tolerated dose (MTD) of the combination.

Brincidofovir for polyomavirus-associated nephropathy after allogeneic hematopoietic stem cell transplantation.

Polyomavirus-associated nephropathy (PVAN) is common in patients who have undergone kidney transplantation and has been reported in hematopoietic stem cell (HSC) transplant recipients. Aside from reduction of immunosuppression, few therapeutic options exist for treatment of PVAN. We report a case of PVAN in a severely immunocompromised allogeneic HSC transplant recipient that was treated with brincidofovir without reduction of immunosuppression.

Acute myeloid leukemia following solid organ transplantation: case report and comprehensive review.

Organ transplant recipients are at an increased risk for subsequent malignancies including hematologic malignancies. The development of acute myeloid leukemia (AML) after solid organ transplantation is a rare but well-documented event. It is thought to be a consequence of immune dysregulation secondary to the use of immunosuppressive agents.

Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes.

Background: Romiplostim is a peptibody protein that augments thrombopoiesis by activating the thrombopoietin receptor.

Methods: In this phase 2, multicenter, open-label study, 28 thrombocytopenic patients with lower risk myelodysplastic syndromes (MDS) were assigned to receive romiplostim 750 μg administered subcutaneously either weekly or biweekly or administered as biweekly intravenous injections for 8 weeks. Patients also could enter a 1-year study extension phase.

Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia.

Purpose: To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS).

Patients And Methods: Eligible patients had lower-risk MDS (International Prognostic Scoring System low or intermediate 1), a mean baseline platelet count View Article and Find Full Text PDF

Thrombocytopenia in myelodysplastic syndromes and myelofibrosis.

Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders characterized by ineffective hematopoeisis and an increased risk of transforming to acute myelogenous leukemia (AML). Determining the molecular basis of the disease has been hampered by its heterogeneity. Thrombocytopenia is often a manifestation of MDS and needs to be monitored and treated accordingly.

CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy.

Despite advances in therapy, many patients with systemic light-chain amyloidosis (AL) die within 3 years from diagnosis. The humanized 2B6 monoclonal antibody (MoAb) is specific for the low-affinity IgG Fc receptor CD32B and effective in a human CD32B+ B-cell lymphoma murine xenograft model. Because MoAb therapy could improve outcomes in AL, we studied CD32B expression by clonal plasma cells obtained from 48 patients with AL.

Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions.

Human monocyte-derived DCs (moDCs) and circulating conventional DCs coexpress activating (CD32a) and inhibitory (CD32b) isoforms of IgG Fcgamma receptor (FcgammaR) II (CD32). The balance between these divergent receptors establishes a threshold of DC activation and enables immune complexes to mediate opposing effects on DC maturation and function. IFN-gamma most potently favors CD32a expression on immature DCs, whereas soluble antiinflammatory concentrations of monomeric IgG have the opposite effect.

Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83.

We have studied the mechanisms by which human cytomegalovirus (HCMV) infection of monocyte-derived dendritic cells (moDCs) contribute to immune suppression. Unlike infection of immature moDCs, infection of mature moDCs is not lytic and results in minimally decreased surface major histocompatibility complex (MHC) and costimulatory molecule expression. The presence of a small percentage of CMV-infected mature moDCs, or the transfer of supernatant from infected moDCs depleted of infectious virions, is nevertheless sufficient to cause marked inhibition of immunostimulation by normal uninfected moDCs.