Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Herein we report results of a phase I/II trial to evaluate the safety and activity of autologous T-cells engineered to express an affinity-enhanced T-cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4×109 engineered T cells two days after autologous stem cell transplant (ASCT). Infusions were well-tolerated without clinically apparent cytokine release syndrome, despite high IL-6 levels. Engineered T-cells expanded, persisted, trafficked to marrow and exhibited a cytotoxic phenotype. Persistence of engineered T cells in blood was inversely associated with NY-ESO-1 levels in the marrow. Disease progression was associated with loss of T cell persistence or antigen escape, consistent with the expected mechanism of action of the transferred T cells. Encouraging clinical responses were observed in 16 of 20 patients (80%) with advanced disease, with a median progression free survival of 19.1 months. NY-ESO-1/LAGE-1 TCR-engineered T-cells were safe, trafficked to marrow and showed extended persistence that correlated with clinical activity against antigen-positive myeloma.

Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever.

Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers.

The primary cause of death (COD) provides important information in many studies of hematopoietic stem cell transplantation (HSCT). A panel of experts critically assessed the CODs submitted by 15 transplantation centers for 281 patients who died in a randomized multicenter trial of unrelated HSCT. The panel reviewed the CODs reported by the transplantation centers, which used the Center for International Blood and Marrow Transplant Research and National Marrow Donor Program COD reporting form. The panel determined that the existing criteria for primary and contributing CODs lacked sufficient stringency for uniform interpretation. A hierarchy was developed and applied to the T cell depletion project. Using its scheme, the panel reclassified 157 CODs (56%) reported by the transplantation centers. The changes resulted in increased recognition of graft-versus-host disease as the primary COD and a concomitant decrease in attribution of the primary COD to infection. This algorithm promotes consistent assignment of primary and contributing CODs for patients with leukemia or lymphoma who expire after myeloablative allogeneic HSCT.