A randomized study of melphalan 200 mg/m2 vs 280 mg/m2 as a preparative regimen for patients with multiple myeloma undergoing auto-SCT

To examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in myeloma (MM) patients. Patients with MM, N= 131, were randomized to 200 mg/m(2) (mel200) v. 280 mg/m(2) (mel280) using amifostine pretreatment. The primary endpoint was the proportion of patients achieving ≥nCR. No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 v. mel280, respectively, ≥nCR 22% v. 39%, p=0.03, ≥PR 57% v. 74%, p= 0.04. The hazard of mortality was not statistically significantly different between groups (mel200 v. mel280; HR=1.15 (95% CI, 0.62 to 2.13, p=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52 to 1.27, p=0.36)). The estimated progression-free survival at 1 and 3 years was 83% and 46%, respectively, for mel200 and 78% and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade-4 regimen-related toxicities and only 1 grade-3 mucositis (none with mel200) and 3 grade-3 GI toxicities (2 in mel200). Hospitalization rates were more frequent in the mel280 group (59% v. 43%, p=0.08). Mel280 resulted in a higher major response rate (CR+nCR)_ and should be evaluated in larger studies

Immunity to Aspergillus fumigatus: the basis for immunotherapy and vaccination

Efficient responses to fungi require different mechanisms of immunity. Dendritic cells (DCs) are uniquely able to decode the fungus-associated information and translate it into qualitatively different T helper (Th) immune responses. Murine and human DCs phagocytose conidia and hyphae of Aspergillus fumigatus through distinct recognition receptors. The engagement of distinct receptors translates into disparate downstream signaling events, ultimately affecting cytokine production and co-stimulation. Adoptive transfer of different types of DCs activates protective and non-protective Th cells as well as regulatory T cells, ultimately affecting the outcome of the infection in mice with invasive aspergillosis. The infusion of fungus-pulsed or RNA-transfected DCs also accelerates recovery of functional antifungal Th 1 responses in mice with allogeneic hematopoietic stem cell transplantation. Patients receiving T cell-depleted allogeneic hematopoietic stem cell transplantation are unable to develop antigen-specific T cell responses soon after transplant due to defective DC functions. Our results suggest that the adoptive transfer of DCs may restore immunocompetence in hematopoietic stem cell transplantation by contributing to the educational program of T cells. Thus, the remarkable furictional plasticity of DCs can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to the fungus