65: The use of cyclophosphamide (CY), fludarabine and ATG as a preparative regimen for unrelated cord blood transplantation (UCBT) in fanconi anemia (original) (raw)

2007, Biology of Blood and Marrow Transplantation

We have demonstrated that patient derived myeloma cells fused with autologous dendritic cells (DCs) potently stimulate anti-tumor immunity in vitro. We are conducting phase I clinical trials in which patients with myeloma undergo serial vaccination with DC/ myeloma fusions alone or in conjunction with stem cell transplantation. To date, 18 patients have been enrolled (11-vaccine alone, 7 vaccine following autologous stem cell transplant). To generate mature DCs, adherent mononuclear cells were isolated from a leukapharesis collection and cultured with GM-CSF, IL-4, and TNF␣ . The mean yield and viability of the DC preparations was 1.5 ϫ 10 8 cells and 88%, respectively. Patient derived myeloma cells were isolated from bone marrow aspirates and were quantified by the expression of CD38 and/or CD138. The mean yield and viability of the myeloma cell collections was 7.3 ϫ 10 7 cells and 89%, respectively. Fusion cells were generated by coculture of DCs with myeloma cells in the presence of 50% polyethylene glycol. The mean fusion efficiency was 40% as determined by the percentage of cells that co-expressed unique DC and myeloma antigens. In contrast to myeloma cells, the DC and fusion cell preparations prominently stimulated allogeneic T cell proliferation in vitro. To date, 13 patients have completed vaccination at a dose of 1-5 ϫ 10 6 fusion cells. GM-CSF (100 g) was administered subcutaneously on the day of vaccination and for 3 days thereafter. Adverse events judged to be potentially vaccine related have included vaccine injection site reactions, edema, rash, fever, chills, fatigue, muscle aches, pruritis, and diarrhea. One patient with a history of prior deep venous thrombosis (DVT) developed a DVT and pulmonary embolus of uncertain relation to the vaccine. To date, a majority of evaluable patients demonstrated evidence of vaccine induced anti-myeloma immunity as demonstrated by at least 2 fold increase in IFN␥ expression by CD4 and/or CD8 T cells in response to ex vivo exposure to autologous tumor lysate. Of patients undergoing vaccine therapy alone, 5 patients demonstrated stabilization of the myeloma paraprotein for 2-6 months following initiation of vaccination. Of 3 patients completing posttransplant vaccination, 2 patients demonstrated resolution of the persisting myeloma protein post-transplant and 1 patient demonstrated a transient increase followed by a decline in paraprotein levels post-transplant.