[Show abstract][Hide abstract] ABSTRACT: Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant non-Hodgkin's lymphoma (NHL). Here we studied whether Bi20 (FBTA05), a novel trifunctional bispecific antibody targeting CD20 on lymphoma cells and CD3 on T cells, could induce GVL responses in combination with DLI or mobilized PBSCT after allogeneic transplantation in these diseases. Six patients (three cases with p53-mutated CLL and three with high-grade NHL (HG-NHL)) refractory to standard therapy were treated with escalating doses of Bi20 (range 10-2000 microg) followed by DLI or SCT. Thereby, all CLL patients showed a prompt but transient clinical and hematological response. In one patient with HG-NHL, we observed a halt in progression for almost 4 months. Side effects (fever, chills and bone pain) were tolerable and appeared at antibody dose levels between 40 and 200 microg. The cytokine profile was characterized by transient increases of IL-6, IL-8 and IL-10. Neither human anti-mouse antibodies nor GVHD developed, allowing repeated treatment courses. In summary, the trifunctional antibody Bi20 induced prompt antitumor responses in extensively pretreated, p53-mutated alemtuzumab and rituximab refractory patients indicating its therapeutic potential.
Full-text · Article · Nov 2008 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: Allogeneic stem cell transplantation may induce lasting remissions in leukemia and hematological malignancies that otherwise are refractory to chemotherapy. An important role in the control of the disease is played by immune competent cells of the graft. This role has been most convincingly demonstrated by the effect of donor lymphocyte transfusions for the treatment of recurrent chronic myelogenous leukemia. In other forms of leukemia and hematological malignancies this role has been less clearly defined. In this chapter, strategies are discussed to improve the effect of donor lymphocyte transfusions. Methods to improve responses have involved the use of cytokines, natural killer cells, and antibodies.