ABSTRACT
Treatment related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) are well known complications after chemotherapy for various hematologic and non-hematologic malignancies. Alkylating agents and Topoisomerase inhibitors are most widely studied in this regard. There is growing concern about occurrence of t-MDS, t-MDS/AML and t-AML in patients of CLL treated with nucleoside analogues especially in combination with alkylating agents. Exact incidence and pathogenesis of nucleoside analogue related MDS/AML is not clear at this time. We hereby report a case of t-AML in a patient treated with Fludarabine, Cyclophosphamide and Rituximab (FCR) for CLL. The cytogenetic studies revealed a unique translocation t (10:16), that has been reported in very few cases of therapy related AML and pediatric AML.
ABSTRACT
2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and FcgammaRIII. 2B1 efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the FcgammaRIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2B1 therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but 1 patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m/d to 1 mg/m/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate antibody-directed cellular cytotoxicity may exert their clinical antitumor effects.