HEMATOLOGIC ONCOLOGY

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DESCRIPTION: (Applicant's Description) The overall aims of the Hematologic Oncology Project are to develop and test new and effective strategies for treating hematologic neoplasms using targeted therapies and biologic agents. The SPECIFIC AIMS for this revised proposal are to: Develop novel therapeutic strategies in hematologic malignancies, including a) histone deacetylase inhibitors, such as depsipeptide b) geldanamycin in the treatment of CML c) desoxyepothiline B in the treatment of non-Hodgkin's Iymphoma. Evaluate the use of targeted therapies using: a)monoclonal antibodies in dose-intense strategies, with autologous stem cell support for myeloid leukemias and myelodysplastic syndromes, using a radio labeled humanized monoclonal antibody (HuMl95; anti-CD33) to deliver targeted radiotherapy b)monoclonal antibodies for treatment of minimal residual disease in acute promyelocytic leukemia using all-trans retinoic acid for induction, followed by unlabeled HuM195, arsenic trioxide, and then idarubicin for consolidation c) ''tumor-specific'' vaccine approaches in patients with peptide vaccine in patients with myelodysplastic syndromes or AML. Evaluate tumor specific endpoints using a)Correlative in vitro assays of HDAC inhibition b) Serial quantitative levels of BCR-ABL protein (or rnRNA) c) MR Spectroscopy to assess response (for d) RT-PCR based assays to detect residual APL cells.