Support is requested for an integrated clinical-therapeutic and laboratory research program on GROWTH CONTROL OF MULTIPLE MYELOMA by a team of experienced investigators, most of whom have interacted closely for several years and have independent research support. The clinical Project I emphasizes a curative approach for newly diagnosed patients through dose-intensive cytotoxic chemotherapy requiring hemopoietic growth factor and stem cell support (""""""""Total Therapy""""""""). In addition, biological agents with the potential of exerting direct antitumor effect or activating and augmenting normal host-defense mechanisms (T and NK cells) will be evaluated in previously treated patients. In order to take advantage of the large patient population seen at our Center with this rare malignancy and related disorders, a comprehensive workup will be performed of cytogenetics, molecular genetics and cytokines. the derived Myeloma Data Base should prove useful for a deeper understanding of etiology, disease manifestations and progression. the clinical project and the associated Cores (Chromosome and Molecular Genetics; Cytokines; Data Management) will provide a cohesive framework for specific basic laboratory research projects examining the intricate cytokine network involved in myeloma growth and clinical symptoms manifestation (Project II); the molecular mechanisms of dexamethasone activity and resistance (Project III); as well as the growth-controlling contributions of autoreactive cells shedding immunoglobulin binding factor (CD16) (Project IV). These host cells may be subject to therapeutic manipulations by biological events investigated in Project I, mainly dexamethasone, IL-4, ivIg, interferons and all-trans-retinoic acid.
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