Multiple myeloma.

This update provides new insights into the biology, diagnosis, prognosis, and treatment of multiple myeloma (MM) and its complications. In Section I, Drs. John Shaughnessy, Jr., and Bart Barlogie first correlate global gene microarray expression profiling of patient MM samples with normal plasma cells to provide the basis for a developmental stage-based classification of MM. The powerful clinical utility of these analyses is illustrated in delineating mechanism of drug action, identifying novel therapeutic targets, and providing a molecular analysis not only of the tumor cell, but also of the tumor microenvironment, in MM. In Section II, Dr. Jean-Luc Harousseau reviews the rationale and current results of high dose therapy and autologous stem cell transplantation in MM, including optimal patient selection, prognostic factors, conditioning regimens, sources of stem cells, use of tandem transplantation, and maintenance therapy. He then provides an update on the results of allotransplantation approaches in MM, focusing on proposed methods to reduce toxicity and exploit the graft-versus-MM alloimmune effect by transplantation earlier in the disease course, T cell depletion, and nonmyeloablative transplantation. In Section III, Dr. G. David Roodman provides recent insights into the mechanisms of osteoclast activation, interactions between bone and MM cells, adhesive interactions in MM bone disease, and osteoblast suppression. These recent advances not only provide insights into pathogenesis of MM bone disease, but also form the framework for novel therapeutics. In Section IV, Dr. Kenneth Anderson provides an up-to-date discussion of the role of the bone marrow microenvironment in promoting growth, survival, drug resistance, and migration of MM cells and the signaling cascades mediating these sequelae. These studies provide the framework for evaluation of novel therapeutics targeting the MM cell-host interaction in vivo in animal models and in derived clinical trials.