Biology and therapy of multiple myeloma

Bone marrow plasma cells of patients with myeloma are frequently aneuploid, have a high RNA content and typically show monoclonal immunoglobulin in their cytoplasm. Kappa-lambda co-expression in aneuploid tumor cells was restricted to patients with IgG lambda myeloma. Immunophenotype studies revealed early B cell expression often in association with mature B cell markers. Chromosomal aberrations were complex with a predominance of numeric but also structural lymphoma-type translocations; the latter were most prevalent in IgA myeloma. Specific translocations such as t(8;14) and t(11;14) were accompanied by aberrations of c-myc and bcl-l cellular genes. Effective salvage programs have been developed for melphalan-prednisone refractory myeloma. In comparing high-dose dexamethasone with vincristine-adriamycin + dexamethasone (VAD), VAD was superior particularly for relapsing myeloma (response rate of 60 vs. 23%). For VAD refractory myeloma, high-dose melphalan (HDM) programs were developed; total body irradiation (850 rad) followed by HDM 140 mg/m2 and supported by autologous bone marrow grafts was particularly effective and relatively well tolerated with all 4 patients still in remission from 3 to 15 months.