Only few patients with myeloma diseases have been cured so far. It is the hypothesis of this proposed research programe that a myeloma hierarchy exists, which include chemoresistant progenitors identified as oncogene positive memory B cells. These cells are very low frequent and circulating cells present in blood, marrow and lymph node are potential malignant dormant Òmyeloma stem cellsÓ, which may be responsible for and feed posttransplant disease recurrence (the feeder-sleeper theory). The clinical impact of these cells is at present unknown and needs to be studied by analyzing the toxicity, safety and efficacy of highly selected targeted therapy e.g. by Fludarabine or vaccination in randomized phase II multicenter trials.