Studies on the Clonogenicity of Human Myeloma Cells in vitro

Myeloma is a disease of the B cell lineage which is characterized by the presence of excess numbers of isotypic plasma cells in the bone marrow and a serum paraprotein which is also isotypic for individual patients. These critieria may be accompanied by bone pain and often renal impairment. Until recently the median survival for patients treated with conventional chemotherapy was 2 years, however at the Royal Marsden Hospital (RMH) the use of VAMP (vincris-tine, 0.4 mg daily, days 1-4), adriamycin 9 mg/m(2) daily, days 1-4) and methylprednisolone (1 g/m(2) daily, days 1-5) followed by high-dose melphalan at 140 mg/m(2) or 200 mg/m(2) with autologous bone marrow transplantation has increased this survival time to 5 years in previously untreated patients(1,2). During the past 5 years the myeloma practice at the RMH has increased considerably and regular bone marrow aspirates from patients provide the material for in vitro studies. At present there: are approximately 160 patients whose disease is available for monitoring in vitro and approximately 15 myelomatous bone marrow are processed each week. The principal questions that need to be answered in myeloma is why do some patients fail to respond to chemotherapy and why does a further group become refractory to treatment at relapse. These problems encompass a need to examine drug-induced or endogenous drug resistance and to study the lineage of the disease. The development of an in vitro assay for myeloma colony formation by our group is enabling these questions to be investigated(3,4).