Enumeration of blood dendritic cells in patients with multiple myeloma at presentation and through therapy

Abstract

Multiple myeloma (MM) is a clonal B-cell malignancy characterised by excess bone marrow plasma cells, serum and/or urine paraprotein, immune paraesis, renal failure and lytic bone lesions. Dendritic cells (DC) are key players in the adaptive and innate immune responses, but reside in tissues, so are difficult to quantify in vivo. By enumerating the blood DC pool, we aim to examine the influence of MM disease and accompanying therapy on the DC system. We have shown, using the BDCA DC detection kit, that blood pDC and mDC numbers are suppressed at diagnosis in MM, and uniquely, monoclonal gammopathy of uncertain significance (MGUS) and patients with plasmacytoma. B-cell numbers were also significantly reduced in MM, MGUS and patients with plasmacytoma (p<or=0.005). Standard chemotherapy did not improve the number of mDC1 or pDC seen in the blood of patients with MM. The number of blood mDC1 improved transiently following auto hemopoietic stem cell transplantation, as numbers returned to within the normal range at engraftment and were maintained until D100. The number of blood mDC1 in patients taking thalidomide was also significantly higher than at relapse. These studies suggest that the defects in the B cell and blood DC pool is present in MGUS and plasmacytoma as well as patients with MM and can recover following therapy.