The relationship between monoclonal myeloma precursor B cells in the peripheral blood stem cell harvests and the clinical response of multiple myeloma patients

Abstract

The aim of this study was to determine the presence of monoclonal myeloma precursor B cells in peripheral blood stem cell harvests and to investigate their role in the clinical outcome of multiple myeloma patients. A total of 39 multiple myeloma patients were treated with a sequential therapy including double high‐dose melphalan therapy followed by a double transplant procedure. The apheresis products for the second transplant were purged using a panel of four or five different mouse monoclonal antibodies against B‐cell antigens (CD10, CD19, CD20, CD22 and CD37). In 19/39 patients a tumour‐specific CDR III signal was identified in the diagnostic bone marrow. Gene scan analysis after CDR III PCR of the magnetic bead isolated B‐cell fraction from the apheresis products in these 19 patients revealed three different patterns: 32% of patients had a predominantly monoclonal B‐cell population; 63% of patients had an identifiable monoclonal signal within an oligoclonal B‐cell population. In only 1/19 patients were no monoclonal B cells identified in the B‐cell population of the apheresis product. A correlation between the clonal pattern and the clinical response after sequential chemotherapy was found. Patients with a predominance of monoclonal myeloma or myeloma precursor B cells had an early relapse or achieved a minimal response or a partial remission. Patients with an oligo‐ and/or polyclonal pattern achieved a high percentage of partial as well as complete remissions.

Transendothelial Migration of Myeloma Cells Is Increased by Tumor Necrosis Factor (TNF)-α via TNF Receptor 2 and Autocrine Up-Regulation of MCP-1

“…plasma cells has been shown to predict survival (27). Furthermore, the number of malignant precursor cells in mobilized peripheral blood stem cell harvests has also been inversely correlated with the duration of disease-free intervals (28). However, it cannot be excluded that in these patients, disease progression might also be due to a small fraction of therapyresistant plasma cells below detection levels.…”

High-dose melphalan with G-CSF-stimulated whole blood rescue followed by stem cell harvesting and busulphan/cyclophosphamide with autologous stem cell transplantation in multiple myeloma

“…19 Since almost all grafts harvested before going to single or double transplants contain monoclonal myeloma precursor B cells, it could be an advantage to develop a strategy including a second stem cell harvest after the first transplant to be reinfused after the second high-dose chemotherapy, in order to minimise myeloma cell contamination of the graft. 20 We report on the results of such a strategy, both in untreated and pre-treated patients. In our double transplant approach, we utilised the G-CSF-stimulated whole blood transplant procedure for rescue after the first, high-dose melphalan containing chemotherapy, a technique we introduced in 1996.…”

Characterization of clonogenic multiple myeloma cells

“…Several investigators have proposed that these clonally related B cells represent the proliferating compartment or tumor "stem cells" in MM; however, this remains a matter of debate because these cells have not been functionally characterized. [9][10][11][12][13][14] Syndecan-1 (CD138) is expressed by malignant plasma cells from the majority of MM cell lines and patient specimens. [15][16][17] Furthermore, during normal B-cell development, CD138 expression is highly specific for terminally differentiated normal plasma cells because it is absent on highly proliferative normal plasmablasts and all earlier B-cell stages.…”