Molecular Characterization of Mobilized Apheresis Hematopoietic Progenitor Cells Designated for Autologous Stem Cell Transplantation in Multiple Myeloma

ABSTRACT Introduction Multiple myeloma is the second most common malignancy of the lymphoid system and accounts for about 2% of cancer deaths. Treatment generally consists of chemotherapy and autologous stem cell transplantation. Clinical trial results are equivocal as to whether autologous stem cell transplantation in the treatment of multiple myeloma prolongs overall survival. One possible etiology for this conundrum could be that the transplanted autologous stem cells may also contain residual tumor cells/tumor stem cells. Methods Residual autologous stem cells from patients undergoing stem cell transplantation were examined for cells containing monoclonal immunoglobulins and clonotypic DNA detected in diagnostic bone marrow to determine if malignant myeloma cells may have been transplanted along with hematopoietic stem cells. Results In all eight cases of autologous stem cell transplants examined from multiple myeloma patients, the infused cells included cells containing monoclonal immunoglobulins of the same type as were noted in patients' sera at the time of diagnosis. This was not seen in allogeneic cells from donors without cancer. In all four cases in which a dominant clone was identified by molecular analysis in the diagnostic bone marrow, the same clone was detectable in the autologous stem cells. Conclusions We posit that lack of prolongation of overall survival with autologous stem cell transplantation in multiple myeloma is in part due to infusion of cells containing tumor cells that repopulate the recipient. This finding may warrant novel collection and processing strategies to mitigate the infusion of malignant cells. Until such methods become available, the use of autologous stem cell transplantation should be considered in the context of the conundrum reported here. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission