Sequential analysis of bone marrow and peripheral blood after stem cell transplant for myeloma shows disparate tumor involvement

Abstract

Treatment with combination chemotherapy has not resulted in long-term remissions in multiple myeloma (MM) despite advances in drug discovery and protocol improvement over the last 25 years. Increasingly, peripheral blood (PB) stem cell transplants (PBSCT) are being used along with chemotherapy and total body irradiation as treatment for multiple myeloma. Although the majority of tumor cells are found within the bone marrow (BM), tumor cells circulate in the PB in patients with MM. Therefore, one potential problem with PBSCT is contamination of the stem cell harvests with tumor cells. Although substantial reduction in BM tumor load is achieved after chemotherapy and autologous transplantation, most patients still relapse. In an attempt to identify and quantitate the residual tumor within sequential BM and PB samples of patients with MM following autologous PB stem cell transplants we have used a tumor-specific detection assay, allele-specific oligonucleotide-PCR (ASO-PCR). We found that while the BM tumor burden may fluctuate in some patients by as much as 4-logs after transplant, the PB tumor remains quite stable, and does not reflect the tumor burden in the BM. Moreover, analysis of PB involvement over time was not predictive of marrow involvement or of potential relapse. These results suggest that the PB is frequently involved in MM and further indicate that it represents a compartment that is only minimally altered by intensive therapy.