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Quantitative comparison of multiple myeloma tumor contamination in bone marrow harvest and leukapheresis autografts
R A Vescio1, E J Han, G J Schiller
1Division of Hematology/Oncology, DVA West Los Angeles, CA 90073, USA.
Abstract:
Autologous transplantation is increasingly being used to treat patients with multiple myeloma (MM). Recently, peripheral blood progenitor cell (PBPC) harvest have been preferred over autologous bone marrow (BM) harvests due to reduced engraftment time, ease of attainment, and presumptive reduction of occult tumor involvement. To resolve this latter assumption quantitatively, we have used the unique immunoglobulin (Ig) heavy chain variable region sequence of the patient's myeloma cell as a marker of clonality. Samples from PBPC collections and 'back-up' BM harvests were obtained from 13 patients with MM and analyzed for tumor contamination using patient-specific oligonucleotide primers and the polymerase chain reaction. As expected, the percentage of tumor cells contaminating the BM harvest (median, 0.74%) was higher than in the PBPC specimens (median, 0.0024%). Because of the increased total number of cells required for PBPC transplantation, the increase in total number of contaminating cells in the BM vs PBPC autografts was less pronounced, (BM:PBPC tumor contamination ratios ranging from 0.9 to > 4500; median, 14). This confirms that in most but not all cases unmanipulated PBPC products are preferable over BM harvests as a method of reducing myeloma autograft tumor contamination.
Insights
Peripheral blood progenitor cell (PBPC) harvests show significantly lower tumor cell contamination than bone marrow (BM) harvests in multiple myeloma (MM) autotransplantation. This makes PBPC a preferable method for reducing tumor burden in MM patients undergoing transplantation.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Autologous transplantation is a key treatment for multiple myeloma (MM).
- Peripheral blood progenitor cell (PBPC) harvests are increasingly favored over bone marrow (BM) harvests.
- PBPC harvests offer benefits like faster engraftment and easier collection, with a presumed reduction in tumor cell contamination.
Purpose of the Study:
- To quantitatively assess and compare tumor cell contamination in PBPC versus BM harvests for autologous transplantation in MM patients.
- To validate the assumption that PBPC harvests have lower occult tumor involvement compared to BM harvests.
Main Methods:
- Utilized patient-specific immunoglobulin (Ig) heavy chain variable region sequences as markers of myeloma cell clonality.
- Analyzed samples from PBPC collections and 'back-up' BM harvests from 13 MM patients.
- Employed polymerase chain reaction (PCR) with patient-specific oligonucleotide primers to detect tumor cell contamination.
Main Results:
- BM harvests exhibited a higher median percentage of tumor cell contamination (0.74%) compared to PBPC specimens (0.0024%).
- Despite higher contamination percentages in BM, the overall increase in contaminating cells was less pronounced due to the larger cell numbers in PBPC transplants (median BM:PBPC ratio of 14).
- This confirms PBPC products are generally superior for reducing myeloma autograft tumor contamination.
Conclusions:
- Unmanipulated PBPC products are preferable to BM harvests for reducing tumor cell contamination in autologous transplantation for multiple myeloma.
- While PBPC significantly reduces contamination, it is not entirely eliminated in all cases.
- This finding supports the routine use of PBPC for MM autotransplantation to minimize tumor burden.