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Tumour Cell Contamination

Gene scanning of VDJH-amplified segments is a clinically relevant technique to detect contaminating tumor cells in the apheresis products of multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation

Abstract

Contaminating tumour cells in apheresis products have proved to influence the outcome of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (APBSCT). The gene scanning of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) is a reproducible and easy to perform technique that can be optimised for clinical laboratories. We used it to analyse the aphereses of 27 MM patients undergoing APBSCT with clonally detectable VDJH segments, and 14 of them yielded monoclonal peaks in at least one apheresis product. The presence of positive results was not related to any pre-transplant characteristics, except the age at diagnosis (lower in patients with negative products, P = 0.04). Moreover, a better pre-transplant response trended to associate with a negative result (P = 0.069). Patients with clonally free products were more likely to obtain a better response to transplant (complete remission, 54% vs 28%; >90% reduction in the M-component, 93% vs 43% P = 0.028). In addition, patients transplanted with polyclonal products had longer progression-free survival, (39 vs 19 months, P = 0.037) and overall survival (81% vs 28% at 5 years, P = 0.045) than those transplanted with monoclonal apheresis. In summary, the gene scanning of apheresis products is a useful and clinically relevant technique in MM transplanted patients. Bone Marrow Transplantation (2001) 28, 665–672.

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References

  1. San Miguel JF, Bladé CJ, García-Sanz R . Treatment of multiple myeloma Haematologica 1999 84: 36–58

    CAS  Google Scholar 

  2. Attal M, Harousseau JL, Stoppa AM et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome New Engl J Med 1996 335: 91–97

    Article  CAS  Google Scholar 

  3. Boccadoro M, Pileri A . Diagnosis, prognosis, and standard treatment of multiple myeloma Hematol Oncol Clin North Am 1997 11: 111–131

    Article  CAS  Google Scholar 

  4. Tricot G, Jagannath S, Vesole D et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients Blood 1995 85: 588–596

    CAS  Google Scholar 

  5. Haas R, Mohle R, Fruhauf S et al. Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma Blood 1994 83: 3787–3794

    CAS  Google Scholar 

  6. Goldschmidt H, Hegenbart U, Wallmeier M et al. Factors influencing collection of peripheral blood progenitor cells following high-dose cyclophosphamide and granulocyte colony-stimulating factor in patients with multiple myeloma Br J Haematol 1997 98: 736–744

    Article  CAS  Google Scholar 

  7. Mahe B, Milpied N, Hermouet S et al. G-CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma Br J Haematol 1996 92: 263–268

    Article  CAS  Google Scholar 

  8. Bellos F, Cremer FW, Ehrbrecht E et al. Leukapheresis cells of patients with multiple myeloma collected after mobilization with chemotherapy and G-CSF do not bear Kaposi's sarcoma associated herpesvirus DNA Br J Haematol 1998 103: 1192–1197

    Article  CAS  Google Scholar 

  9. López-Pérez R, García-Sanz R, González M et al. The detection of contaminating clonal cells in apheresis products is related to response and outcome in multiple myeloma undergoing autologous peripheral blood stem cell transplantation Leukemia 2000 14: 1493–1499

    Article  Google Scholar 

  10. Brenner MK, Rill DR, Holladay MS et al. Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients Lancet 1993 342: 1134–1137

    Article  CAS  Google Scholar 

  11. Gertz MA, Witzig TE, Pineda AA et al. Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation Bone Marrow Transplant 1997 19: 337–342

    Article  CAS  Google Scholar 

  12. Dreyfus F, Ribrag V, Leblond V et al. Detection of malignant B cells in peripheral blood stem cell collections after chemotherapy in patients with multiple myeloma Bone Marrow Transplant 1995 15: 707–711

    CAS  PubMed  Google Scholar 

  13. Witzig TE, Gertz MA, Pineda AA et al. Detection of monoclonal plasma cells in the peripheral blood stem cell harvests of patients with multiple myeloma Br J Haematol 1995 89: 640–642

    Article  CAS  Google Scholar 

  14. Witzig TE, Kyle RA, O'Fallon WM, Greipp PR . Detection of peripheral blood plasma cells as a predictor of disease course in patients with smouldering multiple myeloma Br J Haematol 1994 87: 266–272

    Article  CAS  Google Scholar 

  15. Mitterer M, Oduncu F, Lanthaler AJ et al. The relationship between monoclonal myeloma precursor B cells in the peripheral blood stem cell harvests and the clinical response of multiple myeloma patients Br J Haematol 1999 106: 737–743

    Article  CAS  Google Scholar 

  16. Schiller G, Vescio R, Freytes C et al. Transplantation of CD34+ peripheral blood progenitor cells after high-dose chemotherapy for patients with advanced multiple myeloma Blood 1995 86: 390–397

    CAS  Google Scholar 

  17. Vescio R, Schiller G, Stewart AK et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma Blood 1999 93: 1858–1868

    CAS  Google Scholar 

  18. Vescio RA, Han EJ, Schiller GJ et al. Quantitative comparison of multiple myeloma tumor contamination in bone marrow harvest and leukapheresis autografts Bone Marrow Transplant 1996 18: 103–110

    CAS  Google Scholar 

  19. Corradini P, Voena C, Astolfi M et al. High-dose sequential chemoradiotherapy in multiple myeloma: residual tumor cells are detectable in bone marrow and peripheral blood cell harvests and after autografting Blood 1995 85: 1596–1602

    CAS  Google Scholar 

  20. Lemoli RM, Fortuna A, Motta MR et al. Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells Blood 1996 87: 1625–1634

    CAS  Google Scholar 

  21. Cremer FW, Kiel K, Wallmeier M et al. Leukapheresis products in multiple myeloma: lower tumor load after mobilization with cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) compared with G-CSF alone Exp Hematol 1998 26: 969–975

    CAS  PubMed  Google Scholar 

  22. Bird JM, Russell NH, Samson D . Minimal residual disease after bone marrow transplantation for multiple myeloma: evidence for cure in long-term survivors Bone Marrow Transplant 1993 12: 651–654

    CAS  Google Scholar 

  23. Mariette X, Fermand JP, Brouet JC . Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy Bone Marrow Transplant 1994 14: 47–50

    CAS  Google Scholar 

  24. Langerak AW, Szczepanski T, van der Burg M et al. Heteroduplex PCR analysis of rearranged T cell receptor genes for clonality assessment in suspect T cell proliferations Leukemia 1997 11: 2192–2199

    Article  CAS  Google Scholar 

  25. The Chronic Leukemia–Myeloma Task Force . Proposed guidelines for protocol studies. I. Introduction. II. Plasma cell myeloma. 3. Chronic lymphocytic leukemia. IV. Chronic granulocytic leukemia Cancer Chemother Rep 1973 4: 141–173

    Google Scholar 

  26. García-Sanz R, López-Pérez R, Langerak AW et al. Heteroduplex PCR analysis of rearranged immunoglobulin genes for clonality assessment in multiple myeloma Haematologica 1999 84: 328–335

    PubMed  Google Scholar 

  27. Alegre A, Díaz-Mediavilla J, San-Miguel J et al. Autologous peripheral blood stem cell transplantation for multiple myeloma: a report of 259 cases from the Spanish Registry. Spanish Registry for Transplant in MM (Grupo Español de Trasplante Hematopoyetico-GETH) and PETHEMA. Comparison of peripheral blood progenitor cell mobilization in patients with multiple myeloma: high-dose cyclophosphamide plus GM-CSF vs G-CSF alone Bone Marrow Transplant 1998 21: 133–140

    Article  CAS  Google Scholar 

  28. Pérez-Simón JA, Caballero MD, Corral M et al. Minimal number of circulating CD34+ cells to ensure successful leukapheresis and engraftment in autologous peripheral blood progenitor cell transplantation Transfusion 1998 38: 385–391

    Article  Google Scholar 

  29. Lahuerta JJ, Martínez-Lopez J, Serna JD et al. Remission status defined by immunofixation vs electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients Br J Haematol 2000 109: 438–446

    Article  CAS  Google Scholar 

  30. Bladé J, Samson D, Reece D et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant Br J Haematol 1998 102: 1115–1123

    Article  Google Scholar 

  31. Almeida J, Orfao A, Ocqueteau M et al. High-sensitive immunophenotyping and DNA ploidy studies for the investigation of minimal residual disease in multiple myeloma Br J Haematol 1999 107: 121–131

    Article  CAS  Google Scholar 

  32. González M, González D, López-Pérez R et al. Heteroduplex analysis of VDJ amplified segments from rearranged IgH genes for clonality assessments in B-cell non-Hodkin's lymphoma. A comparision between different strategies Haematologica 1999 84: 779–784

    PubMed  Google Scholar 

  33. Corradini P, Voena C, Tarella C et al. Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells J Clin Oncol 1999 17: 208–215

    Article  CAS  Google Scholar 

  34. Martinelli G, Terragna C, Lemoli R et al. Clinical and molecular follow-up by amplification of the CDR-III IgH region in multiple myeloma patients after autologous transplantation of hematopoietic CD34+ stem cells Haematologica 1999 84: 397–404

    CAS  PubMed  Google Scholar 

  35. Lemoli RM, Cavo M, Fortuna A . Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of patients with multiple myeloma J Hematother 1996 5: 339–349

    Article  CAS  Google Scholar 

  36. Björkstrand B, Ljungman P, Bird JM et al. Double high-dose chemoradiotherapy with autologous stem cell transplantation can induce molecular remissions in multiple myeloma Bone Marrow Transplant 1995 15: 367–371

    Google Scholar 

  37. Dreyfus F, Melle J, Quarre MC, Pillier C . Contamination of peripheral blood by monoclonal B cells following treatment of multiple myeloma by high-dose chemotherapy Br J Haematol 1993 85: 411–412

    Article  CAS  Google Scholar 

  38. Swedin A, Lenhoff S, Olofsson T et al. Clinical utility of immunoglobulin heavy chain gene rearrangement identification for tumour cell detection in multiple myeloma Br J Haematol 1998 103: 1145–1151

    Article  CAS  Google Scholar 

  39. Bird JM, Bloxham D, Samson D et al. Molecular detection of clonally rearranged cells in peripheral blood progenitor cell harvests from multiple myeloma patients Br J Haematol 1994 88: 110–116

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Mark Anderson and Felicitación García for their technical assistance. This work has been partially supported with the grant number 99/1243 from the Spanish ‘Fondo de Investigaciones Sanitarias’ and the grant 1997 from the ‘Areces Foundation’.

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López-Pérez, R., García-Sanz, R., González, D. et al. Gene scanning of VDJH-amplified segments is a clinically relevant technique to detect contaminating tumor cells in the apheresis products of multiple myeloma patients undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 28, 665–672 (2001). https://doi.org/10.1038/sj.bmt.1703219

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