Advertisement

Bone Marrow Purging

  • M. C. Favrot
  • T. Philip
Part of the UICC International Union Against Cancer book series (UICCI)

Abstract

In the management of leukemia and malignant solid tumors [if one excepts the graft-versus-leukemia (GVL) effect of an allograft], bone marrow transplantation (BMT) is not therapeutic per se, but is simply a method designed to overcome myelotoxicity after high-dose chemotherapy. The main limitations of this method are graft-versus-host disease (GVHD) in allogenic BMT and the contamination of the graft by residual malignant cells in autologous BMT. A common approach, so-called purging, has been proposed to eliminate unwanted cells from the BM before its reinjection—either allogenic normal T cells responsible for GVHD or autologous malignant cells.

Keywords

Bone Marrow Transplantation Human Bone Marrow Autologous Bone Marrow Transplantation Rabbit Complement Complement Lysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    DeWitte T, Hoogenhout J, De Pauw B, Holdrinet R, Jansen J, Wessels J, Van Daal W, Hustinx K, Haanen C (1986) Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation. Blood 67: 1302Google Scholar
  2. 2.
    Reisner Y, Kapoor D, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B, Hodes MZ, Good RA, O’Reilly RJ (1983) Transplantation for severe combined immunodeficiency with HLA-A, B, D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 61: 341Google Scholar
  3. 3.
    Reisner Y (1983) Differential agglutination by soybean agglutinin of human leukemia and neuroblastoma cell lines: potential application to autologous bone marrow transplantation. Proc Natl Acad Sci USA 80: 6657PubMedCrossRefGoogle Scholar
  4. 4.
    Korbling M, Hess AD, Tutschka PJ, Kaiser H, Colvin MO, Santos GW (1987) 4hydroperoxycyclophosphamide: a model for eliminating residual human tumour cells and T-lymphocytes from the bone marrow graft. Br J Haematol 52: 89Google Scholar
  5. 5.
    Kluin-Nelemans HC, Martens ACM, Lowenberg B, Hagenbeek A (1984) No preferential sensitivity of clonogenic AML cells to Asta Z 7557. Leuk Res 8: 723PubMedCrossRefGoogle Scholar
  6. 6.
    Yeager AM, Kaizer J, Santos GW, Saral R, Colvin OM, Stuart RK, Braise HG, Burke PJ, Ambinder RF, Burns WH (1986) Autologous bone marrow transplantation in patient with acute non-lymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide. N Engl J Med 315: 141PubMedCrossRefGoogle Scholar
  7. 7.
    Gorin NC, Douay L, Laporte JP, Lopez M, Mary JY, Najman A, Salmon C, Aagerter P, Stachowiak J, David R, Pene F, Kantor G, Deloux J, Duhamel E, Van den Akker J, Gerota J, Parlier Y, Duhamel G (1986) Autologous bone marrow transplantation using marrow incubated with Asta Z 7557 in adult acute leukemia. Blood 67: 1367PubMedGoogle Scholar
  8. 8.
    Hervé P, Cahn JV, Plouvier E, Flesch M, Tamayo E, Leconte des Floris R, Peters A (1984) Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide). First clinical results. New Drugs 2: 245Google Scholar
  9. 9.
    Kaizer H, Stuart RK, Brookmeyer R, Beschorner WE, Braine HG, Burns WH, Fuller DJ, Korbling M, Mangan KF, Saral R, Sensenbrenner L, Shadduck RK, Shende AC, Tutschka PJ, Yeager AM, Zinkham WH, Colvin OM, Santos GW (1985) Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4hydroperoxycyclophosphamide to purge tumor cells. Blood 65: 1504PubMedGoogle Scholar
  10. 10.
    Hartmann O, Kalifa C, Beaujean F, Bayle C, Benhamou E, Lemerle J (1985) Treatment of advanced neuroblastoma with two consecutive high-dose chemotherapy regimens and ABMT. In: Evans AE, D’Angio O, Seeger RC (eds) Advances in neuroblastoma research. Alan R, iss, New York, pp 565–568Google Scholar
  11. 11.
    Chang TT, Gulati SC, Chou TC, Vega R, Gandola L, Ezzat Ibrahim SM, Yopp J, Colvin M, Clarkson BD (1985) Synergistic effect of 4-hydroperoxycyclophosphamide and etoposide on a human promyelocytic leukemia cell line (HL-60) demonstrated by computer analysis. Cancer Res 45: 2434PubMedGoogle Scholar
  12. 12.
    Sieber F, Spivak JL, Sutcliffe AM (1984) Selective killing of leukemic cells by merocyanine 540-mediated photosensitization. Proc Natl Acad Sci USA 81: 7584PubMedCrossRefGoogle Scholar
  13. 13.
    Reynolds CP, Reynolds DA, Frenkel EP, Graham Smith R (1982) Selective toxicity of 6hydroxydopamine and ascorbate for human neuroblastoma in vitro: a model for clearing marrow prior to autologous transplant. Cancer Res 42: 1331PubMedGoogle Scholar
  14. 14.
    Lebien TW, Stepan DE, Bartholomew RM, Stong RC, Anderson JM (1985) Utilization of a colony assay to assess the variables influencing elimination of leukemic cells from human bone marrow with monoclonal antibodies and complement. Blood 65: 945PubMedGoogle Scholar
  15. 14.
    Lebien TW, Stepan DE, Bartholomew RM, Stong RC, Anderson JM (1985) Utilization of a colony assay to assess the variables influencing elimination of leukemic cells from human bone marrow with monoclonal antibodies and complement. Blood 65: 945PubMedGoogle Scholar
  16. 16.
    Bast RC, De Fabriities P, Lipton J, Gelber R, Mayer C, Nadler L, Sallan S, Ritz J (1985) Elimination of malignant clonogenic cells from human bone marrow using multiple monoclonal antibodies and complement. Cancer Res 45: 499PubMedGoogle Scholar
  17. 17.
    Favrot MC, Philip I, Philip T, Pinkerton R, Lebacq AM, Forster K, Adeline P, Doré JF (1986) Bone marrow purging procedure in Burkitt lymphoma with monoclonal antibodies and complement. Quantification by a liquid cell culture monitoring system. Br J Cancer 64: 161Google Scholar
  18. 18.
    Waldman H, Hale G, Cividalli G, Weshler Z, Manor D, Rachmilewitz EA, Polliak A, Or R, Weiss L, Samul S, Brautbar C, Slavin S (1984) Elimination of graft-versus-host disease by in vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (Campath-1). Lancet 2: 483CrossRefGoogle Scholar
  19. 19.
    Stepan DE, Bartholomew RM, Lebien TW (1984) In vitro cytodestruction of human leukemic cells using murine monoclonal antibodies and human complement. Blood 63: 1120PubMedGoogle Scholar
  20. 20.
    Saarinenu M, Coccia PF, Gerson SL, Pelley R, Cheung NKV (1985) Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow. Cancer Res 45: 5969Google Scholar
  21. 21.
    Treleaven JG, Gibson FM, Ugelstad J, Rembaum A, Philip T, Caine GD, Kemshead JT (1984) Removal of neuroblastoma cells from bone marrow with monoclonal antibodies conjugated to magnetic microspheres. Lancet 14: 70CrossRefGoogle Scholar
  22. 22.
    Favrot MC, Philip I, Combaret V, Maritaz O, Philip T (1987) Experimental evaluation of an immunomagnetic bone marrow purging procedure using the Burkitt lymphoma model. Bone Marrow Transplantation 2: 56–59Google Scholar
  23. 23.
    Combaret V, Favrot MC, Kremens B, Laurent JC, Philip I, Philip T (1987) Elimination of Burkitt cells from excess bone marrow with an immunomagnetic purging procedure. Selection of monoclonal antibodies is a critical step. In: Proceedings of the Third International Symposium on ABMT, Houston, pp 443–448Google Scholar
  24. 24.
    Reynolds PC, Seeger RC, Vo DD, Black AT, Wells J, Ugelstad J (1986) Model system for removing neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads. Cancer Res 46: 5882PubMedGoogle Scholar
  25. 25.
    Poynton CH, Dicke KA, Culbert S, Frankel LS, Jagannath S, Reading CL (1983) Immumomagnetic removal of CALLA positive cells from human bone marrow. Lancet 1: 524PubMedCrossRefGoogle Scholar
  26. 26.
    Berenson RJ, Bensinger WI, Kalamasz D, Martin P (1986) Elimination of Daudi lymphoblasts from human bone marrow using avidin-biotin immunoadsorption. Blood 67: 509PubMedGoogle Scholar
  27. 27.
    Filipovich AH, Vallera DA, Youle RJ, Quinones RR, Neville DM, Kersey JH (1984) Ex-vivo treatment of donor bone marrow with anti-T cell immunotoxins for prevention of graft-versushost disease. Lancet 1: 469PubMedCrossRefGoogle Scholar
  28. 28.
    Casellas P, Canat X, Fauser AA, Gros O, Laurent G, Poncelet P, Jansen FK (1985) Optimal elimination of leukemic T cells from human bone marrow with T101-ricin A chain immunotoxin. Blood 65: 289PubMedGoogle Scholar
  29. 29.
    Stong RC, Youle RJ, Vallera DA (1984) Elimination of clonogenic T-leukemic cells from human bone marrow using anti-Mr 65,000 protein immunotoxins. Cancer Res 44: 3000PubMedGoogle Scholar
  30. 30.
    Myers CD, Thorpe PE, Ross WCJ, Cumber AJ, Katz FE, Tax W, Greaves MF (1984) An immunotoxin with therapeutic potential in T cell leukemia: WT1-Ricin A. Blood 63: 1178PubMedGoogle Scholar
  31. 31.
    Muirhead M, Martin PJ, Torok-Storb B, Uhr JW, Vitetta ES (1983) Use of an antibody-ricin A-chain conjugate to delete neoplastic B cells from human bone marrow. Blood 62: 327PubMedGoogle Scholar
  32. 32.
    Coombes RC, Buckman R, Forster JA, Shepherd V, O’Hare MJ, Vincent M, Powles TJ, Neville AM (1986) In vitro and in vivo effects of a monoclonal antibody-toxin conjugate for use in autologous bone marrow transplantation for patients with breast cancer. Cancer Res 46: 4217PubMedGoogle Scholar
  33. 33.
    Uckun FM, Ramakrishnan S, Houston LL (1985) Increased efficiency in selective elimination of leukemia cells by a combination of stable derivative of cyclophosphamide and a human B-cellspecific immunotoxin containing pokeweed antiviral protein. Cancer Res 45: 69PubMedGoogle Scholar
  34. 34.
    Ramakrishnan S, Houston LL (1984) Inhibition of human acute lymphoblastic leukemia cells by immunotoxins: potentiation by chloroquine. Science 223: 58PubMedCrossRefGoogle Scholar
  35. 35.
    Bjorn MJ, Groetsema G, Scalapino L (1986) Antibody-pseudomonas exotoxin A conjugates cytotoxic to human breast cancer cells in vitro. Cancer Res 46: 3262PubMedGoogle Scholar
  36. 36.
    Janossy G, Prentice HG, Grob JP, Ivory K, Tidman N, Grundy J, Favrot M, Brenner MK, Campana D, Blacklock HA, Gilmore MJML, Patterson J, Griffiths PD, Hoffbrand AV (1986) T lymphocyte regeneration after transplantation of T cell depleted allogeneic bone marrow. Clin Exp Immunol 63: 577PubMedGoogle Scholar
  37. 37.
    Fischer A, Griscelli C, Blanche S, Le Deist F, Veber F, Lopez M, Delaage M, Olive D, Mawas C, Janossy G (1986) Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA-mismatched bonemarrow transplantation. Lancet 2: 1058PubMedCrossRefGoogle Scholar
  38. 38.
    Thierfelder S, Rodt H, Netzel B (1977) Transplantation of syngeneic bone marrow incubated with leucocyte antibodies. Transplantation 23: 459PubMedCrossRefGoogle Scholar
  39. 39.
    Hagenbeek A, Van Bekkum DW (eds) (1977) Proceedings of an International Workshop on comparative evaluation of the L5222 and the BNML rat leukemia models and their relevance for human acute leukemia. Leuk Res 1: 75–78Google Scholar
  40. 40.
    Reynolds CP, Black AT, Woody JN (1986) Sensitive method for detecting viable cells seeded into bone marrow. Cancer Res 46: 5878PubMedGoogle Scholar
  41. 41.
    Philip I, Favrot MC, Philip T (1987) Use of a liquid cell culture assay to quantify the elimination of Burkitt lymphoma cells from the bone marrow. J Immunol Methods 97: 11PubMedCrossRefGoogle Scholar
  42. 42.
    Ajani JA, Spitzer G, Tomasovic B, Drewinko B, Hug VM, Dicke K (1986) In vitro cytotoxicity patterns of standard and investigational agents on human bone marrow granulocyte-macrophage progenitor cells. Br J Cancer 54: 607PubMedCrossRefGoogle Scholar
  43. 43.
    Uckun FM, Gajil-Peczalska KJ, Kersey JH, Houston LL, Vallera DA (1986) Use of a novel colony assay to evaluate the cytotoxicity of an immunotoxin containing pokeweed antiviral protein against blast progenitor cells freshly obtained from patients with common B-lineage acute lymphoblastic leukemia. J Exp Med 163: 347PubMedCrossRefGoogle Scholar
  44. 44.
    Campana D, Janossy G (1986) Leukemia diagnosis and testing of complement fixing antibodies for bone marrow purging in acute lymphoid leukemia. Blood 68: 1264–1271PubMedGoogle Scholar
  45. 45.
    Moss TJ, Seeger RC, Kindler-Rohrborn A, Marangos PJ, Rajevsky MF, Reynolds CP (1985) Immunohistologic detection and phenotyping of neuroblastoma cells in bone marrow using cytoplasmic neuron specific enolase and cell surface antigens. In: Evans AE, d’Angio O, Seeger RC (eds) Advances in neuroblastoma research. Alan R Liss, New York, p 367Google Scholar
  46. 46.
    Philip I, Philip T, Favrot MC, Vuillaume M, Fontanière B, Chamard D, Lenoir GM (1984) Establisment of lymphomatous cell lines from bone marrow samples from patients with Burkitt’s lymphoma. JNCI 73: 835PubMedGoogle Scholar
  47. 47.
    Philip I, Favrot MC, Combaret V, Laurent JC, Kremens B, Philip T (1986) Use of a liquid cell culture assay to measure the in vitro elimination of Burkitt’s cells from the BM in preclinical and clinical procedures. In: Proceedings of the Third International Symposium on ABMT, Houston, pp 351–358Google Scholar
  48. 48.
    Philip T, Bernard JL, Zucker JM, Pinkerton R, Lutz P, Bordigoni P, Plouvier E, Robert A, Carton R, Philippe N, Philip I, Favrot MC (1987) High dose chemotherapy with bone marrow transplantation as consolidation treatment in neuroblastoma: an unselected group of stage IV patients over one year of age. J Clin Oncol 5: 266PubMedGoogle Scholar
  49. 49.
    De Fabriitis P, Bregni M, Lipton J, Greenberger J, Nadler L, Rothstein L, Korbling M, Ritz J, Bast RC (1985) Elimination of clonogenic Burkitt’s lymphoma cells from human bone marrow using 4-hydroperoxycyclophosphamide in combination with monoclonal antibodies and cornplement. Blood 5: 1064Google Scholar
  50. 50.
    Lebien TW, Anderson JM, Vallera DA, Uckun FM (1986) Increased efficacy in selection elimination of leukemic cell line clonogenic cells by a combination of monoclonal antibodies BA-1, BA-2, BA-3 plus complement and mafosfamid (ASTA Z 7557). Leuk Res 10: 139PubMedCrossRefGoogle Scholar
  51. 51.
    Favrot MC, Philip I, Poncelet P, Combaret V, Kremens B, Janossy G, Philip T (1987) Comparative efficiency of an immunomagnetic procedure and a rabbit complement lysis for eliminating BL cells from the bone marrow. In: Proceedings of the Third International symposium on ABMT, Houston, pp 359–364Google Scholar
  52. 52.
    Chang J, Coutinho L, Morgenstein G, Scarffe JH, Deakin D, Harrison C, Testa NG, Dexter TM (1986) Reconstitution of haemopoietic system with autologous marrow taken during relapse of acute myeloblastic leukaemia and grown in long-term culture. Lancet 1: 294PubMedCrossRefGoogle Scholar
  53. 53.
    Berenoson RJ, Andrews RG, Bensinger WI, Kalamasz D, Knitter G, Bernstein ID (1986) In vivo reconstitution of hematopoiesis in baboons using 12.8 positive marrow cells isolated by avidin-biotin immunoadsorption (Abstr 1025). Blood 68: 287Google Scholar
  54. 54.
    To LB, Haylock DN, Kimber RJ, Juttner CA (1984) High levels of circulating haematopoiesis stem cells in very early remission from acute non-lymphoblastic leukaemia and their collection and cryopreservation. Br J Haematol 58: 399PubMedCrossRefGoogle Scholar
  55. 55.
    Rosenberg SA, Lotze MT, Muul LM, Leituran S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp GA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313: 1485PubMedCrossRefGoogle Scholar
  56. 56.
    O’Reilly RJ, Kernan N, Collins N, Brochstein J, Cunningham I, Castro-Malaspina H, Laver J, Emanuel D, Gulati S, Flomenberg N, Keever C (1986) Abrogation of both acute and chronic GVHD following transplants of lectin agglutinated, E-rosette depleted (SBA-E-) marrow for leukemia (Abstr 1041). Blood 68: 291Google Scholar
  57. 57.
    Prentice HG, Janossy G, Price-Jones L, Tregdosiewicz LK, Panjwani DI, Graphokos S, Ivory K, Blacklock HA, Gilmore MJ, Tidman N, Skeggs DBL, Ball S, Patterson J, Hoffbrand AV (1984) Depletion of T-lymphocytes in donor marrow prevents significant graft versus host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet 1: 472PubMedCrossRefGoogle Scholar
  58. 58.
    Martin PJ, Hansen JA, Buckner CD, Sanders JE, Deeg HJ, Stewart P, Appelbaum FR, Clift R, Fefer A, Witherspoon RP, Kennedy MS, Sullivan KM, Flournoy N, Storb R, Thomas ED (1985) Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 66: 664PubMedGoogle Scholar
  59. 59.
    Hervé P, Cahn JY, Flesch M, Plouvier E, Racadot E, Noir A, Couteret Y, Goldstein G, Bernard A, Lenys R, Bresson JL, Leconte des Floris R, Peters (1987) Successful GVHD prevention without graft failure in 32 HLA-identical allogeneic bone marrow transplantations with marrow depleted of T-cells by monoclonal antibodies and complement. Blood 69: 388–393Google Scholar
  60. 60.
    Racadot E, Hervé P, Beaujean F, Vernant JP, Flesch M, Plouvier E, Andreu G, Rio B, Philippe N, Souillet G, Pico J, Bordigoni J, Ifrah N, Paitre ML, Lutz P, Morizet J, Bernard A (1986) Prevention of graft versus host disease in HLA matched bone marrow transplantation for malignant diseases. A multicentric study of 62 patients using 3 pan-T monoclonal antibodies and rabbit complement. J Clin Oncol 5: 426–435Google Scholar
  61. 61.
    Quinones RR, Youle RJ, Kersey JH, Zanjani ED, Azemove SM, Soderling CCB, Lebien TW, Beverley PCL, Neville DM, Vallera DA (1984) Anti-T cell monoclonal antibodies conjugated to ricin as potential reagents for human GVHD prophylaxis: effect on the generation of cytotoxic T cells in both peritoneal blood and bone marrow. J Immunol 132: 1322Google Scholar
  62. 62.
    Kemshead JT, Heath L, Gibson FM, Katz F, Richmond F, Treleaven J, Ugelstad J (1986) Magnetic microspheres and monoclonal antibodies for the depletion of neuroblastoma cells from bone marrow: experiences, improvements and observations. Br J Cancer 54: 771PubMedCrossRefGoogle Scholar
  63. 63.
    Seeger RC, Wells J, Lenarsky C, Feig SA, Selch M, Moss TJ, Ugelstad J, Reynolds CP (1986) Bone marrow transplantation for poor prognosis neuroblastoma (Abstr 20). J Cell Biochem 10D: 215Google Scholar
  64. 64.
    Douay L, Gorin NC, Laporte JP, Lopez M, Najman A, Duhamel G (1984) ASTA Z 7557 ( INN mafosfamide) for the in vitro treatment of human leukemic bone marrows. Invest New Drugs 2: 187PubMedCrossRefGoogle Scholar
  65. 65.
    Bast RC Jr, Sallan SE, Reynolds C, Lipton J, Ritz J (1985) Autologous bone marrow transplantation for CALLA-positive acute lymphoblastic leukemia: an update. In: Dicke KA, Spitzer G, Zander AR (eds) Autologous bone marrow transplantation. ND Anderson Hospital, Houston, pp 3–6Google Scholar
  66. 66.
    Ramsay N, Lebien TW, Nesbit M, McGlave P, Weisdorf D, Kenyon P, Hurd D, Goldman A, Kim T, Kersey (1985) Autologous bone marrow transplantation for patients with acute lymphoblastic leukemia in second or subsequent remission. Results of bone marrow treated with monoclonal antibodies BA-1, BA-2 and BA-3 plus complement. Blood 66: 508PubMedGoogle Scholar
  67. 67.
    Nadler LM, Takvorian T, Botnick L, Bast RC, Finberg R, Hellman S, Canellos GP, Schlossman SF (1984) Anti-B1 monoclonal antibody and complement treatment in autologous bone marrow transplantation for relapsed B-cell non-Hodgkin’s lymphoma. Lancet 2: 427PubMedCrossRefGoogle Scholar
  68. 68.
    Philip T, Biron P, Philip I, Favrot M, Souillet G, Frazppaz D, Jaubert J, Bordigoni P, Bernard JL, Laporte JP, Le Mevel A, Plouvier E, Marguerite G, Pinkerton R, Brizard CP, Freycon F, Forster HK, Philippe N, Brunat-Mentigny M (1986) Massive therapy and autologous bone marrow transplantation in pediatric and young adults Burkitt’s lymphoma (30 courses in 28 patients: a 5-year experience). Eur J Cancer Clin Oncol 22: 1015PubMedCrossRefGoogle Scholar
  69. 69.
    Baumgartner C, Brun del Re G, Forster HK, Bucher U, Delaveu B, Hirt A, Imbach P, Luthy A, Stern AC, Wagner HP (1985) Autologous bone marrow transplantation for pediatric non-Hodgkin’s lymphoma: in vitro purging of the graft with anti-Y29/55 monoclonal antibody and complement. In: Dicke KA, Spitzer G, Zander AR (eds) Autologous bone marrow transplantation. ND Anderson Hospital, Houston, pp 377–381Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. C. Favrot
  • T. Philip

There are no affiliations available

Personalised recommendations