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Viral purging of haematological autografts: should we sneeze on the graft?

Bone Marrow Transplantation volume 40, pages 1–12 (2007)Cite this article

Abstract

High-dose cytotoxic chemotherapy followed by autologous haematopoietic stem cell transplantation (ASCT) is extensively used for the treatment of many haematopoietic, as well as several epithelial cancers. Disease relapse may be the result of tumour contamination within autograft as evidenced by gene marking studies. The multiple purging strategies that have been described to date have not proven effective in most ASCT settings. This review addresses the possibility of using oncolytic viruses as a novel purging strategy. DNA viruses such as genetically engineered adenoviral vectors have widely been used to deliver either a prodrug-activating enzyme or express wild-type p53 selectively in tumour cells in ex vivo purging protocols. In addition, conditionally replicating adenoviruses that selectively replicate in tumour cells and herpes simplex virus type 1 are other DNA viruses that have been tested as ex vivo purging agents under laboratory conditions. Vesicular stomatitis virus (VSV) and reovirus are naturally occurring RNA viruses that appear to hold promise as purging agents under ex vivo and in vivo settings. Preclinical data demonstrate reovirus's purging potential against breast, monocytic and myeloma cell lines as well as patient-derived tumours of diffuse large B-cell lymphoma, chronic lymphocytic leukaemia, Waldenstrom macroglobulinemia and small lymphocytic lymphoma. In addition, VSV has shown effective killing of leukaemic cell lines and multiple myeloma patient specimens. Given the increasing interest in the utilization of viruses as purging agents, the following review provides a timely summary of the potential and the challenges of oncolytic viruses as purging modalities during ASCT.

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References

  1. Armitage JO . Bone marrow transplantation in the treatment of patients with lymphoma. Blood 1989; 73: 1749–1758.

    CAS  PubMed  Google Scholar 

  2. Freedman AS, Takvorian T, Anderson KC, Mauch P, Rabinowe SN, Blake K et al. Autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse. J Clin Oncol 1990; 8: 784–791.

    CAS  PubMed  Google Scholar 

  3. Ball ED, Mills LE, Cornwell III GG, Davis BH, Coughlin CT, Howell AL et al. Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow. Blood 1990; 75: 1199–1206.

    CAS  PubMed  Google Scholar 

  4. Gribben JG, Linch DC, Singer CR, McMillan AK, Jarrett M, Goldstone AH . Successful treatment of refractory Hodgkin's disease by high-dose combination chemotherapy and autologous bone marrow transplantation. Blood 1989; 73: 340–344.

    CAS  PubMed  Google Scholar 

  5. Wallerstein Jr R, Spitzer G, Dunphy F, Huan S, Hortobagyi G, Yau J et al. A phase II study of mitoxantrone, etoposide, and thiotepa with autologous marrow support for patients with relapsed breast cancer. J Clin Oncol 1990; 8: 1782–1788.

    PubMed  Google Scholar 

  6. Eapen M . Report on state of the art in blood and marrow transplantation – the IBMTR/ABMTR summary slide with guide. Int Bone Marrow Transplant Registry Autologous Blood Marrow Transplant Registry 2002; 9: 1–11.

    Google Scholar 

  7. Gratwohl A, Passweg J, Baldomero H, Urbano-Ispizua A . Hematopoietic stem cell transplantation activity in Europe 1999. Bone Marrow Transplant 2001; 27: 899–916.

    CAS  PubMed  Google Scholar 

  8. Gratwohl A, Baldomero H, Schmid O, Horisberger B, Bargetzi M, Urbano-Ispizua A . Change in stem cell source for hematopoietic stem cell transplantation (HSCT) in Europe: a report of the EBMT activity survey 2003. Bone Marrow Transplant 2005; 36: 575–590.

    CAS  PubMed  Google Scholar 

  9. Horowitz MM, Loberiza FR, Bredeson CN, Rizzo JD, Nugent ML . Transplant registries: guiding clinical decisions and improving outcomes. Oncology (Williston Park) 2001; 15: 649–659.

    CAS  Google Scholar 

  10. Goldman JM, Horowitz MM . The international bone marrow transplant registry. Int J Hematol 2002; 76 (Suppl 1): 393–397.

    PubMed  Google Scholar 

  11. Alvarnas JC, Forman SJ . Graft purging in autologous bone marrow transplantation: a promise not quite fulfilled. Oncology (Williston Park) 2004; 18: 867–876.

    Google Scholar 

  12. Vogel W, Kopp HG, Kanz L, Einsele H . Myeloma cell contamination of peripheral blood stem-cell grafts can predict the outcome in multiple myeloma patients after high-dose chemotherapy and autologous stem-cell transplantation. J Cancer Res Clin Oncol 2005; 131: 214–218.

    PubMed  Google Scholar 

  13. Galimberti S, Morabito F, Guerrini F, Palumbo GA, Azzara A, Martino M et al. Peripheral blood stem cell contamination evaluated by a highly sensitive molecular method fails to predict outcome of autotransplanted multiple myeloma patients. Br J Haematol 2003; 120: 405–412.

    PubMed  Google Scholar 

  14. Barbui AM, Galli M, Dotti G, Belli N, Borleri G, Gritti G et al. Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma. Br J Haematol 2002; 116: 202–210.

    PubMed  Google Scholar 

  15. Friedberg JW, Kim H, Li S, Neuberg D, Boyd K, Daley H et al. Ex vivo B cell depletion using the Eligix B Cell SC system and autologous peripheral blood stem cell transplantation in patients with follicular non-Hodgkin's lymphoma. Bone Marrow Transplant 2003; 32: 681–686.

    CAS  PubMed  Google Scholar 

  16. De RL, Lalle M, Pandolfi A, Ruscio C, Amodeo R . Autologous bone marrow transplantation with negative immunomagnetic purging for aggressive B-cell non-Hodgkin's lymphoma in first complete remission. Ann Hematol 2002; 81: 575–581.

    Google Scholar 

  17. Galimberti S, Marasca R, Caracciolo F, Fazzi R, Papineschi F, Benedetti E et al. The role of molecular monitoring in autotransplantation for non-Hodgkin's lymphoma. Bone Marrow Transplant 2002; 29: 581–587.

    CAS  PubMed  Google Scholar 

  18. McCann JC, Kanteti R, Shilepsky B, Miller KB, Sweet M, Schenkein DP . High degree of occult tumor contamination in bone marrow and peripheral blood stem cells of patients undergoing autologous transplantation for non-Hodgkin's lymphoma. Biol Blood Marrow Transplant 1996; 2: 37–43.

    CAS  PubMed  Google Scholar 

  19. Feller N, van der Pol MA, Waaijman T, Weijers GW, Westra G, Ossenkoppele GJ et al. Immunologic purging of autologous peripheral blood stem cell products based on CD34 and CD133 expression can be effectively and safely applied in half of the acute myeloid leukemia patients. Clin Cancer Res 2005; 11: 4793–4801.

    CAS  PubMed  Google Scholar 

  20. Feller N, Jansen-van der Weide MC, van der Pol MA, Westra GA, Ossenkoppele GJ, Schuurhuis GJ . Purging of peripheral blood stem cell transplants in AML: a predictive model based on minimal residual disease burden. Exp Hematol 2005; 33: 120–130.

    PubMed  Google Scholar 

  21. Miyamoto T, Nagafuji K, Harada M, Eto T, Fujisaki T, Kubota A et al. Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia. Br J Haematol 1995; 91: 132–138.

    CAS  PubMed  Google Scholar 

  22. Sandler ES, Homans A, Mandell L, Amylon M, Wall DA, Devidas M et al. Hematopoietic stem cell transplantation after first marrow relapse of non-T, non-B acute lymphoblastic leukemia: a pediatric oncology group pilot feasibility study. J Pediatr Hematol Oncol 2006; 28: 210–215.

    PubMed  Google Scholar 

  23. Atta J, Fauth F, Keyser M, Petershofen E, Weber C, Lippok G et al. Purging in BCR-ABL-positive acute lymphoblastic leukemia using immunomagnetic beads: comparison of residual leukemia and purging efficiency in bone marrow vs peripheral blood stem cells by semiquantitative polymerase chain reaction. Bone Marrow Transplant 2000; 25: 97–104.

    CAS  PubMed  Google Scholar 

  24. Leung W, Chen AR, Klann RC, Moss TJ, Davis JM, Noga SJ et al. Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma. Bone Marrow Transplant 1998; 22: 971–979.

    CAS  PubMed  Google Scholar 

  25. Burchill SA, Kinsey SE, Picton S, Roberts P, Pinkerton CR, Selby P et al. Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma. Med Pediatr Oncol 2001; 36: 213–219.

    CAS  PubMed  Google Scholar 

  26. Schulze R, Schulze M, Wischnik A, Ehnle S, Doukas K, Behr W et al. Tumor cell contamination of peripheral blood stem cell transplants and bone marrow in high-risk breast cancer patients. Bone Marrow Transplant 1997; 19: 1223–1228.

    CAS  PubMed  Google Scholar 

  27. Vannucchi AM, Bosi A, Glinz S, Pacini P, Linari S, Saccardi R et al. Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT-PCR for cytokeratin-19 mRNA. Br J Haematol 1998; 103: 610–617.

    CAS  PubMed  Google Scholar 

  28. Bokemeyer C, Gillis AJ, Pompe K, Mayer F, Metzner B, Schleucher N et al. Clinical impact of germ cell tumor cells in apheresis products of patients receiving high-dose chemotherapy. J Clin Oncol 2001; 19: 3029–3036.

    CAS  PubMed  Google Scholar 

  29. Kasahara T, Hara N, Bilim V, Tomita Y, Saito K, Obara K et al. Sequential detection of alphafetoprotein-bearing cells in blood stem cell fraction of germ cell tumour patients. Br J Cancer 2001; 85: 1119–1123.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Brenner MK, Rill DR, Moen RC, Krance RA, Mirro Jr J, Anderson WF et al. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet 1993; 341: 85–86.

    CAS  PubMed  Google Scholar 

  31. Deisseroth AB, Zu Z, Claxton D, Hanania EG, Fu S, Ellerson D et al. Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML. Blood 1994; 83: 3068–3076.

    CAS  PubMed  Google Scholar 

  32. Rill DR, Santana VM, Roberts WM, Nilson T, Bowman LC, Krance RA et al. Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells. Blood 1994; 84: 380–383.

    CAS  PubMed  Google Scholar 

  33. Shimoni A, Korbling M . Tumor cell contamination in re-infused stem cell autografts: does it have clinical significance? Crit Rev Oncol Hematol 2002; 41: 241–250.

    PubMed  Google Scholar 

  34. Bierman PJ, Sweetenham JW, Loberiza Jr FR, Taghipour G, Lazarus HM, Rizzo JD et al. Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma: a comparison with allogeneic and autologous transplantation – The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. J Clin Oncol 2003; 21: 3744–3753.

    PubMed  Google Scholar 

  35. Gorin NC, Aegerter P, Auvert B, Meloni G, Goldstone AH, Burnett A et al. Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging. Blood 1990; 75: 1606–1614.

    CAS  PubMed  Google Scholar 

  36. Gribben JG, Freedman AS, Neuberg D, Roy DC, Blake KW, Woo SD et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med 1991; 325: 1525–1533.

    CAS  PubMed  Google Scholar 

  37. Sharp JG, Kessinger A, Mann S, Crouse DA, Armitage JO, Bierman P et al. Outcome of high-dose therapy and autologous transplantation in non-Hodgkin's lymphoma based on the presence of tumor in the marrow or infused hematopoietic harvest. J Clin Oncol 1996; 14: 214–219.

    CAS  PubMed  Google Scholar 

  38. Spyridonidis A, Schmidt M, Bernhardt W, Papadimitriou A, Azemar M, Wels W et al. Purging of mammary carcinoma cells during ex vivo culture of CD34+ hematopoietic progenitor cells with recombinant immunotoxins. Blood 1998; 91: 1820–1827.

    CAS  PubMed  Google Scholar 

  39. Ball ED, Wilson J, Phelps V, Neudorf S . Autologous bone marrow transplantation for acute myeloid leukemia in remission or first relapse using monoclonal antibody-purged marrow: results of phase II studies with long-term follow-up. Bone Marrow Transplant 2000; 25: 823–829.

    CAS  PubMed  Google Scholar 

  40. Lemoli RM, Gasparetto C, Scheinberg DA, Moore MA, Clarkson BD, Gulati SC . Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination. Blood 1991; 77: 1829–1836.

    CAS  PubMed  Google Scholar 

  41. Martin-Henao GA, Picon M, Amill B, Querol S, Gonzalez JR, Martinez C et al. Isolation of CD34+ progenitor cells from peripheral blood by use of an automated immunomagnetic selection system: factors affecting the results. Transfusion 2000; 40: 35–43.

    CAS  PubMed  Google Scholar 

  42. van Heeckeren WJ, Vollweiler J, Fu P, Cooper BW, Meyerson H, Lazarus HM et al. Randomised comparison of two B-cell purging protocols for patients with B-cell non-Hodgkin lymphoma: in vivo purging with rituximab versus ex vivo purging with CliniMACS CD34 cell enrichment device. Br J Haematol 2006; 132: 42–55.

    PubMed  Google Scholar 

  43. Casorati G, Locatelli F, Pagani S, Garavaglia C, Montini E, Lisini D et al. Bone marrow-resident memory T cells survive pretransplant chemotherapy and contribute to early immune reconstitution of patients with acute myeloid leukemia given mafosfamide-purged autologous bone marrow transplantation. Exp Hematol 2005; 33: 212–218.

    CAS  PubMed  Google Scholar 

  44. Tsujino I, Anderson GS, Sieber F . Postirradiation hyperthermia selectively potentiates the merocyanine 540-sensitized photoinactivation of small cell lung cancer cells. Photochem Photobiol 2001; 73: 191–198.

    CAS  PubMed  Google Scholar 

  45. Brasseur N, Menard I, Forget A, el Jastimi R, Hamel R, Molfino NA et al. Eradication of multiple myeloma and breast cancer cells by TH9402-mediated photodynamic therapy: implication for clinical ex vivo purging of autologous stem cell transplants. Photochem Photobiol 2000; 72: 780–787.

    CAS  PubMed  Google Scholar 

  46. Keir M, Fiddes R, Biggs JC, Kearney PP . Sensitivity of c-erbB positive cells to a ligand toxin and its utility in purging breast cancer cells from peripheral blood stem cell (PBSC) collections. Stem Cells 2000; 18: 422–427.

    CAS  PubMed  Google Scholar 

  47. LaCasse EC, Bray MR, Patterson B, Lim WM, Perampalam S, Radvanyi LG et al. Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation. Blood 1999; 94: 2901–2910.

    CAS  PubMed  Google Scholar 

  48. Bensinger WI, Rowley S, Appelbaum FR . CD 34-selected allogeneic peripheral blood stem cell (PBSC) transplantation in older patients with advanced haematologic malignancies. Blood 1995; 86: 97a.

    Google Scholar 

  49. Bensinger WI . Should we purge? Bone Marrow Transplant 1998; 21: 113–115.

    CAS  PubMed  Google Scholar 

  50. Demirer T, Gooley T, Buckner CD, Petersen FB, Lilleby K, Rowley S et al. Influence of total nucleated cell dose from marrow harvests on outcome in patients with acute myelogenous leukemia undergoing autologous transplantation. Bone Marrow Transplant 1995; 15: 907–913.

    CAS  PubMed  Google Scholar 

  51. Gorin NC . High-dose therapy for acute myelocytic leukemia. In: Armitage JO AKH (ed). High-dose Cancer Therapy (Pharmacology, Hematopoietins, Stem Cells). Williams and Wilkins: Baltimore, MD, 1992, pp 569–606.

    Google Scholar 

  52. Aghi M, Martuza RL . Oncolytic viral therapies – the clinical experience. Oncogene 2005; 24: 7802–7816.

    CAS  PubMed  Google Scholar 

  53. Chen L, Pulsipher M, Chen D, Sieff C, Elias A, Fine HA et al. Selective transgene expression for detection and elimination of contaminating carcinoma cells in hematopoietic stem cell sources. J Clin Invest 1996; 98: 2539–2548.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Seth P, Brinkmann U, Schwartz GN, Katayose D, Gress R, Pastan I et al. Adenovirus-mediated gene transfer to human breast tumor cells: an approach for cancer gene therapy and bone marrow purging. Cancer Res 1996; 56: 1346–1351.

    CAS  PubMed  Google Scholar 

  55. Garcia-Sanchez F, Pizzorno G, Fu SQ, Nanakorn T, Krause DS, Liang J et al. Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a potential purging method for autologous transplantation. Blood 1998; 92: 672–682.

    CAS  PubMed  Google Scholar 

  56. Teoh G, Chen L, Urashima M, Tai YT, Celi LA, Chen D et al. Adenovirus vector-based purging of multiple myeloma cells. Blood 1998; 92: 4591–4601.

    CAS  PubMed  Google Scholar 

  57. Marini FC, Snell V, Yu Q, Zhang X, Singletary SE, Champlin R et al. Purging of contaminating breast cancer cells from hematopoietic stem cell grafts by adenoviral GAL-TEK gene therapy and magnetic antibody cell separation. Clin Cancer Res 1999; 5: 1557–1568.

    CAS  PubMed  Google Scholar 

  58. Hirai M, Kelsey LS, Vaillancourt M, Maneval DC, Watanabe T, Talmadge JE . Purging of human breast cancer cells from stem cell products with an adenovirus containing p53. Cancer Gene Ther 2000; 7: 197–206.

    CAS  PubMed  Google Scholar 

  59. Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N et al. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 2000; 6: 821–825.

    CAS  PubMed  Google Scholar 

  60. Meck MM, Wierdl M, Wagner LM, Burger RA, Guichard SM, Krull EJ et al. A virus-directed enzyme prodrug therapy approach to purging neuroblastoma cells from hematopoietic cells using adenovirus encoding rabbit carboxylesterase and CPT-11. Cancer Res 2001; 61: 5083–5089.

    CAS  PubMed  Google Scholar 

  61. Hirai M, LaFace D, Robinson S, Kelsey L, Johnson R, Wen SF et al. Ex vivo purging by adenoviral p53 gene therapy does not affect NOD-SCID repopulating activity of human CD34+ cells. Cancer Gene Ther 2001; 8: 936–947.

    CAS  PubMed  Google Scholar 

  62. Wu A, Mazumder A, Martuza RL, Liu X, Thein M, Meehan KR et al. Biological purging of breast cancer cells using an attenuated replication-competent herpes simplex virus in human hematopoietic stem cell transplantation. Cancer Res 2001; 61: 3009–3015.

    CAS  PubMed  Google Scholar 

  63. Adachi Y, Reynolds PN, Yamamoto M, Wang M, Takayama K, Matsubara S et al. A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. Cancer Res 2001; 61: 7882–7888.

    CAS  PubMed  Google Scholar 

  64. Lillo R, Ramirez M, Alvarez A, Santos S, Garcia-Castro J, Fernandez D et al. Efficient and nontoxic adenoviral purging method for autologous transplantation in breast cancer patients. Cancer Res 2002; 62: 5013–5018.

    CAS  PubMed  Google Scholar 

  65. Wagner LM, Guichard SM, Burger RA, Morton CL, Straign CM, Ashmun RA et al. Efficacy and toxicity of a virus-directed enzyme prodrug therapy purging method: preclinical assessment and application to bone marrow samples from neuroblastoma patients. Cancer Res 2002; 62: 5001–5007.

    CAS  PubMed  Google Scholar 

  66. Thirukkumaran CM, Luider JM, Stewart DA, Cheng T, Lupichuk SM, Nodwell MJ et al. Reovirus oncolysis as a novel purging strategy for autologous stem cell transplantation. Blood 2003; 102: 377–387.

    CAS  PubMed  Google Scholar 

  67. Lichty BD, Stojdl DF, Taylor RA, Miller L, Frenkel I, Atkins H et al. Vesicular stomatitis virus: a potential therapeutic virus for the treatment of hematologic malignancy. Hum Gene Ther 2004; 15: 821–831.

    CAS  PubMed  Google Scholar 

  68. Thirukkumaran CM, Luider JM, Stewart DA, Alain T, Russell JA, Auer IA et al. Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts. Bone Marrow Transplant 2005; 35: 1055–1064.

    CAS  PubMed  Google Scholar 

  69. Wroblewski JM, Lay LT, Meeker TC . Adenoviral vectors in hematology: purging, stem cell gene transfer, or both. Blood 1997; 89: 4664–4665.

    CAS  PubMed  Google Scholar 

  70. Hirai M, Kelsey LS, Maneval DC, Vaillancourt M, Talmadge JE . Adenovirus p53 purging for human breast cancer stem cell products. Acta Haematol 1999; 101: 97–105.

    CAS  PubMed  Google Scholar 

  71. Ozbun MA, Butel JS . Tumor suppressor p53 mutations and breast cancer: a critical analysis. Adv Cancer Res 1995; 66: 71–141.

    CAS  PubMed  Google Scholar 

  72. Katayose D, Gudas J, Nguyen H, Srivastava S, Cowan KH, Seth P . Cytotoxic effects of adenovirus-mediated wild-type p53 protein expression in normal and tumor mammary epithelial cells. Clin Cancer Res 1995; 1: 889–897.

    CAS  PubMed  Google Scholar 

  73. Harris MP, Sutjipto S, Wills KN, Hancock W, Cornell D, Johnson DE et al. Adenovirus-mediated p53 gene transfer inhibits growth of human tumor cells expressing mutant p53 protein. Cancer Gene Ther 1996; 3: 121–130.

    CAS  PubMed  Google Scholar 

  74. Vogan K, Bernstein M, Leclerc JM, Brisson L, Brossard J, Brodeur GM et al. Absence of p53 gene mutations in primary neuroblastomas. Cancer Res 1993; 53: 5269–5273.

    CAS  PubMed  Google Scholar 

  75. Dilber MS, Phelan A, Aints A, Mohamed AJ, Elliott G, Smith CI et al. Intercellular delivery of thymidine kinase prodrug activating enzyme by the herpes simplex virus protein, VP22. Gene Therapy 1999; 6: 12–21.

    CAS  PubMed  Google Scholar 

  76. Dietzschold B, Repprecht CE, Fu ZF, Koprowski H . Rhabdoviruses. In: Fields BN, Knipe DM, Howley PM (eds). Fields Virology. Lippincott-Raven: Philadelphia, PA, 1996, pp 341–346.

    Google Scholar 

  77. Fields BN, Hawkins K . Human infection with the virus of vesicular stomatitis during an epizootic. N Engl J Med 1967; 277: 989–994.

    CAS  PubMed  Google Scholar 

  78. Lichty BD, Power AT, Stojdl DF, Bell JC . Vesicular stomatitis virus: re-inventing the bullet. Trends Mol Med 2004; 10: 210–216.

    CAS  PubMed  Google Scholar 

  79. Tyler KL, Fields BN . Reoviruses. In: Fields BN, Knipe DM, Howley PM (eds). Fields Virology. Lippincott-Raven: Philadelphia, PA, 1996, pp 1597–1623.

    Google Scholar 

  80. Strong JE, Coffey MC, Tang D, Sabinin P, Lee PW . The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J 1998; 17: 3351–3362.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Norman KL, Lee PW . Not all viruses are bad guys: the case for reovirus in cancer therapy. Drug Discov Today 2005; 10: 847–855.

    CAS  PubMed  Google Scholar 

  82. Cooper BW, Moss TJ, Ross AA, Ybanez J, Lazarus HM . Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer. J Clin Oncol 1998; 16: 3509–3517.

    CAS  PubMed  Google Scholar 

  83. Carella AM, Lerma E, Corsetti MT, Dejana A, Basta P, Vassallo F et al. Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia. Blood 1999; 93: 1534–1539.

    CAS  PubMed  Google Scholar 

  84. Czuczman MS, Grillo-Lopez AJ, White CA, Saleh M, Gordon L, LoBuglio AF et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 1999; 17: 268–276.

    CAS  PubMed  Google Scholar 

  85. Czuczman MS, Grillo-Lopez AJ, McLaughlin P, White CA, Saleh M, Gordon L et al. Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy. Ann Oncol 2001; 12: 109–114.

    CAS  PubMed  Google Scholar 

  86. Bhatia R, SMLMT. Growth factor mobilized peripheral blood stem cell collections form CML patients in complete cytogenetic remission on imatinib mesylate (Gleevec) treatment are Ph− by standard criteria but are contaminated with bcr/abl+ progenitor cells. Blood 2002; 100: 109a.

    Google Scholar 

  87. Hirasawa K, Nishikawa SG, Norman KL, Coffey MC, Thompson BG, Yoon CS et al. Systemic reovirus therapy of metastatic cancer in immune-competent mice. Cancer Res 2003; 63: 348–353.

    CAS  PubMed  Google Scholar 

  88. Forsyth P, Roldan G, George C, Wallace C, Morris D, Cairncross J et al. A phase 1 trial of of intratumoural (i.t.) administration of reovirus in patients with histologically confirmed recurrent malignant gliomas (MGs). J Clin Oncol 2006; 24: 73S.

    Google Scholar 

  89. Vidal L, Pandha H, Spicer J, Harrington KJ, Allen S, Leader D et al. A phase I study of reolysin given intravenously to patients with advanced malignancies. J Clin Oncol 2006; 24: 136S.

    Google Scholar 

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  1. Department of Medicine, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada

    C M Thirukkumaran, J A Russell, D A Stewart & D G Morris

  2. Department of Medicine and Oncology, University of Calgary, Calgary, Alberta, Canada

    C M Thirukkumaran, J A Russell, D A Stewart & D G Morris

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Thirukkumaran, C., Russell, J., Stewart, D. et al. Viral purging of haematological autografts: should we sneeze on the graft?. Bone Marrow Transplant 40, 1–12 (2007). https://doi.org/10.1038/sj.bmt.1705668

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