Advertisement

Recent Advances in Hematopoietic Stem Cell Transplantation and Perspectives of RNAi Applications

  • Yngvar Fløisand
  • Mouldy Sioud
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 629)

Abstract

In adults, the bone marrow compartment contains hematopoietic stem cells (HSCs) which can differentiate into progenitors with more restricted lineage potential and generate all cellular elements of the blood. HSCs for stem cell transplantation can be obtained by bone marrow collection, mobilization into peripheral blood followed by apheresis, or use of stem cells from cord blood. Currently, hematopoietic stem cell transplantation (SCT) is used to treat patients with various hematological diseases. Although substantial progress has been made, a number of challenges can limit the efficacy of HSC transplantation, including the occurrence of graft-versus-host disease (GvHD) in allogeneic stem cell transplantation (ASCT), the susceptibility of patients to opportunistic infections and relapse of malignancies after SCT. Recent studies indicate that small interfering RNAs (siRNAs) can specifically and efficiently interfere with the expression of oncogenic genes. Therefore, the possibility of interfering with the expression of these proteins in hematopoietic cells may offer a new option to correct cell differentiation and function. In addition to the generation of T cells restricted by nonself MHC as reviewed by Stauss and colleagues in 1999, the modulation of NK cell receptor expression and T-cell activation is a new strategy that could limit GvHD. This chapter reviews the recent advances in ASCT and discusses the potential application of RNAi in hematopoietic cells.

Key words

Hematopoietic stem cells graft-versus-host disease NK cells RNA interference oncogenes 

References

  1. 1.
    Civin, C.I., Strauss, L.C., Brovall, C., Fackler, M.J., Schwartz, J.F., and Shaper, J.H. (1984) Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol, 133, 157–165.PubMedGoogle Scholar
  2. 2.
    Egeland, T., Tjonnfjord, G., Steen, R., Gaudernack, G., and Thorsby, E. (1993) Positive selection of bone marrow-derived CD34 positive cells for possible stem cell transplantation. Transplant Proc, 25, 1261–1263.PubMedGoogle Scholar
  3. 3.
    Gratwohl, A., Baldomero, H., Schwendener, A., Rocha, V., Apperley, J., Frauendorfer, K., and Niederwieser, D. (2009) The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies. Bone Marrow Transplant, 43, 275–291.PubMedCrossRefGoogle Scholar
  4. 4.
    Uzunel, M., Remberger, M., Sairafi, D., Hassan, Z., Mattsson, J., Omazic, B., Barkholt, L., and Ringden, O. (2006) Unrelated versus related allogeneic stem cell transplantation after reduced intensity conditioning. Transplantation, 82, 913–919.PubMedCrossRefGoogle Scholar
  5. 5.
    Remberger, M., Mattsson, J., Hausenberger, D., Schaffer, M., Svahn, B.M., and Ringden, O. (2008) Genomic tissue typing and optimal antithymocyte globuline dose using unrelated donors results in similar survival and relapse as HLA-identical siblings in haematopoietic stem-cell transplantation for leukaemia. Eur J Haematol, 80, 419–428.PubMedCrossRefGoogle Scholar
  6. 6.
    Heldal, D., Brinch, L., Tjonnfjord, G., Solheim, B.G., Egeland, T., Albrechtsen, D., Aamodt, G., and Evensen, S.A. (2003) Fewer relapses and increased chronic GVHD in patients transplanted with blood stem cells: a 5-year follow-up in a single centre study. Bone Marrow Transplant, 32, 257–264.PubMedCrossRefGoogle Scholar
  7. 7.
    Ballen, K.K., Spitzer, T.R., Yeap, B.Y., McAfee, S., Dey, B.R., Attar, E., Haspel, R., Kao, G., Liney, D., Alyea, E., Lee, S., Cutler, C., Ho, V., Soiffer, R., and Antin, J.H. (2007) Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Biol Blood Marrow Transplant, 13, 82–89.PubMedCrossRefGoogle Scholar
  8. 8.
    Ballen, K.K. (2005) New trends in umbilical cord blood transplantation. Blood, 105, 3786–3792.PubMedCrossRefGoogle Scholar
  9. 9.
    Barker, J.N., Weisdorf, D.J., DeFor, T.E., Blazar, B.R., McGlave, P.B., Miller, J.S., Verfaillie, C.M., and Wagner, J.E. (2005) Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood, 105, 1343–1347.PubMedCrossRefGoogle Scholar
  10. 10.
    Tomizawa, D., Aoki, Y., Nagasawa, M., Morio, T., Kajiwara, M., Sekine, T., Shimizu, N., Kato, M., Yachie, A., and Mizutani, S. (2005) Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome. Eur J Haematol, 75, 441–444.PubMedCrossRefGoogle Scholar
  11. 11.
    Dreger, P., Corradini, P., Kimby, E., Michallet, M., Milligan, D., Schetelig, J., Wiktor-Jedrzejczak, W., Niederwieser, D., Hallek, M., and Montserrat, E. (2007) Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia, 21, 12–17.PubMedCrossRefGoogle Scholar
  12. 12.
    Sorror, M.L., Storer, B.E., Sandmaier, B.M., Maris, M., Shizuru, J., Maziarz, R., Agura, E., Chauncey, T.R., Pulsipher, M.A., McSweeney, P.A., Wade, J.C., Bruno, B., Langston, A., Radich, J., Niederwieser, D., Blume, K.G., Storb, R., and Maloney, D.G. (2008) Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol, 26, 4912–4920.PubMedCrossRefGoogle Scholar
  13. 13.
    Dreger, P., Brand, R., Hansz, J., Milligan, D., Corradini, P., Finke, J., Deliliers, G.L., Martino, R., Russell, N., Van Biezen, A., Michallet, M., and Niederwieser, D. (2003) Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning. Leukemia, 17, 841–848.PubMedCrossRefGoogle Scholar
  14. 14.
    Khouri, I.F., Saliba, R.M., Giralt, S.A., Lee, M.S., Okoroji, G.J., Hagemeister, F.B., Korbling, M., Younes, A., Ippoliti, C., Gajewski, J.L., McLaughlin, P., Anderlini, P., Donato, M.L., Cabanillas, F.F., and Champlin, R.E. (2001) Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood, 98, 3595–3599.PubMedCrossRefGoogle Scholar
  15. 15.
    Vigouroux, S., Michallet, M., Porcher, R., Attal, M., Ades, L., Bernard, M., Blaise, D., Tabrizi, R., Garban, F., Cassuto, J.P., Chevalier, P., Facon, T., Ifrah, N., Renaud, M., Tilly, H., Vernant, J.P., Kuentz, M., Bourhis, J.H., Bordigoni, P., Deconinck, E., Lioure, B., Socie, G., and Milpied, N. (2007) Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: a survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC). Haematologica, 92, 627–634.PubMedCrossRefGoogle Scholar
  16. 16.
    Rezvani, A.R., Storer, B., Maris, M., Sorror, M.L., Agura, E., Maziarz, R.T., Wade, J.C., Chauncey, T., Forman, S.J., Lange, T., Shizuru, J., Langston, A., Pulsipher, M.A., Sandmaier, B.M., Storb, R., and Maloney, D.G. (2008) Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin’s lymphoma. J Clin Oncol, 26, 211–217.PubMedCrossRefGoogle Scholar
  17. 17.
    Robinson, S.P., Goldstone, A.H., Mackinnon, S., Carella, A., Russell, N., de Elvira, C.R., Taghipour, G., and Schmitz, N. (2002) Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood, 100, 4310–4316.PubMedCrossRefGoogle Scholar
  18. 18.
    Niscola, P., Romani, C., Cupelli, L., Scaramucci, L., Tendas, A., Dentamaro, T., Amadori, S., and de Fabritiis, P. (2007) Mucositis in patients with hematologic malignancies: an overview. Haematologica, 92, 222–231.PubMedCrossRefGoogle Scholar
  19. 19.
    Goldberg, J., Jacobsohn, D.A., Zahurak, M.L., and Vogelsang, G.B. (2005) Gastrointestinal toxicity from the preparative regimen is associated with an increased risk of graft-versus-host disease. Biol Blood Marrow Transplant, 11, 101–107.PubMedCrossRefGoogle Scholar
  20. 20.
    Stiff, P.J., Emmanouilides, C., Bensinger, W.I., Gentile, T., Blazar, B., Shea, T.C., Lu, J., Isitt, J., Cesano, A., and Spielberger, R. (2006) Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J Clin Oncol, 24, 5186–5193.PubMedCrossRefGoogle Scholar
  21. 21.
    Spielberger, R., Stiff, P., Bensinger, W., Gentile, T., Weisdorf, D., Kewalramani, T., Shea, T., Yanovich, S., Hansen, K., Noga, S., McCarty, J., LeMaistre, C.F., Sung, E.C., Blazar, B.R., Elhardt, D., Chen, M.G., and Emmanouilides, C. (2004) Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med, 351, 2590–2598.PubMedCrossRefGoogle Scholar
  22. 22.
    Filipovich, A.H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J.R., Lee, S.J., Martin, P., Chien, J., Przepiorka, D., Couriel, D., Cowen, E.W., Dinndorf, P., Farrell, A., Hartzman, R., Henslee-Downey, J., Jacobsohn, D., McDonald, G., Mittleman, B., Rizzo, J.D., Robinson, M., Schubert, M., Schultz, K., Shulman, H., Turner, M., Vogelsang, G., and Flowers, M.E. (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant, 11, 945–956.Google Scholar
  23. 23.
    Markey, K.A., MacDonald, K.P., and Hill, G.R. (2008) Impact of cytokine gene polymorphisms on graft-vs-host disease. Tissue Antigens, 72, 507–516.PubMedCrossRefGoogle Scholar
  24. 24.
    Rocha, V., Franco, R.F., Porcher, R., Bittencourt, H., Silva, W.A. Jr., Latouche, A., Devergie, A., Esperou, H., Ribaud, P., Socie, G., Zago, M.A., and Gluckman, E. (2002) Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. Blood, 100, 3908–3918.PubMedCrossRefGoogle Scholar
  25. 25.
    Holler, E., Rogler, G., Brenmoehl, J., Hahn, J., Greinix, H., Dickinson, A.M., Socie, G., Wolff, D., Finke, J., Fischer, G., Jackson, G., Rocha, V., Hilgendorf, I., Eissner, G., Marienhagen, J., and Andreesen, R. (2008) The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation. Int J Immunogenet, 35, 381–384.PubMedCrossRefGoogle Scholar
  26. 26.
    Dickinson, A.M., Middleton, P.G., Rocha, V., Gluckman, E., and Holler, E. (2004) Genetic polymorphisms predicting the outcome of bone marrow transplants. Br J Haematol, 127, 479–490.PubMedCrossRefGoogle Scholar
  27. 27.
    Mayor, N.P., Shaw, B.E., Hughes, D.A., Maldonado-Torres, H., Madrigal, J.A., Keshav, S., and Marsh, S.G. (2007) Single nucleotide polymorphisms in the NOD2/CARD15 gene are associated with an increased risk of relapse and death for patients with acute leukemia after hematopoietic stem-cell transplantation with unrelated donors. J Clin Oncol, 25, 4262–4269.PubMedCrossRefGoogle Scholar
  28. 28.
    Elmaagacli, A.H., Koldehoff, M., Hindahl, H., Steckel, N.K., Trenschel, R., Peceny, R., Ottinger, H., Rath, P.M., Ross, R.S., Roggendorf, M., Grosse-Wilde, H., and Beelen, D.W. (2006) Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes influence the risk for severe acute graft-versus-host disease in patients who underwent an allogeneic transplantation. Transplantation, 81, 247–254.PubMedCrossRefGoogle Scholar
  29. 29.
    Sioud, M. and Floisand, Y. (2009) NOD2/CARD15 on bone marrow CD34+ hematopoietic cells mediates induction of cytokines and cell differentiation. J Leukoc Biol, 85, 939–946.PubMedCrossRefGoogle Scholar
  30. 30.
    Ferrara, J.L., Levine, J.E., Reddy, P., and Holler, E. (2009) Graft-versus-host disease. Lancet, 373, 1550–1561.PubMedCrossRefGoogle Scholar
  31. 31.
    Graca, L., Thompson, S., Lin, C.Y., Adams, E., Cobbold, S.P., and Waldmann, H. (2002) Both CD4(+)CD25(+) and CD4(+)CD25(–) regulatory cells mediate dominant transplantation tolerance. J Immunol, 168, 5558–5565.PubMedGoogle Scholar
  32. 32.
    Hara, M., Kingsley, C.I., Niimi, M., Read, S., Turvey, S.E., Bushell, A.R., Morris, P.J., Powrie, F., and Wood, K.J. (2001) IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J Immunol, 166, 3789–3796.PubMedGoogle Scholar
  33. 33.
    Maul, J., Loddenkemper, C., Mundt, P., Berg, E., Giese, T., Stallmach, A., Zeitz, M., and Duchmann, R. (2005) Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology, 128, 1868–1878.PubMedCrossRefGoogle Scholar
  34. 34.
    Rieger, K., Loddenkemper, C., Maul, J., Fietz, T., Wolff, D., Terpe, H., Steiner, B., Berg, E., Miehlke, S., Bornhauser, M., Schneider, T., Zeitz, M., Stein, H., Thiel, E., Duchmann, R., and Uharek, L. (2006) Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood, 107, 1717–1723.PubMedCrossRefGoogle Scholar
  35. 35.
    Bolwell, B., Sobecks, R., Pohlman, B., Andresen, S., Rybicki, L., Kuczkowski, E., and Kalaycio, M. (2004) A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant, 34, 621–625.PubMedCrossRefGoogle Scholar
  36. 36.
    Baron, F., Little, M.T., and Storb, R. (2005) Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning. Blood Rev, 19, 153–164.PubMedCrossRefGoogle Scholar
  37. 37.
    Cutler, C., Stevenson, K., Kim, H.T., Richardson, P., Ho, V.T., Linden, E., Revta, C., Ebert, R., Warren, D., Choi, S., Koreth, J., Armand, P., Alyea, E., Carter, S., Horowitz, M., Antin, J.H., and Soiffer, R. (2008) Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood, 112, 4425–4431.PubMedCrossRefGoogle Scholar
  38. 38.
    Perfetti, P., Carlier, P., Strada, P., Gualandi, F., Occhini, D., Van Lint, M.T., Ibatici, A., Lamparelli, T., Bruno, B., Raiola, A.M., Dominietto, A., Di Grazia, C., Bregante, S., Zia, S., Ferrari, G.M., Stura, P., Pogliani, E., and Bacigalupo, A. (2008) Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD. Bone Marrow Transplant, 42, 609–617.PubMedCrossRefGoogle Scholar
  39. 39.
    Apisarnthanarax, N., Donato, M., Korbling, M., Couriel, D., Gajewski, J., Giralt, S., Khouri, I., Hosing, C., Champlin, R., Duvic, M., and Anderlini, P. (2003) Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results. Bone Marrow Transplant, 31, 459–465.PubMedCrossRefGoogle Scholar
  40. 40.
    Greinix, H.T., Knobler, R.M., Worel, N., Schneider, B., Schneeberger, A., Hoecker, P., Mitterbauer, M., Rabitsch, W., Schulenburg, A., and Kalhs, P. (2006) The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica, 91, 405–408.PubMedGoogle Scholar
  41. 41.
    Couriel, D., Saliba, R., Hicks, K., Ippoliti, C., de Lima, M., Hosing, C., Khouri, I., Andersson, B., Gajewski, J., Donato, M., Anderlini, P., Kontoyiannis, D.P., Cohen, A., Martin, T., Giralt, S., and Champlin, R. (2004) Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood, 104, 649–654.PubMedCrossRefGoogle Scholar
  42. 42.
    Van Lint, M.T., Milone, G., Leotta, S., Uderzo, C., Scime, R., Dallorso, S., Locasciulli, A., Guidi, S., Mordini, N., Sica, S., Cudillo, L., Fagioli, F., Selleri, C., Bruno, B., Arcese, W., and Bacigalupo, A. (2006) Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood, 107, 4177–4181.PubMedCrossRefGoogle Scholar
  43. 43.
    Berger, M., Biasin, E., Saglio, F., and Fagioli, F. (2008) Innovative approaches to treat steroid-resistant or steroid refractory GVHD. Bone Marrow Transplant, 42(Suppl 2), S101–S105.PubMedCrossRefGoogle Scholar
  44. 44.
    Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M.E., Remberger, M., Dini, G., Egeler, R.M., Bacigalupo, A., Fibbe, W., and Ringden, O. (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet, 371, 1579–1586.PubMedCrossRefGoogle Scholar
  45. 45.
    Neofytos, D., Horn, D., Anaissie, E., Steinbach, W., Olyaei, A., Fishman, J., Pfaller, M., Chang, C., Webster, K., and Marr, K. (2009) Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis, 48, 265–273.PubMedCrossRefGoogle Scholar
  46. 46.
    Maertens, J., Meersseman, W., and Van Bleyenbergh, P. (2009) New therapies for fungal pneumonia. Curr Opin Infect Dis, 22, 183–190.PubMedCrossRefGoogle Scholar
  47. 47.
    Hebart, H. and Einsele, H. (2004) Clinical aspects of CMV infection after stem cell transplantation. Hum Immunol, 65, 432–436.PubMedCrossRefGoogle Scholar
  48. 48.
    Haque, T., Wilkie, G.M., Taylor, C., Amlot, P.L., Murad, P., Iley, A., Dombagoda, D., Britton, K.M., Swerdlow, A.J., and Crawford, D.H. (2002) Treatment of Epstein–Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. Lancet, 360, 436–442.PubMedCrossRefGoogle Scholar
  49. 49.
    Haque, T., Wilkie, G.M., Jones, M.M., Higgins, C.D., Urquhart, G., Wingate, P., Burns, D., McAulay, K., Turner, M., Bellamy, C., Amlot, P.L., Kelly, D., MacGilchrist, A., Gandhi, M.K., Swerdlow, A.J., and Crawford, D.H. (2007) Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood, 110, 1123–1131.PubMedCrossRefGoogle Scholar
  50. 50.
    Mackinnon, S., Thomson, K., Verfuerth, S., Peggs, K., and Lowdell, M. (2008) Adoptive cellular therapy for cytomegalovirus infection following allogeneic stem cell transplantation using virus-specific T cells. Blood Cells Mol Dis, 40, 63–67.PubMedCrossRefGoogle Scholar
  51. 51.
    Einsele, H., Kapp, M., and Grigoleit, G.U. (2008) CMV-specific T cell therapy. Blood Cells Mol Dis, 40, 71–75.PubMedCrossRefGoogle Scholar
  52. 52.
    Hogan, W.J. and Deeg, H.J. (2005) Stem cell transplantation: graft-mediated antileukemia effects. Methods Mol Med, 109, 421–444.PubMedGoogle Scholar
  53. 53.
    Weiden, P.L., Flournoy, N., Thomas, E.D., Prentice, R., Fefer, A., Buckner, C.D., and Storb, R. (1979) Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med, 300, 1068–1073.PubMedCrossRefGoogle Scholar
  54. 54.
    Weiden, P.L., Sullivan, K.M., Flournoy, N., Storb, R., and Thomas, E.D. (1981) Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med, 304, 1529–1533.PubMedCrossRefGoogle Scholar
  55. 55.
    Ringden, O., Labopin, M., Gluckman, E., Reiffers, J., Vernant, J.P., Jouet, J.P., Harousseau, J.L., Fiere, D., Bacigalupo, A., Frassoni, F., and Gorin, N.C. (1997) Strong antileukemic effect of chronic graft-versus-host disease in allogeneic marrow transplant recipients having acute leukemia treated with methotrexate and cyclosporine. The Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Transplant Proc, 29, 733–734.PubMedCrossRefGoogle Scholar
  56. 56.
    Horowitz, M.M., Gale, R.P., Sondel, P.M., Goldman, J.M., Kersey, J., Kolb, H.J., Rimm, A.A., Ringden, O., Rozman, C., Speck, B. et al. (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood, 75, 555–562.PubMedGoogle Scholar
  57. 57.
    Kolb, H.J., Schattenberg, A., Goldman, J.M., Hertenstein, B., Jacobsen, N., Arcese, W., Ljungman, P., Ferrant, A., Verdonck, L., Niederwieser, D., van Rhee, F., Mittermueller, J., de Witte, T., Holler, E., and Ansari, H. (1995) Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood, 86, 2041–2050.PubMedGoogle Scholar
  58. 58.
    Bacigalupo, A., Soracco, M., Vassallo, F., Abate, M., Van Lint, M.T., Gualandi, F., Lamparelli, T., Occhini, D., Mordini, N., Bregante, S., Figari, O., Benvenuto, F., Sessarego, M., Fugazza, G., Carlier, P., and Valbonesi, M. (1997) Donor lymphocyte infusions (DLI) in patients with chronic myeloid leukemia following allogeneic bone marrow transplantation. Bone Marrow Transplant, 19, 927–932.PubMedCrossRefGoogle Scholar
  59. 59.
    Guglielmi, C., Arcese, W., Dazzi, F., Brand, R., Bunjes, D., Verdonck, L.F., Schattenberg, A., Kolb, H.J., Ljungman, P., Devergie, A., Bacigalupo, A., Gomez, M., Michallet, M., Elmaagacli, A., Gratwohl, A., Apperley, J., and Niederwieser, D. (2002) Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood, 100, 397–405.PubMedCrossRefGoogle Scholar
  60. 60.
    Soiffer, R.J., Alyea, E.P., Hochberg, E., Wu, C., Canning, C., Parikh, B., Zahrieh, D., Webb, I., Antin, J., and Ritz, J. (2002) Randomized trial of CD8+ T-cell depletion in the prevention of graft-versus-host disease associated with donor lymphocyte infusion. Biol Blood Marrow Transplant, 8, 625–632.PubMedCrossRefGoogle Scholar
  61. 61.
    Baron, F., Siquet, J., Schaaf-Lafontaine, N., Baudoux, E., Hermanne, J.P., Fillet, G., and Beguin, Y. (2002) Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation. Haematologica, 87, 78–88.PubMedGoogle Scholar
  62. 62.
    Ciceri, F., Bonini, C., Gallo-Stampino, C., and Bordignon, C. (2005) Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation. Cytotherapy, 7, 144–149.PubMedCrossRefGoogle Scholar
  63. 63.
    Stauss, H.J. (1999) Immunotherapy with CTLs restricted by nonself MHC. Immunol Today, 20, 180–183.PubMedCrossRefGoogle Scholar
  64. 64.
    Bae, J., Martinson, J.A., and Klingemann, H.G. (2005) Identification of CD19 and CD20 peptides for induction of antigen-specific CTLs against B-cell malignancies. Clin Cancer Res, 11, 1629–1638.PubMedCrossRefGoogle Scholar
  65. 65.
    Moris, A., Teichgraber, V., Gauthier, L., Buhring, H.J., and Rammensee, H.G. (2001) Cutting edge: characterization of allorestricted and peptide-selective alloreactive T cells using HLA-tetramer selection. J Immunol, 166, 4818–4821.PubMedGoogle Scholar
  66. 66.
    Bae, J., Martinson, J.A., and Klingemann, H.G. (2004) Identification of novel CD33 antigen-specific peptides for the generation of cytotoxic T lymphocytes against acute myeloid leukemia. Cell Immunol, 227, 38–50.PubMedCrossRefGoogle Scholar
  67. 67.
    Amrolia, P.J., Reid, S.D., Gao, L., Schultheis, B., Dotti, G., Brenner, M.K., Melo, J.V., Goldman, J.M., and Stauss, H.J. (2003) Allorestricted cytotoxic T cells specific for human CD45 show potent antileukemic activity. Blood, 101, 1007–1014.PubMedCrossRefGoogle Scholar
  68. 68.
    Gao, L., Yang, T.H., Tourdot, S., Sadovnikova, E., Hasserjian, R., and Stauss, H.J. (1999) Allo-major histocompatibility complex-restricted cytotoxic T lymphocytes engraft in bone marrow transplant recipients without causing graft-versus-host disease. Blood, 94, 2999–3006.PubMedGoogle Scholar
  69. 69.
    Heemskerk, M.H., Hoogeboom, M., de Paus, R.A., Kester, M.G., van der Hoorn, M.A., Goulmy, E., Willemze, R., and Falkenburg, J.H. (2003) Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region. Blood, 102, 3530–3540.PubMedCrossRefGoogle Scholar
  70. 70.
    Ljunggren, H.G. and Karre, K. (1990) In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today, 11, 237–244.PubMedCrossRefGoogle Scholar
  71. 71.
    Moretta, L., Ciccone, E., Moretta, A., Hoglund, P., Ohlen, C., and Karre, K. (1992) Allorecognition by NK cells: nonself or no self?. Immunol Today, 13, 300–306.PubMedCrossRefGoogle Scholar
  72. 72.
    Ruggeri, L., Mancusi, A., Burchielli, E., Capanni, M., Carotti, A., Aloisi, T., Aversa, F., Martelli, M.F., and Velardi, A. (2008) NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. Blood Cells Mol Dis, 40, 84–90.PubMedCrossRefGoogle Scholar
  73. 73.
    Ruggeri, L., Capanni, M., Urbani, E., Perruccio, K., Shlomchik, W.D., Tosti, A., Posati, S., Rogaia, D., Frassoni, F., Aversa, F., Martelli, M.F., and Velardi, A. (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science, 295, 2097–2100.PubMedCrossRefGoogle Scholar
  74. 74.
    Dodero, A., Carniti, C., Raganato, A., Vendramin, A., Farina, L., Spina, F., Carlo-Stella, C., Di Terlizzi, S., Milanesi, M., Longoni, P., Gandola, L., Lombardo, C., and Corradini, P. (2009) Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery. Blood, 113, 4771–4779.PubMedCrossRefGoogle Scholar
  75. 75.
    Schaffer, M., Malmberg, K.J., Ringden, O., Ljunggren, H.G., and Remberger, M. (2004) Increased infection-related mortality in KIR-ligand-mismatched unrelated allogeneic hematopoietic stem-cell transplantation. Transplantation, 78, 1081–1085.PubMedCrossRefGoogle Scholar
  76. 76.
    Lee, G.K., Park, H.J., Macleod, M., Chandler, P., Munn, D.H., and Mellor, A.L. (2002) Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology, 107, 452–460.PubMedCrossRefGoogle Scholar
  77. 77.
    Munn, D.H. and Mellor, A.L. (2004) IDO and tolerance to tumors. Trends Mol Med, 10, 15–18.PubMedCrossRefGoogle Scholar
  78. 78.
    Munn, D.H., Zhou, M., Attwood, J.T., Bondarev, I., Conway, S.J., Marshall, B., Brown, C., and Mellor, A.L. (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science, 281, 1191–1193.PubMedCrossRefGoogle Scholar
  79. 79.
    Mellor, A.L. and Munn, D.H. (2001) Tryptophan catabolism prevents maternal T cells from activating lethal anti-fetal immune responses. J Reprod Immunol, 52, 5–13.PubMedCrossRefGoogle Scholar
  80. 80.
    Munn, D.H., Sharma, M.D., Hou, D., Baban, B., Lee, J.R., Antonia, S.J., Messina, J.L., Chandler, P., Koni, P.A., and Mellor, A.L. (2004) Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest, 114, 280–290.PubMedGoogle Scholar
  81. 81.
    Munn, D.H. and Mellor, A.L. (2006) The tumor-draining lymph node as an immune-privileged site. Immunol Rev, 213(1), 146–158.PubMedCrossRefGoogle Scholar
  82. 82.
    Jasperson, L.K., Bucher, C., Panoskaltsis-Mortari, A., Taylor, P.A., Mellor, A.L., Munn, D.H., and Blazar, B.R. (2008) Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality. Blood, 111, 3257–3265.PubMedCrossRefGoogle Scholar
  83. 83.
    Steckel, N.K., Kuhn, U., Beelen, D.W., and Elmaagacli, A.H. (2003) Indoleamine 2,3-dioxygenase expression in patients with acute graft-versus-host disease after allogeneic stem cell transplantation and in pregnant women: association with the induction of allogeneic immune tolerance? Scand J Immunol, 57, 185–191.PubMedCrossRefGoogle Scholar
  84. 84.
    Aiuti, A., Slavin, S., Aker, M., Ficara, F., Deola, S., Mortellaro, A., Morecki, S., Andolfi, G., Tabucchi, A., Carlucci, F., Marinello, E., Cattaneo, F., Vai, S., Servida, P., Miniero, R., Roncarolo, M.G., and Bordignon, C. (2002) Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science, 296, 2410–2413.PubMedCrossRefGoogle Scholar
  85. 85.
    Aiuti, A., Brigida, I., Ferrua, F., Cappelli, B., Chiesa, R., Marktel, S., and Roncarolo, M.G. (2009) Hematopoietic stem cell gene therapy for adenosine deaminase deficient-SCID. Immunol Res, 44, 150–159.PubMedCrossRefGoogle Scholar
  86. 86.
    Aiuti, A., Cattaneo, F., Galimberti, S., Benninghoff, U., Cassani, B., Callegaro, L., Scaramuzza, S., Andolfi, G., Mirolo, M., Brigida, I., Tabucchi, A., Carlucci, F., Eibl, M., Aker, M., Slavin, S., Al-Mousa, H., Al Ghonaium, A., Ferster, A., Duppenthaler, A., Notarangelo, L., Wintergerst, U., Buckley, R.H., Bregni, M., Marktel, S., Valsecchi, M.G., Rossi, P., Ciceri, F., Miniero, R., Bordignon, C., and Roncarolo, M.G. (2009) Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med, 360, 447–458.PubMedCrossRefGoogle Scholar
  87. 87.
    Santilli, G., Thornhill, S.I., Kinnon, C., and Thrasher, A.J. (2008) Gene therapy of inherited immunodeficiencies. Expert Opin Biol Ther, 8, 397–407.PubMedCrossRefGoogle Scholar
  88. 88.
    Howe, S.J., Mansour, M.R., Schwarzwaelder, K., Bartholomae, C., Hubank, M., Kempski, H., Brugman, M.H., Pike-Overzet, K., Chatters, S.J., de Ridder, D., Gilmour, K.C., Adams, S., Thornhill, S.I., Parsley, K.L., Staal, F.J., Gale, R.E., Linch, D.C., Bayford, J., Brown, L., Quaye, M., Kinnon, C., Ancliff, P., Webb, D.K., Schmidt, M., von Kalle, C., Gaspar, H.B., and Thrasher, A.J. (2008) Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest, 118, 3143–3150.PubMedCrossRefGoogle Scholar
  89. 89.
    Goldman, J.M. and Melo, J.V. (2003) Chronic myeloid leukemia – advances in biology and new approaches to treatment. N Engl J Med, 349, 1451–1464.PubMedCrossRefGoogle Scholar
  90. 90.
    Martinez, N., Drescher, B., Riehle, H., Cullmann, C., Vornlocher, H.P., Ganser, A., Heil, G., Nordheim, A., Krauter, J., and Heidenreich, O. (2004) The oncogenic fusion protein RUNX1-CBFA2T1 supports proliferation and inhibits senescence in t(8;21)-positive leukaemic cells. BMC Cancer, 4, 44.PubMedCrossRefGoogle Scholar
  91. 91.
    Heidenreich, O., Krauter, J., Riehle, H., Hadwiger, P., John, M., Heil, G., Vornlocher, H.P., and Nordheim, A. (2003) AML1/MTG8 oncogene suppression by small interfering RNAs supports myeloid differentiation of t(8;21)-positive leukemic cells. Blood, 101, 3157–3163.PubMedCrossRefGoogle Scholar
  92. 92.
    Scherr, M., Battmer, K., Winkler, T., Heidenreich, O., Ganser, A., and Eder, M. (2003) Specific inhibition of bcr-abl gene expression by small interfering RNA. Blood, 101, 1566–1569.PubMedCrossRefGoogle Scholar
  93. 93.
    Robbins, M.A., Li, M., Leung, I., Li, H., Boyer, D.V., Song, Y., Behlke, M.A., and Rossi, J.J. (2006) Stable expression of shRNAs in human CD34+ progenitor cells can avoid induction of interferon responses to siRNAs in vitro. Nat Biotechnol, 24, 566–571.PubMedCrossRefGoogle Scholar
  94. 94.
    Parham, P. (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol, 5, 201–214.PubMedCrossRefGoogle Scholar
  95. 95.
    Ruggeri, L., Mancusi, A., Burchielli, E., Aversa, F., Martelli, M.F., and Velardi, A. (2007) Natural killer cell alloreactivity in allogeneic hematopoietic transplantation. Curr Opin Oncol, 19, 142–147.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Yngvar Fløisand
    • 1
  • Mouldy Sioud
    • 2
  1. 1.Department of HematologyRikshopitalet–Radiumhospitalet, University HospitalOsloNorway
  2. 2.Department of ImmunologyInstitute for Cancer Research, Rikshospitalet-Radiumhospitalet, University HospitalOsloNorway

Personalised recommendations