Skip to main content
SpringerLink
Log in

Bone marrow transplantation using unrelated donors for haematological malignancies

  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Bone marrow transplantation from unrelated donors is increasingly used to treat haematological malignancies. There are almost 4 million volunteer donors now available. Therefore, it is possible to find an HLA-A, -B and -DR-identical donor for around 70% of the patients. The major obstacles to unrelated bone marrow transplantations have been rejection, severe acute graft-versus-host disease (GVHD) and prolonged immune recovery leading to frequent infections and a high transplant-related mortality. However, with improved tissue typing using DNA techniques, immunosuppression using T-cell depletionin vitro orin vivo, the frequency of acute GVHD is acceptable and the results approach those obtained with HLA-identical siblings. For patients with chronic myeloid leukaemia, the worldwide 3-year survival is around 40%. Other indications for bone marrow transplantation with unrelated marrow include acute leukaemia and myelodysplastic syndromes with high-risk features. Unrelated cord blood cells and unrelated peripheral blood progenitor cells will be increasingly used as alternative haematopoietic stem cell sources to bone marrow. Improved immunosuppression, more accurate tissue typing, growth factors and better management of infections is expected to improve outcome using unrelated haematopoietic stem cells for transplantation in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Thomas, E.D., Storb, R., Clift, R.A., Fefer, A., Johnson, F.L., Neiman, P.E., Lerner, K.G., Glucksberg, H. and Buckner, C.D. (1975) Bone marrow transplantation Parts I and ILN. Engl. J. Med. 292, 832–43, 895-902.

    PubMed  CAS  Google Scholar 

  2. Barrett, A.J., Horowitz, M.M. and Gale, R.P. (1989) Marrow-transplantation for acute lymphoblastic leukemia: Factors affecting relapse and survival.Blood 74, 862–71.

    PubMed  CAS  Google Scholar 

  3. Goldman, J.M., Gale, R.P., Horowitz, M.M., Biggs, J.C., Champlin, R.E., Gluckman, R.E., Hoffman, R.G., Jacobsen, S.J., Marmont, A.M., McGlave, P.B., Messner, H.A., Rimm, A.A., Rozman, C, Speck B., Tura, S., Weiner, R.S. and Bortin, M.M. (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk of relapse associated with T-cell depletion.Ann. Intern. Med. 108, 806–14.

    PubMed  CAS  Google Scholar 

  4. Ringden, O., Zwaan, F.E., Hermans, J. and Gratwohl, A. for the Leukemia Working party of the European Group for Bone Marrow Transplantation (1987) European experience of bone marrow transplantation for leukemia.Transplant Proc. 19, 2600–04.

    Google Scholar 

  5. Copelan, E.A. and McGuire, E.A. (1995) The biology and treatment of acute lymphoblastic leukemia in adults.Blood 85, 1151–68.

    PubMed  CAS  Google Scholar 

  6. Burnett, A.K. and Eden, O.B. (1997) The treatment of acute leukemia.Lancet 349, 270–5.

    Article  PubMed  CAS  Google Scholar 

  7. Appelbaum, F.R., Sullivan, K.M., Buckner, C.D., Clift, R.A., Deeg, HJ., Fefer, A., Hill, R., Mortimer, J., Neiman, P.E., Sanders, J.E.et al. (1987) Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation.J. Clin. Oncol. 5, 1340–7.

    PubMed  CAS  Google Scholar 

  8. Hansen, J.A., Clift, R.A., Thomas, E.D., Buckner, C.D., Storb, R. and Giblett, E.R. (1980) Transplantation of marrow from an unrelated donor to patient with acute leukaemia.N. Engl. J. Med. 303, 565–7.

    PubMed  CAS  Google Scholar 

  9. Beatty, P.G., Hansen, J.A., Longton, G.M., Thomas, E.D., Sander, J.E., Martin, P.J., Bearman, S.I., Anasetti, C., Petersdorf, E.W., Mickelson, E.M., Pepe, M.S., Appelbaum, F.R., Buckner, C.D., Clift, R.A., Peterson, F.B., Stewart, P.S., Storb, R.F., Sullivan, K.M., Tesler, M.C. and Witherspoon, R.P. (1991) Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies.Transplantation 51, 443–7.

    Article  PubMed  CAS  Google Scholar 

  10. Hows, J.M., Bradley, B.A., Gore, S., Downie, T., Howard, M. and Gluckman, E. on behalf of the International Marrow Unrelated Search and Transplant (IMUST) Study. (1993) Prospective evaluation of unrelated donor bone marrow transplantation.Bone Marrow Transplant 12, 371–392.

    Google Scholar 

  11. Marks, D.I., Cuffls, J.O., Ward, K.N., Lacey, S., Syzdlo, R., Hughes, T.P., Schwarer, A.P., Lutz, E., Barrett, A.J., Hows, J.M., Batchelor, R. and Goldman, J. (1993) Allogeneic bone marrow transplantation for chronic myeloid leukemia using sibling and volunteer unrelated donors. A comparison of complications in the first 2 years.Ann. Intent. Med. 119, 207–14.

    CAS  Google Scholar 

  12. Gale, R.P. and Horowitz, M.M. (1993) Alternative donor transplants for leukemia.Bone Marrow Transplant. 11 (suppl 1), 66–7.

    PubMed  Google Scholar 

  13. Atkinson, K., Dodds, AJ., Concannon, A.J., Milliken, S., Downs, K., Marshall, G., Wilson, F. and Staniforth, D. (1993) Unrelated volunteer bone marrow transplantation: initial experience at St Vincent’s Hospital, Sydney.Austral. N. Zeal. J. Med. 23, 450–7.

    CAS  Google Scholar 

  14. Trigg, M.E. (1993) Bone marrow transplantation using alternative donors. Mismatched related donors or closely matched unrelated donors.Am. J. Ped. Hematol. - Oncol. 15, 141–9.

    CAS  Google Scholar 

  15. Davies, S.M., Ramsay, N.K., Haake, R.J., Kersey, J.H., Weisdorf, D.J., McGlave, P.B. and Blazar, B.R (1994) Comparison of engraftment in recipients of matched sibling or unrelated donor marrow allografts.Bone Marrow Transplant. 13, 51–7.

    PubMed  CAS  Google Scholar 

  16. Ringdén, O., Remberger, M., Persson, U., Ljungman, P., Aldener, A., Andström, E., Aschan, J., Bolme, P., Dahllöf, G., Dalianis, T., Gahrton, G., Hägglund, H., Lönnqvist, B., Olerup, O., Shanwell, A., Sparrelid, E., Winiarski, J., Öberg, M. and Möller, E. (1995) Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with FiLA-identical siblings.Bone Marrow Transplant 15, 619–25.

    PubMed  Google Scholar 

  17. Ochs, L., Shu, X.O., Miller, J., Enright, H., Wagner, J., Filipovich, A., Miller, W. and Weisdorf, D. (1995) Late infections after allogeneic bone marrow transplantation: comparison of incidence in related and unrelated donor transplant recipients.Blood 86, 3979–86.

    PubMed  CAS  Google Scholar 

  18. Mattsson, J., Ringdén, O., Aschan, J., Barkholt, L., Dalianis, T., Hägglund, H., Ljungman, P., Lönnqvist, B., Tollemar, J., Winiarski, J. and Remberger, M. (1997) A low incidence of grades II to IV acute GVHD, but high mortality from infections using HLA-A, -B and -DR identical unrelated donors and immunosuppression with ATG, cyclosporine and methotrexate.Transplantation Proceedings, in press.

  19. Young Yan, S. (1987) A standardized method for detection of HLA-A and HLA-B alleles in one-dimensional isoelectric focusing (IEF) gel electrophoresis. In B Dupont (ed.)Immunology of HLA, p.332, New York, NY, Springer Verlag.

    Google Scholar 

  20. Carlsson, B., Wallin, J., Böhme, J. and Möller, E. (1987) HLA-DR-DQ haplotypes defined by restriction fragment analysis. Correlation to serology.Hum. Immunol. 20, 95–113.

    Article  PubMed  CAS  Google Scholar 

  21. Olerup, O. and Zetterquist, H. (1992) HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: An alternative to serological DR typing in clinical practise including donor-recipient matching in cadaveric transplantation.Tissue Antigens 39,225–35.

    PubMed  CAS  Google Scholar 

  22. Tiercy, J.-M., Morel, C, Freidel, A.C., Zwahlen, F., Gebuhrer, L., Bétuel, H., Jeannet, M. and Mach, B. (1991) Selection of unrelated donors for bone marrow transplantation is improved by HLA class II genotyping with oligonucleotide hybridization.Proc. Natl Acad. Sci. USA 88, 7121.

    Article  PubMed  CAS  Google Scholar 

  23. Nademanee, A., Schmidt, G.M., Parker, P., Dagis, A.C., Stein, A., Snyder, D.S., O’Donnell, M., Smith, E.P., Stepan, D.E., Molina, A., Wong, K.K., Margolin, K., Somlo, G., Littrell, B., Woo, D., Sniecinski, L, Niland, J.C and Forman, SJ. (1995) The outcome of matched unrelated donor marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate and prednisone.Blood 86, 1228–34.

    PubMed  CAS  Google Scholar 

  24. Speiser, D.E., Tiercy, J.-M., Rufer, N., Grundschober, C., Gratwohl, A., Chapuis, B., Helg, C, Löliger, C.-C, Siren, M.-K-., Roosned, E. and Jeannet, M. (1996) High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.Blood 87, 4455–62.

    PubMed  CAS  Google Scholar 

  25. Kernan, N.A., Bartsch, G., Ash, R.C., Beatty, P.G., Champlin, R., Filipovich, A., Gajewski, J., Hansen, J.A., Henslee-Downey, J., McGullough, J., McGlave, P., Perkins, H.A., Philips, G.L., Sanders, J., Stroncek, D., Thomas, E.D. and Blume, K.G. (1993) Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program.N. Engl. J. Med. 328, 593–602.

    Article  PubMed  CAS  Google Scholar 

  26. Beatty, P.G., Anasetti, C, Hansen, J.A., Longton, G.M., Sanders, J.E., Martin, P.J., Mickelson, E.M., Choo, S.Y., Petersdorf, E.W., Pepe, M.S., Appelbaum, F.R., Bearman, S.L, Buckner, CD., Clift, R.A., Petersen, F.B., Singer, J., Stewart, P.S., Storb, R.F., Sullivan, K.M., Tesler, M.C, Witherspoon, R.P. and Thomas, E.D. (1993) Marrow transplantation from unrelated donors for treatment of hematologie malignancies: effect of mismatching for one HLA locus.Blood 81, 249–53.

    PubMed  CAS  Google Scholar 

  27. Balduzzi, A., Gooley, T., Anasetti, C, Sanders, J.E., Martin, P.J., Petersdorf, E.W., Appelbaum, F.R., Buckner, CD., Matthews, D., Storb, R., Sullivan, K.M. and Hansen, J.A. (1995) Unrelated donor marrow transplantation in children.Blood 86, 3247–56.

    PubMed  CAS  Google Scholar 

  28. Petersdorf, E.W., Smith, A.G., Mickelson, E.M., Longton, G.M., Anasetti, C, Choo, S.Y., Martin, PJ. and Hansen, J.A. (1993) The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease following unrelated donor marrow transplantation.Blood 81, 1923–32.

    PubMed  CAS  Google Scholar 

  29. Petersdorf, E.W., Longton, G.M., Anasetti, C, Martin, P.J., Mickelson, E.M., Smith, A.G. and Hansen, J.A. (1995) The significance of HLA-DRB1 matching on clinical outcome after HLA-A, -B, -DR identical unrelated donor marrow transplantation.Blood 86, 1606–13.

    PubMed  CAS  Google Scholar 

  30. Davies, S.M., Shu, X.O., Blazar, B.R., Filipovich, A., Kersey, J.H., Krivit, W., McCullough, J., Miller, W.J., Ramsay, N.K.C, Segali, M., Wagner, J.E., Weisdorf, DJ. and McGlave, P.B. (1995) Unrelated donor bone marrow transplantation: Influence of HLA A and B incompatibility and outcome.Blood 86, 1636–42.

    PubMed  CAS  Google Scholar 

  31. Kaminski, E., Hows, J.M., Man, S., MacKinnon, S., Hughes, T.P. and Goldman, J.M. (1989) Prediction of graft versus host disease by frequency analysis of cytotoxic cells after unrelated donor transplantation.Transplantation 48, 608–13.

    PubMed  CAS  Google Scholar 

  32. Spencer, A., Szydio, R.M., Brookes, P.A., Kaminski, E., Rule, S., van Rhee, F., Ward, K.M., Hale, G., Waldman, H., Hows, J.M., Batchelor, J.R. and Goldman, J.M. (1995) Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: Major prognostic impact of HLA class I identity between donor and recipient.Blood 86, 3590–97.

    PubMed  CAS  Google Scholar 

  33. Klein, J.L., Avalos, B.R., Belt, P., Taylor, C.A., Ezzone, S.A., Scholl, M.D., Fisher, J., Young, D. and Copelan, E.A. (1996) Bone marrow engraftment following unrelated donor transplantation utilizing busulfan and cyclophosphamide preparatory chemotherapy.Bone Marrow Transplant. 17, 479–83.

    PubMed  CAS  Google Scholar 

  34. Metha, J., Powles, R.L., Mitchell, P., Rege, K., De Lord, C. and Treleaven, J. (1994) Graft failure after bone marrow transplantation from unrelated donors using busulfan and cyclophosphamide for conditioning.Bone Marrow Transplant. 13, 583–7.

    Google Scholar 

  35. Apperley, J.F., Jones, L., Hale, G., Waldmann, H., Hows, J., Rombos, Y., Tsatalas, C, Marcus, R.E., Goolden, A.W.G., Gordon-Smith, E., Catovsky, D., Dalton, D.A.G. and Goldman, J.M. (1986) Bone marrow transplantation for patients with chronic myeloid leukemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may interact the risk of leukemic relapse.Bone Marrow Transplant 1, 53–66.

    PubMed  CAS  Google Scholar 

  36. Willemze, R., Richel, DJ., Falkenburg, J.H., Hale, G., Waldman, H., Zwaan, F.E. and Fibbe, W.E. (1992)In vivo use of Campath-1G to prevent graft-versus-host disease and graft rejection after bone marrow transplantation.Bone Marrow Transplant,9, 255–61.

    PubMed  CAS  Google Scholar 

  37. Ringdén, O., Pihlstedt, P., Markling, L, Aschan, J., Båryd, L, Ljungman, P., Lönnqvist, B., Tollemar, J., Janossy, G. and Sundberg, B. (1991) Prevention of graft-versus-host disease with T cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients.Bone Marrow Transplant.7, 221–6.

    PubMed  Google Scholar 

  38. Marmont, A.M., Horowitz, M.M., Gale, R.P., Ash, R.C., van Bekkum, D.W., Champlin, R.E., Dicke, K.A., Goldman, J.M., Good, R.A., Herzig, R.H., Hong, R., Masaoka, T., O’Reilly, R.J., Prentice, H.G., Rimm, A.A., Ringdén, O., Speck, B., Weiner, R.S. and Bortin, M.M. (1990) T-cell depletion of HLA-identical transplants in leukemia.Blood 78, 2120–30.

    Google Scholar 

  39. Vartdal, F., Albrechtsen, D., Ringdén, O., Kvalheim, G., Lea, T., Bosnes, V., Gaudernack, G., Brinchmann, J. and Ugelstad, J. (1987) Immunomagnetic treatment of bone marrow allografts.Bone Marrow Transplant.2 (suppl 2), 94–8.

    Google Scholar 

  40. Storb, R., Deeg, H.J., Whitehead, J., Appelbaum, F., Beatty, P., Bensinger, W., Buckner, C.D., Clift, R., Doney, K., Farewell, V., Hansen, J., Hill, R., Lum, L., Martin, P., McGuffin, R., Sanders, J., Steward, P., Sullivan, K., Witherspoon, R. and Yee, G. (1986) Methotrexate and cyclosporin compared with cyclosporin alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia.N. Engl. J. Med. 314, 729–35.

    PubMed  CAS  Google Scholar 

  41. Ringdén, O., Horowitz, M.M., Sondel, P., Gale, R.P., Biggs, J.G., Champlin, R.E., Deeg, HJ., Dicke, K., Masoaka, T., Powles, R.L., Rimm, A.A., Rozman, C, Sobocinski, K.A., Speck, B., Zwaan, F.E. and Bortin, M.M. (1993) Methotrexate, cyclosporin or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia?Blood 81, 1094–101.

    PubMed  Google Scholar 

  42. Leelasiri, A., Greer, J.P., Stein, R.S., Goodman, S., Brandt, S.A., Edwards, J.R. and Wolff, S.N. (1995) Graft-versus-host-disease prophylaxis for matched unrelated donor bone marrow transplantation: comparison between cyclosporm-methotrexate and cyclosporin-methotrexate-methylprednisolone.Bone Marrow Transplant 15, 401–5.

    PubMed  CAS  Google Scholar 

  43. Phillips, G.L., Nevill, T.J., Spinelli, J.J., Nantel, S.H., Klmgemann, H.-G., Bamett, M.J., Shepherd, J.D., Chan, K-W., Meharchand, J.M., Sutherland, H.J., Reece, D.E. and Messner, H.A. (1995) Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantationBone Marrow Transplant. 15, 213–9.

    PubMed  CAS  Google Scholar 

  44. Wagner, J.E., Kernan, N.A., Steinbuch, M., Broxmeyer, H.E. and Gluckman, E. (1995) Allogeneic sibling umbilical cord-blood transplantation in children with malignant and non-malignant disease.Lancet 346, 214–9.

    Article  PubMed  CAS  Google Scholar 

  45. Sheridan, W.P., Begley, C.G., Juttner, C.A., Szer, J., Bik To, L., Maher, D., McGrath, K.M., Morstyn, G. and Fox, R.M. (1992) Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy.Lancet 339, 640–4.

    Article  PubMed  CAS  Google Scholar 

  46. Dreger, P., Suttorp, M., Haferlach, T., Loffler, H., Schmitz, N. and Schroyes, W. (1993) Allogeneic granulocyte colony-stimulating factor-mobilised peripheral blood progenitor cells for treatment of engraftment failure after bone marrow transplantation.Blood 81, 1404–7.

    PubMed  CAS  Google Scholar 

  47. Russel, N.H., Hunter, A., Rogers, S., Hartley, J. and Andersson, D. (1993) Peripheral blood stem cells as an alternative to marrow for allogeneic transplantation.Lancet 341, 1482.

    Article  Google Scholar 

  48. Ringdén, O. and Nilsson, B. (1985) Death by graft-versus-host disease associated with HLA mismatch, high recipient age, low marrow cell dose, and splenectomy.Transplantation 40, 39–44.

    PubMed  Google Scholar 

  49. Ringdén, O., Lönnqvist, B., Hägglund, H., Ljungman, P., Shanwell, A., Lawlor, E. and Schmitz, N. (1995) Transplantation with peripheral blood stem cells from unrelated donors without serious graft-versus-host disease.Bone Marrow Transplant.16, 856–7.

    PubMed  Google Scholar 

  50. Stockschläder, M., Löliger, C, Krüger, W., Zeller, W., Heyll, A., Schönrock-Nabulsi, P. and Zander, A. (1995) Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor.Bone Marrow Transplant 16, 719–22.

    PubMed  Google Scholar 

  51. Ringdén, O., Potter, M.N., Oakhill, A., Cornish, J., Hägglund, H., Lönnqvist, B., Shanwell, A., Winiarski, J. and Pamphilon, D.H. (1996) Transplantation of peripheral blood progenitor cells from unrelated donors.Bone Marrow Transplant 17 (suppl 2), 62–4.

    Google Scholar 

  52. Horowitz, M.M., for the International Bone Marrow Transplant Registry (IBMTR). (1996) Results of related and unrelated donor transplants for leukemia. In: Royal College of Physicians of Edinburgh. Consensus Conference of Unrelated Donor Bone Marrow Transplantation, p. 2.

  53. Potter, M.N. (1996) Unrelated donor bone marrow transplantation for acute leukaemia in adults: the UK experience. In: Royal College of Physicians of Edinburgh. Consensus Conference of Unrelated Donor Bone Marrow Transplantation, p. 3.

  54. Oakhill, A. (1996) Matched and mismatched unrelated donor bone marrow transplantation for childhood acute leukaemia: Bristol 1988–1996. In: Royal College of Physicians of Edinburgh. Consensus Conference of Unrelated Donor Bone Marrow Transplantation, p. 6.

  55. Casper, J., Camitta, B., Truirt, R., Baxter-Lowe, L.A., Bunin, N., Lawton, C, Murray, K., Hunter, J., Pietryga, D., Garbrecht, F., Keever Taylor, C, Drobyski, W., Horowitz, M., Flomenberg, N. and Ash, R. (1995) Unrelated marrow donor transplants for children with leukemia or myelodysplasia.Blood 85, 2354–63.

    PubMed  CAS  Google Scholar 

  56. Gale, R.P., Horowitz, M.M., Weiner, R.S., Ash, R., Atkinson, K., Babu, R., Dicke, K., Klein, J., Lowenberg, B., Reiffers, J., Rimm, A., Rowlings, P., Sandberg, A., Sobocinski, K., Veum-Stone, J. and Bortin, M. (1995) Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myelogenous leukemia in first remission.Bone Marrow Transplant 16, 203–8.

    PubMed  CAS  Google Scholar 

  57. Ringdén, O., Labopin, M., Gluckman, E., Hows, J.M., Bradley, B.A., Fouillard, L., Jacobsen, N., Vernant, J.P., Boogaerts, M., Witz, F., Harousseau, L.J. and Gorin, N.C. For the Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation (EBMT) and the International Marrow Unrelated Search and Transplant (IMUST) study. (1997) Donor search or autografting in patients with acute leukaemia who lack an HLA-identical sibling? A matched-pair analysis.Bone Marrow Transplant, in press.

  58. Saarinen, U., Mellander, L., Nysom, K., Ringdén, O., Schrøder, H., Glomstein, A. and Gustafsson, G. (1996) Allogeneic bone marrow transplantation in first remission for children with very high risk acute lymphoblastic leukemia: A retrospective case-control study in the Nordic Countries.Bone Marrow Transplant 17, 357–63.

    PubMed  CAS  Google Scholar 

  59. Zhang, M-J., Hoelzer, D., Horowitz, M.M., Gale, R.P., Messerer, D., Klein, J.P., Löffler, H., Sobodnski, K.A., Thiel, E. and Weisdorf, DJ. for the Acute Lymphoblastic Leukemia Working Committee. (1995) Long-term follow-up of adults with acute lymphoblastic leukaemia in first remission treated with chemotherapy or bone marrow transplantation.Ann. Intern. Med. 123, 428–31.

    Google Scholar 

  60. Proctor, S.J., Hamilton, P.J., Reid, M.M., Carey, P., Hall, A., Leggat, H., Taylor, P., Hargreave, S., Kernahan, J., Pearson, A. and Evans, R.G.B. (1987) A comparative study of combination chemotherapy versus marrow transplant in first remission in ALL.Bone Marrow Transplant 2 (suppl 1), 21.

    Google Scholar 

  61. Sebban, C, Lepage, E., Vernant, J.P., Giuckman, E., Attal, M., Reiffers, J., Sutton, L., Racadot, E., Michallet, M., Maraninchi, D.et al. (1994) Allogeneic bone marrow transplantation in adult acute lymphoblastic leukaemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukaemia.J. Clin. Oncol. 12, 2580–7.

    PubMed  CAS  Google Scholar 

  62. Barrett, A.J., Horowitz, M.M., Pollock, B.H., Zhang, M-J., Bortin, M.M., Buchanan, G.R., Camitta, B.M., Ochs, J., Graham-Pole, J., Rowlings, P.A., Rimm, A.A., Klein, J.P., Shuster, J.J., Sobocinski, K.A. and Gale, R.P. (1994) Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission.N. Engl. J. Med. 331,1253–8.

    Article  PubMed  CAS  Google Scholar 

  63. Borgmann, A., Schmid, H., Hartmann, E., Baumgarten, E., Hermann, K., Klingebiel, T., Ebell, W., Zintl, F., Gadner, H. and Henze, G. 1996 for the Berlin-Frankfurt-Münster Study Group. (1995) Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis.Lancet 346, 873–6.

    Article  Google Scholar 

  64. Hermans, J., Suciu, S., Stijnen, Th., Aegerter, P., Gorin, N.C, Gratwohl, A., Hayat, M., Strickmans, P., Zittoun, R. and Zwaan, F.E. (1989) Treatment of acute myelogenous leukaemia: an EBMT-EORTC retrospective analysis of chemotherapy versus allogeneic or autologous bone marrow transplantation.Eur. J. Oncol. 25, 545–50.

    Article  CAS  Google Scholar 

  65. Zittoun, R., Mandelli, F., Willemze, R., De Witte, T., Labar, B., Resegotti, L., Leoni, F., Damasio, E., Visard, G., Papa, G., Caronia, F., Hayat, M., Stryckmanns, P., Rotoli, B., Leoni, P., Peetermans, M.E., Dardenne, M., Vegna, M.L., Petti, M.C., Solbu, G. and Suciu, S. 1962 for the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne Dell’Adulto (GIMENA) Leukemia Cooperative Groups. (1995) Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukaemia.N. Engl. J. Med. 332, 217–23.

    Article  Google Scholar 

  66. Gale, R.P., Horowitz, MM., Rees, J.K.H., Gray, R.G., Oken, M.M., Estey, E.H., Kim, K.M., Zhang, M.J., Ash, R.C., Atkinson, K., Champlin, R.E., Dicke, K.A., Gajewski, J.L., Helbig, W., Henslee-Downey, P.S., Hinterberger, W., Jacobsen, N., Keating, A., Klein, J.P., Marmont, A.M., Prentice, H.G., Reiffers, J., Rimms, A.A., Bortin, M.M.et al. (1996) Chemotherapy versus transplants for acute myelogenous leukemia in second remission.Leukemia 10, 13–9.

    PubMed  CAS  Google Scholar 

  67. Gratwohl, A. and Hermans, J. for the Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation (EBMT). (1996) Allogeneic bone marrow transplantation for chronic myeloid leukemia.Bone Marrow Transplant 17 (suppl 3), S7–S9.

    Google Scholar 

  68. Cliff, R.A. and Storb, R. (1996) Marrow transplantation for CML: the Seattle experience.Bone Marrow Transplant 17, (suppl 3), S1-S3.

    Google Scholar 

  69. Ringdén, O., Remberger, M., Mattsson, J., Aschan, J., Hägglund, H., Lönnqvist, B., Sparrelid, E. and Ljungman, P.Transplantation with unrelated bone marrow in leukaemic patients above 40 years of age (submitted).

  70. 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., Mitter-mueller, J., de Witte, T., Holler, E. and Ansari, H. 1985 for the European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. (1995) Graft-versus-leukemia effect of donor lymphocyte ransfusions in marrow grafted patients.Blood 86, 2041–50.

    Google Scholar 

  71. Grovas, A., Feig, S.A., O’Rourke, S., Valentino, L., Wiley, F., Hunt, L., Landaw, E.M. and Gajewski, J. (1994) Unrelated donor bone marrow transplantation in children.Cell Transplantation 3, 413–20.

    PubMed  CAS  Google Scholar 

  72. Björkstrand, B., Ljungmann, P., Svensson, H., Hermans, J., Alegre, A., Apperley, J., Bladé, J., Carlson, K., Cavo, M., Ferrant, A., Goldstone, A.H., de Laurenzi, A., Majolino, I., Marcus, R., Prentice, H.G., Remes, K., Samson, D., Sureda, A., Verdonck, L.F., Volin, L. and Gahrton, G. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma - a case-matched study from the European Group for Blood and Marrow Transplantation (EBMT) (in press).

  73. Ringdén, O., Mattson, J., Aschan, J., Barkholt, L., Dalianis, T., Hägglund, H., Ljungman, P., Lönnqvist, B., Winiarski, J. and Remberger, M. (1996) Experience with HLA-A, -B and -DR identical unrelated stem cell transplantations using immunosuppression with ATG, cyclosporin and methotrexate. In: Royal College of Physicians of Edinburgh. Consensus Conference of Unrelated Donor Bone Marrow Transplantation, p. 25.

  74. Storb, R., Prentice, R.L., Sullivan, K.M., Shulman, H.M., Deeg, H.J., Doney, K.C., Buckner, C.D., Clift, R., Witherspoon, R., Appelbaum, F., Sanders, J., Stewart, P. and Thomas, E.D. (1983) Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings: benefidal effect of a protective environment.N. Engl. J. Med. 308,302–7.

    PubMed  CAS  Google Scholar 

  75. Ringdén, O., Paulin, T., Lönnqvist, B. and Nilsson, B. (1985) An analysis of factors predisposing for chronic graft-versus-host disease.Exp. Hematol. 13, 1062–7.

    PubMed  Google Scholar 

  76. Lönnqvist, B., Aschan, J., Ljungman, P. and Ringdén, O. (1990) Long-term cyclosporin therapy may decrease the risk of chronic graft-versus-host disease.Br. J. Hematol. 74, 547–8.

    Article  Google Scholar 

  77. Weiden, P.L., Flournoy, N., Thomas, E.D., Prentice, R., Feifer, A., Buckner, CD. and Storb, R. (1979) Antileukemic effect of graft-versus-host disease in human recipients of allogeneic marrow grafts.N. Engl. J. Med. 300, 1068–73.

    PubMed  CAS  Google Scholar 

  78. Horowitz, M.M., Gale, R.P., Sondel, P.M., Goldman, J.M., Kersey, J., Kolb, H.-J., Rimm, A.A., Ringdén, O., Rozman, C, Speck, B., Truitt, R.L., Zwaan, F.E. and Bortin, M.M. (1989) Graft-versus-leukemia reactions following bone marrow transplantation in humans.Blood 75, 555–62.

    Google Scholar 

  79. Ringdén, 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. 1986 for the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. (1996) Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis.Bone Marrow Transplant. 18, 921–9.

    Google Scholar 

  80. Verdonck, L.F., Lokhorst, H.M., Dekker, A.W., Nieuwenhuis, H.K., Petersen, E.J. (1996) Graft-versus-myeloma effect in two cases.The Lancet 347, 800–1.

    Article  CAS  Google Scholar 

  81. Tricot, G., Vesole, D.H., Jagannath, S., Hilton, J., Munshi, N. and Barlogie, B. (1996) Graft-versus-myeloma effect: Proof of principle.Blood 87, 1196–8.

    PubMed  CAS  Google Scholar 

  82. Aschan, J., Lönnqvist, B., Ringdén, O., Kumlien, G. and Gahrton, G. (1996) Graft-versus-myeloma effect.Lancet 348, 346.

    Article  PubMed  CAS  Google Scholar 

  83. Ben-Yosef, R., Or, R., Nagler, A. and Slavin, S. (1996) Graft-versus-tumour and graft-versus-leukaemia effect in patient with concurrent breast cancer and acute myelocytic leukaemia.Lancet 348, 1242–3.

    Article  PubMed  CAS  Google Scholar 

  84. Kook, H., Goldman, F., Padley, D., Giller, R., Rumelhard, S., Holida, M., Lee, N., Peters, C, Comito, M., Huling, D. and Trigg, M. (1996) Reconstruction of the immune system after unrelated or partially matched T-cell depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.Blood 88, 1089–97.

    PubMed  CAS  Google Scholar 

  85. Paulin, T., Ringdén, O. and Lönnqvist, B. (1985) Faster immunological recovery after bone marrow transplantation in patients without cytomegalovirus infection.Transplantation 39, 377–84.

    Article  PubMed  CAS  Google Scholar 

  86. Paulin, T., Ringdén, O., Nilsson, B., Lönnqvist, B. and Gahrton, G. (1987) Variables predicting bacterial and fungal infections after allogeneic marrow engraftment.Transplantation 43, 393–8.

    Article  PubMed  CAS  Google Scholar 

  87. Paulin, T., Ringdén, O. and Nilsson, B. (1987) Immunological recovery after bone marrow transplantation: role of age, graft-versus-host disease, prednisolone treatment and infections.Bone Marrow Transplant 1, 317–28.

    PubMed  CAS  Google Scholar 

  88. Witherspoon, R.P., Storb, R., Ochs, H.D., Fluornoy, N., Kopecky, K.J., Sullivan, K.M., Deeg, J.H., Sosa, R., Noel, D.R., Atkinson, K. and Thomas, E.D. (1981) Recovery of antibody production in human allogeneic marrow graft recipients: Influence of time post transplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment.Blood 58, 360–8.

    PubMed  CAS  Google Scholar 

  89. Starzl, T.E., Abu-Elmagd, K., Tzakis, A., Fung, J.J., Porter, A. and Todo, S. (1991) Selected topics on FK506, with special reference to rescue of extrahepatic whole organ grafts, transplantation of ‘forbidden organs’, side-effects, mechanisms, and practical pharmacokinetics.Transplant. Proc. 23, 914–9.

    PubMed  CAS  Google Scholar 

  90. Fay, J.W., Wingard, J.R., Antin, J.H., Collins, R.H., Pineiro, L.A., Blazar, B.R., Saral, R., Bierer, B.E., Przepiorka, D., Fitzsimmons, W.E., Maher, R.M. and Weisdorf, D.J. (1996) FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogeneic bone marrow transplantation.Blood 87, 3514–9.

    PubMed  CAS  Google Scholar 

  91. Nash, R.A., Pineiro, L.A., Storb, R., Deeg, HJ., Fitzsimmons, W.E., Furlong, T., Hansen, J.A., Gooley, T., Maher, R.M., Martin, P., McSweeney, P.A., Sullivan, K.M., Anasetti, C. and Fay, J.W. (1996) FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors.Blood 88, 3634–41.

    PubMed  CAS  Google Scholar 

  92. Morris, R. (1992) Rapamycins: Antifungal, antirumor, antiproliferative and immunosuppressive macroides.Transplant Rev. 6, 39–87.

    Google Scholar 

  93. Kimball, P.M., Kernan, R.H. and Kahan, B. (1991) Production of synergistic by nonidentical mechanisms of immunosuppression by rapamycin and cyclosporin.Transplantation 51, 486–90.

    Article  PubMed  CAS  Google Scholar 

  94. Kawada, K. and Terasaki, P.I. (1987) Evidence for immunosuppression by high dose gammaglobulin.Exp. Haematol. 15, 133–6.

    CAS  Google Scholar 

  95. Klaesson, S., Ringdén, O., Markling, L., Remberger, M. and Lundquist, I. (1993) Immune modulatory effects of immunoglobulins on cell-mediated immune responsesin vitro.Scand. J. Immunol 38, 477–84.

    Article  PubMed  CAS  Google Scholar 

  96. Winston, DJ., Ho, W.G., Lin, C.-H., Bartony, K., Budinger, M., Gale, R. and Champlin, R. (1987) Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation.Ann. Intern. Med. 106, 12–8.

    PubMed  CAS  Google Scholar 

  97. Sullivan, K.M., Kopecky, K.J., Jocom, J., Fisher, L., Buckner, C.D., Meyers, J.D., Counts, G.W., Bowden, R.A., Petersen, F.B., Witherspoon, R.P., Budinger, M.D., Schwartz, R.S., Appelbaum, F.F., Ciift, R.A., Hansen, J.A., Sanders, J.E., Thomas, E.D. and Storb, R. (1990) Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation.N. Engl. J. Med. 323, 705–12.

    PubMed  CAS  Google Scholar 

  98. Piquet, P.F., Grau, G.E., Allet, B. and Vassali, P. (1987) Tumor necrosis factor/cachection is an effector of skin and gut lesions of the acute phase of graft-versus-host disease.J. Exp. Med. 166, 1280–9.

    Article  Google Scholar 

  99. Holler, E., Kolb, HJ., Möller, A., Kempeni, J., Liesenfeld, S., Pechumer, H., Lemacher, W., Ruckdeschel, G., Gleixner, B., Riedner, C, Ledderose, G., Brehm, G., Mittlemüller, J. and Wilmanns, W. (1990) Increased serum levels of tumor necrosis factor α precede major complications of bone marrow transplantation.Blood 75, 1011–6.

    PubMed  CAS  Google Scholar 

  100. Remberger, M. Ringdén, O. and Markling, L. (1995) TNFα levels are increased during bone marrow transplantation conditionings in patients who develop acute GVHD.Bone Marrow Transplant 15, 99–104.

    PubMed  CAS  Google Scholar 

  101. Holler, E., Kolb, H.J., Mirtermuller, J., Kaul, M., Ledderose, G., Duell, Th., Seeber, B., Schleuning, M., Hintermeier-Knabe, R., Ertl, E., Kempeni, J. and Wilmanns, W. (1995) Modulation of acute graft-versus-host disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNFα) release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNFα (MAK) 195F.Blood 86, 890–9.

    PubMed  CAS  Google Scholar 

  102. Sykes, M, Szot, G.L., Nguyen, P.L. and Pearson, D.A. (1995) Interleukin-12 inhibits murine graft-versus-host disease.Blood 86, 2429.

    PubMed  CAS  Google Scholar 

  103. Brunda, M.J., Luistro, L., Warner, R.R., Wright, R.B., Hubbard, B.R., Murphy, M., Wolf, S.F. and Gately, M.K. (1993) Antitumor and antimestatic activity of interleukin 12 against murine tumors.J. Exp. Med. 178, 1223.

    Article  PubMed  CAS  Google Scholar 

  104. Einsele, H., Steidle, M., Vallbracht, A., Saal, J.G., Ehringer, G. and Müller, C.A. (1991) Early occurence of HCMV infection after BMT as demonstrated by the PCR technique.Blood 77, 1104–10.

    PubMed  CAS  Google Scholar 

  105. Emanuel, D. (1990) Treatment of cytomegalovirus disease.Semin. Hematol 27, 22–7.

    PubMed  CAS  Google Scholar 

  106. Ringdén, O., Lönnqvist, B., Paulin, T., Ahlmén, J., Klintmalm, G., Wahren, B. and Lernestedt, J.O. (1986) Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients.J. Antimicrobial. Chemother.17, 373–87.

    Article  Google Scholar 

  107. Schmidt, G.M., Horak, D.A., Niland, J.C., Duncan, S.R., Forman, S.J., Zaia, J.A. and the City of Hope-Stanford-Syntex CMV Study Group. (1991) A randomized controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants.N. Engl. J. Med. 324, 1005–11.

    PubMed  CAS  Google Scholar 

  108. Ljungman, P., Loré, K., Aschan, J., Klaesson, S., Lewen-sohn-Fuchs, I., Lönnqvist, B., Ringdén, O., Winiarski, J. and Ehrnst, A. (1996) Use of a semi-quantitative PCR for cytomegalovirus DNA as a basis for pre-emptive antiviral therapy in allogeneic bone marrow transplant patients.Bone Marrow Transplant 17, 583–7.

    PubMed  CAS  Google Scholar 

  109. Tollemar, J., Ringdén, O., Boström, L., Nilsson, B. and Sundberg, B. (1989) Variables predicting deep fungal infections in bone marrow transplant recipients.Bone Marrow Transplant 4, 635–41.

    PubMed  CAS  Google Scholar 

  110. Shulman, H., Striker, G., Deeg, H.J., Kennedy, M., Storb, R. and Thomas, E.D. (1981) Nephrotoxicity of cyclosporin A after allogeneic marrow transplantation.N. Engl. J. Med. 305, 1392–5.

    PubMed  CAS  Google Scholar 

  111. Tollemar, J., Ringdén, O. and Tydén, G. (1990) Liposomal Amphotericin-B (AmBisome) treatment in solid organ and bone marrow transplant recipients. Efficacy and safety evaluation.Clin. Transplant 4, 167–75.

    Google Scholar 

  112. Ringdén, O., Meunier, F., Tollemar, J., Ricci, P., Tura, S., Kuse, E.R., Viviani, M., Gorin, N.C., Klastersky, J., Fenaux, P., Prentice, H.G. and Ksionski, G. (1991) Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients.J. Antimicrob. Chemother. 28 (suppl. B), 73–82.

    PubMed  Google Scholar 

  113. Ekelöf Andström, E., Ringdén, O., Remberger, M., Svahn, B.-M. and Tollemar, J. (1996) Safety and efficacy of liposomal amphotericin B in allogeneic bone marrow transplant recipients-improvements gained.Mycoses 39, 185–93.

    Article  Google Scholar 

  114. Tollemar, J. and Ringdén, O. (1995) Lipid formulations of Amphotericin B. Less toxicity but at what economic cost?Drug Safety 13, 207–18.

    PubMed  CAS  Google Scholar 

  115. Nemunaitis, J., Anasetti, C., Storb, R., Bianco, J.A., Buckner, C.D., Onetto, N., Martin, P., Sanders, J., Sullivan, K., Mori, M., Shannon-Dorcy, K., Bowden, R. and Appelbaum, F.R. (1992) Phase II trial of recombinant human granulocyte-macrophage colony-stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors.Blood 79, 2572–7.

    PubMed  CAS  Google Scholar 

  116. Klaesson, S., Ringdén, O., Ljungman, P., Lönnqvist, B. and Wennberg, L. (1994) Reduced blood transfusions requirements after allogeneic bone marrow transplantation, -results of a randomised, double-blind study with high dose erythropoietin.Bone Marrow Transplant 13, 397–402.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Clinical Immunology and Transplantation Surgery, Huddinge Hospital, S- 141 86, Huddinge, Sweden

    Olle Ringdén

Authors
  1. Olle Ringdén
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ringdén, O. Bone marrow transplantation using unrelated donors for haematological malignancies. Med Oncol 14, 11–22 (1997). https://doi.org/10.1007/BF02990940

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02990940

Keywords

Search

Navigation