Marrow Transplantation from Unrelated Volunteer Donors

  • Claudio Anasetti
  • Effie W. Petersdorf
  • Paul J. Martin
  • John A. Hansen
Part of the Cancer Treatment and Research book series (CTAR, volume 76)


Success of allogeneic marrow transplantation has initially been achieved by selecting human leukocyte antigen (HLA)-identical sibling donors. Subsequent clinical trials have evaluated the use of partially matched related donors and found that the degree of HLA incompatibility correlated with the risks of graft rejection and graft-versus-host disease (GVHD) [1,2].Transplants from related donors incompatible for only one HLA-A, -B, or -D/DRB1 antigen in recipients treated for hematological malignancy are associated with a probability of survival similar to that achieved in HLA-identical sibling transplants. In contrast, transplants from donors incompatible for two or three HLA antigens are associated with lower survival, despite using the best available immunosuppression for GVHD prophylaxis [3]. These clinical studies have formally demonstrated that HLA is the major histocompatibility complex in humans, and they have provided the scientific basis and rationale for HLA matching as the primary criteria for selecting unrelated donors for transplantation when patients lack an HLA matched family member. Less than 30% of the patients in North America have an HLA-matched sibling, and 3-5% have a one HLA-locus- mismatched relative. Therefore, for most patients in need of an allogeneic marrow transplant the only chance of finding a suitable donor is through the identification of an HLA-compatible unrelated volunteer. Initial case reports between 1973 and 1986 demonstrated that unrelated donor transplants could be curative in patients with leukemia or with other disorders of the lympho- hematopoietic system. Three major accomplishments have allowed unrelated donor transplants to become feasible and successful: (1) identification of HLA genes and their functional products [4]; (2) development of precise and efficient HLA typing methods using DNA technology [4]; and (3) the development of a network of registries containing more than 1.7 million HLA-typed donors worldwide [5]. To date more than 2500 patients with acute and chronic leukemias, lymphoma, myeloma, myelodysplasia, aplastic anemia, congenital errors of metabolism, and other diseases correctable by healthy allogeneic stem cells have been transplanted using marrow from unrelated volunteers [5]. Initial results have demonstrated a higher degree of GVHD in unrelated compared with related transplants despite matching for HLA-A, -B, -DRB1, -DQB, and -DPB, indicating that current assessment of histocompatibility is not yet complete [6].


Human Leukocyte Antigen Acute GVHD Human Leukocyte Antigen Class Chronic GVHD Unrelated Donor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beatty PG, Clift RA, Mickelson EM, Nisperos B, Flournoy N, Martin PJ, Sanders JE, Stewart P, Buckner CD, Storb R, Thomas ED, Hansen JA: Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 313:765–771, 1985.PubMedCrossRefGoogle Scholar
  2. 2.
    Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E, Nisperos B, O’Quigley J, Ramberg R, Sanders JE, Stewart P, Storb R, Sullivan KM, Witherspoon RP, Thomas ED, Hansen JA: Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med 320:197–204, 1989.PubMedCrossRefGoogle Scholar
  3. 3.
    Anasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, Thomas ED, Hansen JA: Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol 29:79–91, 1990.PubMedCrossRefGoogle Scholar
  4. 4.
    Dupont B, Yang SY: Histocompatibility. In. Forman SJ, Blume KG, Thomas ED (eds): Bone Marrow Transplantation. Boston: Blackwell Scientific, 1994, pp 22–40.Google Scholar
  5. 5.
    Anasetti C, Howe C, Petersdorf EW, Martin PJ, Hansen JA: Marrow Transplants from HLA matched unrelated donors: An NMDP update and the Seattle experience. Bone Marrow Transplant 13:693–695, 1994.PubMedGoogle Scholar
  6. 6.
    Hansen JA, Petersdorf EW, Yoon Choo S, Martin PJ, Anasetti C: Marrow transplants from HLA partially matched relatives and unrelated donors. Bone Marrow Transplant, 1995, in press.Google Scholar
  7. 7.
    Anasetti C, Hansen JA: Bone marrow transplantation from HLA-partially matched related donors and unrelated volunteer donors. In Forman SJ, Blume KG, Thomas ED (eds): Bone Marrow Transplantation. Boston: Blackwell Scientific, 1994, pp 665–679.Google Scholar
  8. 8.
    Yang SY: Nomenclature for HLA-A and HLA-B alleles detected by one-dimensional isoelectric focusing (ID-IEF) gel electrophoresis. In Dupont B (ed): Immunobiology of HLA, Volume I, Histocompatibility Testing 1987. New York: Springer-Verlag, 1989, pp 54–55.Google Scholar
  9. 9.
    Choo SY, Fan L, Hansen JA: A novel HLA-B27 allele maps B27 allospecificity to the region around position 70 in the α1 domain. J Immunol 147:174–180, 1991.PubMedGoogle Scholar
  10. 10.
    Fleischhauer K, Kernan NA, O’Reilly RJ, Dupont B, Yang SY: Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44. N Engl J Med 323:1818–1822, 1990.PubMedCrossRefGoogle Scholar
  11. 11.
    Mickelson E, Guthrie LA, Etzioni R, Anasetti C, Martin PJ, Hansen JA: Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: Matching for transplants from related haploidentical donors. Tissue Antigens 44:83–92, 1994.PubMedCrossRefGoogle Scholar
  12. 12.
    Petersdorf EW, Smith AG, Mickelson EM, Martin PJ, Hansen JA: Ten HLA-DR4 alleles defined by sequence polymorphisms within the DRB1 first domain. Immunogenetics 33: 267–275, 1991.PubMedCrossRefGoogle Scholar
  13. 13.
    Petersdorf EW, Smith AG, Haase AM, Martin PJ, Hansen JA: Polymorphism of HLA-DRw52-associated DRB1 genes as defined by sequence-specific oligonucleotide probe hybridization and sequencing. Tissue Antigens 38:169–177, 1991.PubMedCrossRefGoogle Scholar
  14. 14.
    Petersdorf EW, Smith AG, Mickelson EM, Longton GM, Anasetti C, Choo SY, Martin PJ, Hansen JA: The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease following unrelated donor marrow transplantation. Blood 81:1923–1932, 1993.PubMedGoogle Scholar
  15. 15.
    Deeg HJ, Anasetti C, Storb R, Doney K, Hansen JA: Cyclophosphamide plus ATG conditioning is insufficient for sustained hematopoietic reconstitution in patients with severe aplastic anemia transplanted with marrow from HLA-A, B, DRB matched unrelated donors [letter]. Blood 83:3417, 1994.PubMedGoogle Scholar
  16. 16.
    Anderson JE, Appelbaum FR, Storb R, Anasetti C: Busulfan (BU) and cyclophosphamide (CY) with or without total body irradiation (TBI) as preparative regimens for patientsundergoing allogeneic bone marrow transplantation (BMT) for myelodysplastic syndrome (MDS). Proceedings of the American Society of Hematology. Blood 82:377, 1993.Google Scholar
  17. 17.
    Slattery JT, Sanders JE, Buckner CD, Schaffer RL, Lambert KW, Langer FP, Anasetti C, Bensinger WI, Fisher LD, Appelbaum FR, Hansen JA: Graft rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant, 1995, in press.Google Scholar
  18. 18.
    Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, Gajewski J, Hansen JA, Henslee-Downey J, McCullough J, MeGlave P, Perkins HA, Phillips GL, Sanders J, Stroncek D, Thomas ED, Blume KG: Analysis of 462 transplants from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med 328:593–602, 1993.PubMedCrossRefGoogle Scholar
  19. 19.
    Sahebi F, Bolwell B, Cilley P, Frane M, Territo M, Gajewski J, Copelan E: Unrelated allogeneic bone marrow transplantation using high dose busulfan and cyclophosphamide (Bu-Cy) conditioning regimen. Proceedings at the American Society of Hematology. Blood 82:81, 1993.Google Scholar
  20. 20.
    Marmont AM, Horowitz MM, Gale RP, Sobocinski K, Ash RC, van Bekkum DW, Champlin RE, Dicke KA, Goldman JM, Good RA, Herzig RH, Hong R, Masaoka T, Rimm AA, Ringden O, Speck B, Weiner RS, Bortin MM: T-cell depletion of HLA-identical transplants in leukemia. Blood 79:2120–2130, 1991.Google Scholar
  21. 21.
    Ciccone E, Pende D, Viale O, Than A, Di Donato C, Orengo AM, Biassoni R, Verdiani S, Amoroso A, Moretta A, Moretta L: Involvement of HLA class I alleles in natural killer (NK) cell-specific functions: Expression of HLA-Cw3 confers selective protection from lysis by alloreactive NK clones displaying a defined specificity (specificity 2). J Exp Med 176:963–971, 1992.PubMedCrossRefGoogle Scholar
  22. 22.
    Colonna M, Brooks EG, Falco M, Ferrara GB, Strominger JL: Generation of allospecific natural killer cells by stimulation across a polymorphism of HLA-C. Science 260:1121–1124, 1993.PubMedCrossRefGoogle Scholar
  23. 23.
    Petersdorf EW, Stanley JF, Martin PJ, Hansen JA: Molecular diversity of the HLA-C locus in unrelated marrow transplantation. Tissue Antigens 44:93–99, 1994.PubMedCrossRefGoogle Scholar
  24. 24.
    Anasetti C, Anderson G, Appelbaum FR, Buckner CD, Martin PJ, Nemunaitis J, Singer J, Storb R, Sullivan KM, Thomas ED, Hansen JA: Phase III study of rhGM-CSF in allogeneic marrow transplantation from unrelated donors. Proceedings at the American Society of Hematology. Blood 82:454, 1993.Google Scholar
  25. 25.
    Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen JA, Hill R, Lum L, Martin P, McGuffin R, Sanders J, Stewart P, Sullivan K, Witherspoon R, Yee G, Thomas ED: Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 314:729–735, 1986.PubMedCrossRefGoogle Scholar
  26. 26.
    Beatty PG, Hansen JA, Thomas ED, Sanders JE, Martin PJ, Bearman SI, Longton GM, Anasetti C, Petersdorf EW, Mickelson EM, Pepe MS, Appelbaum FR, Buckner CD, Clift RA, Petersen FB, Stewart PS, Storb RF, Sullivan KM, Tesler MC, Witherspoon RP: Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies. Transplantation 2:443–446, 1991.CrossRefGoogle Scholar
  27. 27.
    Beatty PG, Anasetti C, Hansen JA, Longton GM, Sanders JE, Martin PJ, Mickelson ME, Choo SY, Petersdorf EW, Pepe MS, Appelbaum FR, Bearman SI, Buckner CD, Clift RA, Petersen FB, Singer J, Stewart PS, Storb RS, Sullivan KM, Tesler MC, Witherspoon RP, Thomas ED: Marrow transplantation from unrelated donors for treatment of hematologic malignancies: Effect of mismatching for one HLA locus. Blood 81:249–253, 1993.PubMedGoogle Scholar
  28. 28.
    Anasetti C, Martin PJ, Mickelson EM, Petersdorf EW, Hansen JA: Effect of HLA mismatching in marrow transplantation from unrelated donors. Proceedings at the TSANZ First International Symposium on Cytokines in Bone Marrow Transplantation held at Christchurch, New Zealand, 1993.Google Scholar
  29. 29.
    Nash RA, Pepe MS, Storb R, Longton G, Pettinger M, Anasetti C, Appelbaum FR, Bowden R, Deeg HJ, Doney K, Martin PJ, Sullivan KM, Sanders J, Witherspoon PR: Acute graft-versus-host disease: Analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 80:1838–1845, 1992.PubMedGoogle Scholar
  30. 30.
    Nemunaitis J, Anasetti C, Bianco J, Hansen JA, Singer JW: rhGM-CSF after allogeneic bone marrow transplantation from unrelated donors: A pilot study of cyclosporine and prednisone as graft-versus-host disease prophylaxis. Leuk Lymphoma 10:177–181, 1993.PubMedCrossRefGoogle Scholar
  31. 31.
    Chao NJ, Schmidt GM, Niland JC, Amylon MD, Dagis AC, Long GD, Mademanee AP, Negrin RS, O’Donnell MR, Parker PM, Smith EP, Snyder DS, Stein AS, Wong RM, Blume KG, Forman SJ: Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med 329:1225–1230, 1993.PubMedCrossRefGoogle Scholar
  32. 32.
    Leelasiri A, Greer JP, Stein RS, Goodman S, Edwards JR, Wolff SN: GVHD prophylaxis for matched unrelated donor bone marrow transplantation (MUD): Comparison between cyclosporine-methotrexate-methylprednisolone (CSA-MTX-MP) and CSA-MTX. Proceedings at the American Society of Hematology. Blood 82:420, 1993.Google Scholar
  33. 33.
    Nademanee A, Schmidt GM, Littrell B, Niland JC, Parker PM, O’Donnell MR, Snyder DS, Stein A, Smith E, Molina A, Wong KK, Margolin K, Forman SJ: The outcome of matched unrelated donor (MUD) bone marrow transplantation in patients with hematologic malignancies utilizing molecular typing for donor selection. Proceedings at the American Society of Hematology. Blood 82:79, 1993.Google Scholar
  34. 34.
    Fay JW, Collins RH, Pineiro LA, Nemunaitis J, Aro R, Fitzsimmons W: FK506 to prevent graft-versus-host disease (GVHD) after allogeneic marrow transplantation (AMT) using unrelated marrow donors (UMD)-A phase II study. Proceedings at the American Society of Hematology. Blood 82:420, 1993.Google Scholar
  35. 35.
    Ash RC, Horowitz MM, Gale RP, van Bekkum DW, Casper JT, Gordon-Smith EC, Henslee PJ, Kolb HJ, Lowenberg B, Masaoka T, McGlave PB, Rimm AA, Ringden O, van Rood JJ, Sondel PM, Vowels MR, Bortin MM: Bone marrow transplantation from related donors other than HLA-identical siblings: Effect of T cell depletion. Bone Marrow Transplant 7:443–452, 1991.PubMedGoogle Scholar
  36. 36.
    Ash RC, Casper JT, Chitambar CR, Hansen R, Bunin N, Truitt RL, Lawton C, Murray K, Hunter J, Baxter-Lowe LA, Gottschall JL, Oldham K, Anderson T, Camitta B, Menitove J: Successful allogeneic transplantation of T-cell-depleted bone marrow from closely HLA-matched unrelated donors. N Engl J Med 322:485–494, 1990.PubMedCrossRefGoogle Scholar
  37. 37.
    Drobyski WR, Ash RC, Casper JT, McAuliffe T, Horowitz MM, Lawton C, Keever C, Baxter-Lowe LA, Camitta B, Garbrecht F, Pietryga D, Hansen R: Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia. Blood 83:1980–1987, 1994.PubMedGoogle Scholar
  38. 38.
    Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G, Meyers J: Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intein Med 118:173–178, 1993.Google Scholar
  39. 39.
    Goodrich JM, Mori M, Gleaves CA, Du Mond C, Cays M, Ebeling DF, Buhles WC, DeArmond B, Meyers JD: Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med 325:1601–1607, 1991.PubMedCrossRefGoogle Scholar
  40. 40.
    Clift RA, Buckner CD, Thomas ED, Bensinger WI, Bowden R, Bryant E, Deeg HJ, Doney KC, Fisher LD, Hansen JA, Martin P, McDonald GB, Sanders JE, Schach G, Singer J, Storb R, Sullivan KM, Witherspoon RP, Appelbaum FR: Marrow transplantation for chronic myeloid leukemia. Blood 84:2036–2043, 1994.PubMedGoogle Scholar
  41. 41.
    Busca A, Anasetti C, Anderson G, Appelbaum FR, Buckner CD, Doney K, Martin PJ, Petersdorf E, Sanders JE, Hansen JA: Unrelated donor or autologous marrow transplantation for treatment of acute leukemia. Blood 83:3077–3084, 1994.PubMedGoogle Scholar
  42. 42.
    Kernan NA, Kahn R, Landrey C, O’Reilly RJ, Dupont B, Yang SY: HLA-matching for unrelated bone marrow transplantation: Selection of donors based on class IIEF variants. Proceedings at the International Society of Experimental Hematology. 18:508, 1990.Google Scholar
  43. 43.
    McGlave P, Bartsch G, Anasetti C, Ash R, Beatty P, Gajewski J, Kernan NA: Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: Initial experience of the National Marrow Donor Program. Blood 81:543–550, 1993.PubMedGoogle Scholar
  44. 44.
    Hows JM, Szydlo R, Anasetti C, Camitta B, Gajewsky J, Gluckman E: Unrelated donor marrow transplants for severe acquired aplastic anemia. Bone Marrow Transplant 10:102–106, 1992.PubMedGoogle Scholar
  45. 45.
    Filipovich AH, Shapiro RS, Ramsay NK, Kim T, Blazar B, Kersey J, McGlave P: Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies. Blood 80:270–276, 1992.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Claudio Anasetti
  • Effie W. Petersdorf
  • Paul J. Martin
  • John A. Hansen

There are no affiliations available

Personalised recommendations