Hematopoietic Stem Cell Transplantation: Reflections on Yesterday and Thoughts for Tomorrow

  • Andrew D. LeavittEmail author
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Biomedical science is entering a new era with exciting prospects for using cellular therapy to treat a wide spectrum of human diseases from nerve injury to diabetes, myocardial infarction, and more. Hematopoietic stem cell (HSC) transplantation has been used to treat patients for nearly half a century. The experiences and lessons learned over those 50 years are both informative and encouraging. This chapter distills the history of HSC transplantation to provide an orientation to the past that can be used to more wisely navigate the future of cell therapy. The details presented help the reader appreciate that developing novel cell therapy can be a struggle and that chance will likely continue to play a role in future success. However, it also becomes apparent that attention to fundamental details, such as choice of cell type or types, where to obtain the cells, how to handle and process the cells, how to prepare and select patients, how to evaluate success and failure, and how to organize the biomedical community to serve the good of patients, are all critical for new cell therapy to become a reality.


Hematopoietic Stem Cell Hematopoietic Stem Cell Transplantation Aplastic Anemia Total Body Irradiation Stem Cell Therapy 
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.



Bone marrow transplantation


Graft-versus-host disease




Human lymphocyte antigen


Hematopoietic stem cells


Peripheral blood stem cells


Umbilical cord blood


  1. 1.
    Orkin SH, Zon LI (2008) Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132(4):631–644PubMedCrossRefGoogle Scholar
  2. 2.
    Pasquini MC, Wang Z (2010) Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides. Accessed 9 Jul 2011
  3. 3.
    Perry AR, Linch DC (1996) The history of bone-marrow transplantation. Blood Rev 10(4):215–219PubMedCrossRefGoogle Scholar
  4. 4.
    Thomas ED (2005) Bone marrow transplantation from the personal viewpoint. Int J Hematol 81(2):89–93PubMedCrossRefGoogle Scholar
  5. 5.
    Shouse SS, Warren SL, Whipple GH (1931) II. Aplasia of marrow and fatal intoxication in dogs produced by roentgen radiation of all bones. J Exp Med 53(3):421–435PubMedCrossRefGoogle Scholar
  6. 6.
    Rekers PE, Coulter MP, Warren SL (1950) Effect of transplantation of bone marrow into irradiated animals. Arch Surg 60(4):635–667Google Scholar
  7. 7.
    Jacobson LO, Marks EK, Robson MJ, Gaston E, Zirkle RE (1949) The effect of spleen protetction on mortality following x-irradiation. J Lab Clin Med 34:1538–1543Google Scholar
  8. 8.
    Lorenz E, Uphoff D, Reid TR, Shelton E (1951) Modification of irradiation injury in mice and guinea pigs by bone marrow injections. J Natl Cancer Inst 12(1):197–201PubMedGoogle Scholar
  9. 9.
    Main JM, Prehn RT (1955) Successful skin homografts after the administration of high dosage X radiation and homologous bone marrow. J Natl Cancer Inst 15(4):1023–1029PubMedGoogle Scholar
  10. 10.
    Ford CE, Hamerton JL, Barnes DW, Loutit JF (1956) Cytological identification of radiation-chimaeras. Nature 177(4506):452–454PubMedCrossRefGoogle Scholar
  11. 11.
    Barnes DW, Corp MJ, Loutit JF, Neal FE (1956) Treatment of murine leukaemia with X rays and homologous bone marrow: preliminary communication. Br Med J 2(4993):626–627PubMedCrossRefGoogle Scholar
  12. 12.
    Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW (1957) Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 257(11):491–496PubMedCrossRefGoogle Scholar
  13. 13.
    Congdon CC, Uphoff D, Lorenz E (1952) Modification of acute irradiation injury in mice and guinea pigs by injection of bone marrow: a histopathologic study. J Natl Cancer Inst 13(1):73–107PubMedGoogle Scholar
  14. 14.
    Thomas ED, Lochte HL Jr, Cannon JH, Sahler OD, Ferrebee JW (1959) Supralethal whole body irradiation and isologous marrow transplantation in man. J Clin Invest 38:1709–1716PubMedCrossRefGoogle Scholar
  15. 15.
    Bortin MM (1970) A compendium of reported human bone marrow transplants. Transplantation 9(6):571–587PubMedCrossRefGoogle Scholar
  16. 16.
    Billingham RE, Brent L, Medawar PB (1953) Actively acquired tolerance of foreign cells. Nature 172(4379):603–606PubMedCrossRefGoogle Scholar
  17. 17.
    Nisbet NW, Heslop BF (1962) Runt disease-II. Br Med J 1(5273):206–213PubMedCrossRefGoogle Scholar
  18. 18.
    Nisbet NW, Heslop BF (1962) Runt disease. Br Med J 1(5272):129–135,contdPubMedCrossRefGoogle Scholar
  19. 19.
    Billingham RE (1966) The biology of graft-versus-host reactions. Harvey Lect 62:21–78PubMedGoogle Scholar
  20. 20.
    Billingham RE, Silvers WK (1959) The induction of tolerance of skin homografts in rats with pooled cells from multiple donors. J Immunol 83:667–679PubMedGoogle Scholar
  21. 21.
    Cavins JA, Kasakura S, Thomas ED, Ferrebee JW (1962) Recovery of lethally irradiated dogs following infusion of autologous marrow stored at low temperature in dimethylsulphoxide. Blood 20:730–734PubMedGoogle Scholar
  22. 22.
    Thomas ED, Collins JA, Herman EC Jr, Ferrebee JW (1962) Marrow transplants in lethally irradiated dogs given methotrexate. Blood 19:217–228PubMedGoogle Scholar
  23. 23.
    Epstein RB, Storb R, Ragde H, Thomas ED (1968) Cytotoxic typing antisera for marrow grafting in littermate dogs. Transplantation 6(1):45–58PubMedCrossRefGoogle Scholar
  24. 24.
    Storb R, Epstein RB, Bryant J, Ragde H, Thomas ED (1968) Marrow grafts by combined marrow and leukocyte infusions in unrelated dogs selected by histocompatibility typing. Transplantation 6(4):587–593PubMedCrossRefGoogle Scholar
  25. 25.
    Storb R, Rudolph RH, Thomas ED (1971) Marrow grafts between canine siblings matched by serotyping and mixed leukocyte culture. J Clin Invest 50(6):1272–1275PubMedCrossRefGoogle Scholar
  26. 26.
    Thomas E et al (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292(16):832–843PubMedCrossRefGoogle Scholar
  27. 27.
    Thomas ED et al (1975) Bone-marrow transplantation (second of two parts). N Engl J Med 292(17):895–902PubMedCrossRefGoogle Scholar
  28. 28.
    Thomas ED et al (1977) One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 49(4):511–533PubMedGoogle Scholar
  29. 29.
    Blume KG, Beutler E (1979) Allogeneic bone marrow transplantation for acute leukemia. JAMA 241(16):1686PubMedCrossRefGoogle Scholar
  30. 30.
    Thomas ED et al (1979) Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med 301(11):597–599PubMedCrossRefGoogle Scholar
  31. 31.
    Gale RP et al (1994) Identical-twin bone marrow transplants for leukemia. Ann Intern Med 120(8):646–652PubMedGoogle Scholar
  32. 32.
    Johnson FL, Look AT, Gockerman J, Ruggiero MR, Dalla-Pozza L, Billings FT III (1984) Bone-marrow transplantation in a patient with sickle-cell anemia. N Engl J Med 311(12):780–783PubMedCrossRefGoogle Scholar
  33. 33.
    Thomas ED et al (1982) Marrow transplantation for thalassaemia. Lancet 2(8292):227–229PubMedGoogle Scholar
  34. 34.
    Hsieh MM et al (2009) Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med 361(24):2309–2317PubMedCrossRefGoogle Scholar
  35. 35.
    Korbling M et al (1995) Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. Blood 85(6):1659–1665PubMedGoogle Scholar
  36. 36.
    Socinski MA, Cannistra SA, Elias A, Antman KH, Schnipper L, Griffin JD (1988) Granulocyte-macrophage colony stimulating factor expands the circulating haemopoietic progenitor cell compartment in man. Lancet 1(8596):1194–1198PubMedCrossRefGoogle Scholar
  37. 37.
    Korbling M et al (1995) Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy-1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease. Blood 86(7):2842–2848PubMedGoogle Scholar
  38. 38.
    Schmitz N et al (1995) Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor). Blood 85(6):1666–1672PubMedGoogle Scholar
  39. 39.
    Azevedo WM et al (1995) Allogeneic transplantation with blood stem cells mobilized by rhG-CSF for hematological malignancies. Bone Marrow Transplant 16(5):647–653PubMedGoogle Scholar
  40. 40.
    Russell JA et al (1995) Collection of progenitor cells for allogeneic transplantation from peripheral blood of normal donors. Bone Marrow Transplant 15(1):111–115PubMedCrossRefGoogle Scholar
  41. 41.
    Bensinger WI et al (1995) Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 85(6):1655–1658PubMedGoogle Scholar
  42. 42.
    Dreger P, Suttorp M, Haferlach T, Loffler H, Schmitz N, Schroyens W (1993) Allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for tretment of engrftment failure after bone marrow transplantaion. Blood 81:1404–1407PubMedGoogle Scholar
  43. 43.
    Bensinger WI et al (1993) The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis. Blood 81(7):1883–1888PubMedGoogle Scholar
  44. 44.
    Caspar CB, Seger RA, Burger J, Gmur J (1993) Effective stimulation of donors for granulocyte transfusions with recombinant methionyl granulocyte colony-stimulating factor. Blood 81(11):2866–2871PubMedGoogle Scholar
  45. 45.
    Hansen JA, Clift RA, Thomas ED, Buckner CD, Storb R, Giblett ER (1980) Transplantation of marrow from an unrelated donor to a patient with acute leukemia. N Engl J Med 303(10):565–567PubMedCrossRefGoogle Scholar
  46. 46.
    Broxmeyer HE et al (1989) Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci USA 86(10):3828–3832PubMedCrossRefGoogle Scholar
  47. 47.
    Gluckman E et al (1989) Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med 321(17):1174–1178PubMedCrossRefGoogle Scholar
  48. 48.
    Wagner JE, Gluckman E (2010) Umbilical cord blood transplantation: the first 20 years. Semin Hematol 47(1):3–12PubMedCrossRefGoogle Scholar
  49. 49.
    Brunstein CG, Laughlin MJ (2010) Extending cord blood transplant to adults: dealing with problems and results overall. Semin Hematol 47(1):86–96PubMedCrossRefGoogle Scholar
  50. 50.
    Anonymous (2005) Cord blood: establishing a national hematopoietic stem cell bank program, a 2005 report from The Institue of Medicine of The National Academy of Sciences. Accessed 9 Jul 2011
  51. 51.
    Linker CA (2003) Autologous stem cell transplantation for acute myeloid leukemia. Bone Marrow Transplant 31(9):731–738PubMedCrossRefGoogle Scholar
  52. 52.
    Linker CA, Damon LE, Ries CA, Navarro WA, Case D, Wolf JL (2002) Autologous stem cell transplantation for advanced acute myeloid leukemia. Bone Marrow Transplant 29(4):297–301PubMedCrossRefGoogle Scholar
  53. 53.
    Linker CA, Ries CA, Damon LE, Rugo HS, Wolf JL (1993) Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen. Blood 81(2):311–318PubMedGoogle Scholar
  54. 54.
    Brenner MK et al (1993) Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients. Lancet 342(8880):1134–1137PubMedCrossRefGoogle Scholar
  55. 55.
    Brenner MK et al (1993) Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet 341(8837):85–86PubMedCrossRefGoogle Scholar
  56. 56.
    Deisseroth AB et al (1994) 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 83(10):3068–3076PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Departments of Laboratory Medicine and Medicine, UCSF Adult Blood and Marrow Transplant LaboratoryUniversity of CaliforniaSan FranciscoUSA

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