After fifty years of investigations into the use of pluripotent haematopoietic stem-cell transplantation for cancer therapy, this procedure has progressed from one that was thought to be plagued with insurmountable complications to a standard treatment for many haematological malignancies. How have these hurdles been overcome, and how can the therapy be expanded to include patients who are too old or medically infirm to tolerate conventional transplant approaches?
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Jacobson, L. O., Marks, E. K., Robson, M. J., Gaston, E. O. & Zirkle, R. E. Effect of spleen protection on mortality following X-irradiation. J. Lab. Clin. Med. 34, 1538–1543 (1949).
Lorenz, E., Uphoff, D., Reid, T. R. & Shelton, E. Modification of irradiation injury in mice and guinea pigs by bone marrow injections. J. Natl Cancer Inst. 12, 197–201 (1951).
van Bekkum, D. W. & de Vries, M. J. Radiation Chimaeras (ed. Rijswijk, Z. H.) (Logos Press Limited, London, 1967).
Barnes, D. W. H. & Loutit, J. F. What is the recovery factor in spleen? Nucleonics 12, 68–71 (1954).
Main, J. M. & Prehn, R. T. Successful skin homografts after the administration of high dosage X radiation and homologous bone marrow. J. Natl Cancer Inst. 15, 1023–1029 (1955).
Trentin, J. J. Mortality and skin transplantability in X-irradiated mice receiving isologous or heterologous bone marrow. Proc. Soc. Exp. Biol. Med. 92, 688–693 (1956).
Ford, C. E., Hamerton, J. L., Barnes, D. W. H. & Loutit, J. F. Cytological identification of radiation-chimaeras. Nature 177, 452–454 (1956).
Nowell, P. C., Cole, L. J., Habermeyer, J. G. & Roan, P. L. Growth and continued function of rat marrow cells in X-radiated mice. Cancer Res. 16, 258–261 (1956).
Woodruff, M. F. A. . The Transplantation of Tissues and Organs (Charles C. Thomas, Springfield, Illinois, 1960).
Brent, L. A History of Transplantation Immunology (Academic, San Diego, 1997).
Thomas, E. D. & Storb, R. in Hematopoietic Cell Transplantation 2nd edn (eds Thomas, E. D., Blume, K. G. & Forman, S. J.) 1–11 (Blackwell Science, Boston, 1999).
Thomas, E. D. & Blume, K. G. Historical markers in the development of allogeneic hematopoietic cell transplantation. Biol. Blood Marrow Transplant. 5, 341–346 (1999).
Thomas, E. D., Lochte, H. L. Jr, Lu, W. C. & Ferrebee, J. W. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med. 257, 491–496 (1957).
Thomas, E. D., Lochte, H. L. Jr, Cannon, J. H., Sahler, O. D. & Ferrebee, J. W. Supralethal whole body irradiation and isologous marrow transplantation in man. J. Clin. Invest. 38, 1709–1716 (1959).
Barnes, D. W. H., Corp, M. J., Loutit, J. F. & Neal, F. E. Treatment of murine leukaemia with X-rays and homologous bone marrow. BMJ 2, 626–627 (1956).
Mathé, G., Amiel, J. L., Schwarzenberg, L., Catton, A. & Schneider, M. Adoptive immunotherapy of acute leukemia: experimental and clinical results. Cancer Res. 25, 1525–1531 (1965).
Andrews, G. A. Criticality accidents in Vinca, Yugoslavia, and Oak Ridge Tennessee. Am. J. Roentgenol. Radium Ther. Nucl. Med. 93, 56–74 (1965).
McGovern, J. J. Jr, Russel, P. S., Atkins, L. & Webster, E. W. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N. Engl. J. Med. 260, 675–683 (1959).
Beilby, J. O., Cade, I. S., Jeliffe, A. M., Parkin, D. M. & Stewart, J. W. Prolonged survival of a bone-marrow graft resulting in a blood group chimera. BMJ 1, 96–99 (1960).
Thomas, E. D. et al. Bone-marrow transplantation. N. Engl. J. Med. 292, 832–843, 895–902 (1975).
Santos, G. W. Busulfan (Bu) and cyclophosphamide (Cy) for marrow transplantation. Bone Marrow Transplant. 4, 236–239 (1989).
Mannick, J. A., Lochte, H. L. Jr, Ashley, C. A., Thomas, E. D. & Ferrebee, J. W. Autografts of bone marrow in dogs after lethal total-body radiation. Blood 15, 255–266 (1960).
Cavins, J. A., Kasakura, S., Thomas, E. D. & Ferrebee, J. W. Recovery of lethally irradiated dogs following infusion of autologous marrow stored at low temperature in dimethyl-sulphoxide. Blood 20, 730–734 (1962).
Thomas, E. D., LeBlond, R., Graham, T. & Storb, R. Marrow infusions in dogs given midlethal or lethal irradiation. Radiat. Res. 41, 113–124 (1970).
Storb, R., Rudolph, R. H. & Thomas, E. D. Marrow grafts between canine siblings matched by serotyping and mixed leukocyte culture. J. Clin. Invest. 50, 1272–1275 (1971).
Storb, R. et al. What radiation dose for DLA-identical canine marrow grafts? Blood 72, 1300–1304 (1988).
Storb, R. & Deeg, H. J. Failure of allogeneic canine marrow grafts after total body irradiation: allogeneic 'resistance' vs transfusion induced sensitization. Transplantation 42, 571–580 (1986).
Bodenberger, U. et al. Fractionated total body irradiation and autologous bone marrow transplantation in dogs: hemopoietic recovery after various marrow cell doses. Exp. Hematol. 8, 384–394 (1980).
Deeg, H. J. et al. Single dose or fractionated total body irradiation and autologous marrow transplantation in dogs: effects of exposure rate, fraction size and fractionation interval on acute and delayed toxicity. Int. J. Radiat. Oncol. Biol. Phys. 15, 647–653 (1988).
Storb, R. et al. Comparison of fractionated to single-dose total body irradiation in conditioning canine littermates for DLA-identical marrow grafts. Blood 74, 1139–1143 (1989).
Cavins, J. A., Scheer, S. C., Thomas, E. D. & Ferrebee, J. W. The recovery of lethally irradiated dogs given infusions of autologous leukocytes preserved at 80°C. Blood 23, 38–43 (1964).
Storb, R., Epstein, R. B., Ragde, H. & Thomas, E. D. Marrow engraftment by allogeneic leukocytes in lethally irradiated dogs. Blood 30, 805–811 (1967).
Körbling, M. et al. Albumin density gradient purification of canine hemopoietic blood stem cells (HBSC): long-term allogeneic engraftment without GVH-reaction. Exp. Hematol. 7, 277–288 (1979).
Snell, G. D. The Nobel Lectures in Immunology. Lecture for the Nobel Prize for Physiology or Medicine, 1980: studies in histocompatibility. Scand. J. Immunol. 36, 513–526 (1992).
Epstein, R. B., Storb, R., Ragde, H. & Thomas, E. D. Cytotoxic typing antisera for marrow grafting in littermate dogs. Transplantation 6, 45–58 (1968).
Deeg, H. J. et al. Joint Report of the Third International Workshop on Canine Immunogenetics. I. Analysis of homozygous typing cells. Transplantation 41, 111–117 (1986).
Bull, R. W. et al. Joint Report of the Third International Workshop on Canine Immunogenetics. II. Analysis of the serological typing of cells. Transplantation 43, 154–161 (1987).
Wagner, J. L., Burnett, R. C., Works, J. D. & Storb, R. Molecular analysis of DLA-DRBB1 polymorphism. Tissue Antigens 48, 554–561 (1996).
Burnett, R. C., DeRose, S. A., Wagner, J. L. & Storb, R. Molecular analysis of six dog leukocyte antigen class I sequences including three complete genes, two truncated genes, and one full-length processed gene. Tissue Antigens 49, 484–495 (1997).
Storb, R., Epstein, R. B., Graham, T. C. & Thomas, E. D. Methotrexate regimens for control of graft-versus-host disease in dogs with allogeneic marrow grafts. Transplantation 9, 240–246 (1970).
Storb, R. & Thomas, E. D. Graft-versus-host disease in dog and man: the Seattle experience. Immunol. Rev. 88, 215–238 (1985).
Uphoff, D. E. Alteration of homograft reaction by A-methopterin in lethally irradiated mice treated with homologous marrow. Proc. Soc. Exp. Biol. Med. 99, 651–653 (1958).
Thomas, E. D., Collins, J. A., Herman, E. C. Jr & Ferrebee, J. W. Marrow transplants in lethally irradiated dogs given methotrexate. Blood 19, 217–228 (1962).
Lochte, H. L. Jr, Levy, A. S., Guenther, D. M., Thomas, E. D. & Ferrebee, J. W. Prevention of delayed foreign marrow reaction in lethally irradiated mice by early administration of methotrexate. Nature 196, 1110–1111 (1962).
Deeg, H. J. et al. Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of tolerance. Transplantation 34, 30–35 (1982).
Deeg, H. J. et al. Combined immunosuppression with cyclosporine and methotrexate in dogs given bone marrow grafts from DLA-haploidentical littermates. Transplantation 37, 62–65 (1984).
Storb, R. et al. FK506 and methotrexate prevent graft-versus-host disease in dogs given 9.2 Gy total body irradiation and marrow grafts from unrelated DLA-nonidentical donors. Transplantation 56, 800–807 (1993).
Tsoi, M.-S. et al. Canine marrow transplantation: are serum blocking factors necessary to maintain the stable chimeric state? J. Immunol. 114, 531–539 (1975).
Atkinson, K. et al. In vitro tests correlating with presence or absence of graft-vs-host disease in DLA nonidentical canine radiation chimeras: evidence that clonal abortion maintains stable graft-host tolerance. J. Immunol. 124, 1808–1814 (1980).
Deeg, H. J., Atkinson, K., Weiden, P. L. & Storb, R. Mechanisms of tolerance in canine radiation chimeras. Transplant. Proc. 19 (Suppl. 7), 75–81 (1987).
Weiden, P. L. et al. Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance. J. Immunol. 116, 1212–1219 (1976).
Epstein, R. B., Storb, R., Clift, R. A. & Thomas, E. D. Autologous bone marrow grafts in dogs treated with lethal doses of cyclophosphamide. Cancer Res. 29, 1072–1075 (1969).
Storb, R., Epstein, R. B., Rudolph, R. H. & Thomas, E. D. Allogeneic canine bone marrow transplantation following cyclophosphamide. Transplantation 7, 378–386 (1969).
Santos, G. W. & Owens, A. H. Jr. Allogeneic marrow transplants in cyclophosphamide treated mice. Transplant. Proc. 1, 44–46 (1969).
Thomas, E. D. et al. Allogeneic marrow grafting for hematologic malignancy using HL-A matched donor–recipient sibling pairs. Blood 38, 267–287 (1971).
Santos, G. W. et al. Marrow transplantation in man following cyclophosphamide. Transplant. Proc. 3, 400–404 (1971).
Storb, R., Buckner, C. D., Dillingham, L. A. & Thomas, E. D. Cyclophosphamide regimens in rhesus monkeys with and without marrow infusion. Cancer Res. 30, 2195–2203 (1970).
Storb, R., Epstein, R. B., Bryant, J., Ragde, H. & Thomas, E. D. Marrow grafts by combined marrow and leukocyte infusions in unrelated dogs selected by histocompatibility typing. Transplantation 6, 587–593 (1968).
Storb, R. et al. Marrow grafts between DL-A-matched canine littermates. Transplantation 15, 92–100 (1973).
Storb, R., Prentice, R. L. & Thomas, E. D. Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival. J. Clin. Invest. 59, 625–632 (1977).
Storb, R. et al. 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).
Ratanatharathorn, V. et al. Phase III study comparing methotrexate and tacrolimus (Prograf, FK506) with methotrexate and cyclosporine for graft-versus-host-disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 92, 2303–2314 (1998).
Martin, P. J. et al. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 66, 664–672 (1985).
Marmont, A. M. et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 78, 2120–2130 (1991).
Goldman, J. M. et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion. Ann. Intern. Med. 108, 806–814 (1988).
Aversa, F. et al. Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia. J. Clin. Oncol. 17, 1545–1550 (1999).
Papadopoulos, E. B. et al. T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood 91, 1083–1090 (1998).
Mackinnon, S. et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 86, 1261–1268 (1995).
Thomas, E. D. et al. Cure of leukemia by marrow transplantation. Leuk. Res. 1, 67–70 (1977).
Thomas, E. D. et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 49, 511–533 (1977).
Weiden, P. L. et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N. Engl. J. Med. 300, 1068–1073 (1979).
Sullivan, K. M. et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 73, 1720–1728 (1989).
Weiden, P. L. et al. Antileukemic effect of chronic graft-versus-host disease. Contribution to improved survival after allogeneic marrow transplantation. N. Engl. J. Med. 304, 1529–1533 (1981).
Storb, R., Weiden, P. L., Graham, T. C., Lerner, K. G. & Thomas, E. D. Marrow grafts between unrelated dogs homozygous and identical for DLA antigens. Transplant. Proc. 9, 281–283 (1977).
Martin, P. J. et al. Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants. Bone Marrow Transplant. 3, 445–456 (1988).
Horowitz, M. M. et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75, 555–562 (1990).
Fefer, A., et al. in Cellular Immunotherapy of Cancer (eds Truitt, R. L., Gale, R. P. & Bortin, M. M.) 401–408 (Alan R. Liss, Inc., New York, 1987).
Kolb, H. J. et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76, 2462–2465 (1990).
Kolb, H. J. et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 86, 2041–2050 (1995).
Goulmy, E. Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol. Rev. 157, 125–140 (1997).
Warren, E. H., Greenberg, P. D. & Riddell, S. R. Cytotoxic T-lymphocyte-defined human minor histocompatibility antigens with a restricted tissue distribution. Blood 91, 2197–2207 (1998).
Warren, E. H., Gavin, M., Greenberg, P. D. & Riddell, S. R. Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation. Curr. Opin. Hematol. 5, 429–433 (1998).
Mutis, T. et al. Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens. Blood 93, 2336–2341 (1999).
Reisner, Y. et al. Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells. Lancet 2, 327–331 (1981).
Prentice, H. G. et al. Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet 1, 472–476 (1984).
Schmidt, G. M. et al. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants. N. Engl. J. Med. 324, 1005–1011 (1991).
Goodrich, J. M. et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N. Engl. J. Med. 325, 1601–1607 (1991).
Zaia, J. A. in Hematopoietic Cell Transplantation 2nd edn (eds Thomas, E. D., Blume, K. G. & Forman, S. J.) 560–583 (Blackwell Science, Boston, 1999).
Oudshoorn, M., van Leeuwen, A., vd Zanden, H. G. & van Rood, J. J. Bone Marrow Donors Worldwide: a successful exercise in international cooperation. Bone Marrow Transplant. 14, 3–8 (1994).
Broxmeyer, H. E. et al. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc. Natl Acad. Sci. USA 86, 3828–3832 (1989).
Gluckman, E. et al. Transplantation of umbilical cord blood in Fanconi's anemia. Nouv. Rev. Fr. Hematol. 32, 423–425 (1990).
Rubinstein, P. et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proc. Natl Acad. Sci. USA 92, 10119–10122 (1995).
Gluckman, E. et al. Outcome of cord-blood transplantation from related and unrelated donors. N. Engl. J. Med. 337, 373–381 (1997).
Juttner, C. A. et al. Early lympho-hemopoietic recovery after autografting using peripheral blood stem cells in acute non-lymphoblastic leukemia. Transplant. Proc. 20, 40–42 (1988).
Gianni, A. M. et al. Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation. Lancet 2, 580–585 (1989).
Bensinger, W. I. et al. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 85, 1655–1658 (1995).
Korbling, M. & Champlin, R. Peripheral blood progenitor cell transplantation: a replacement for marrow auto- or allografts. Stem Cells 14, 185–195 (1996).
Schmitz, N. et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet 347, 353–357 (1996).
Bensinger, W. I. et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N. Engl. J. Med. 344, 175–181 (2001).
Aversa, F. et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N. Engl. J. Med. 339, 1186–1193 (1998).
Ruggeri, L. et al. Kir epitope incompatibility in the GvH direction predicts control of leukemia relapse after mismatched hematopoietic transplantation. Bone Marrow Transplant. 27 (Suppl. 1), S11 (2001).
Ruggeri, L. et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 94, 333–339 (1999).
Slavin, S. et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91, 756–763 (1998).
Giralt, S. et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89, 4531–4536 (1997).
McSweeney, P. et al. Outpatient allografting with minimally myelosuppressive, immunosuppressive conditioning of low–dose TBI and postgrafting cyclosporine (CSP) and mycophenolate mofetil (MMF). Blood 94 (Suppl. 1), A393 (1999).
Feinstein, L. et al. Nonmyeloablative hematopoietic cell transplantation: replacing high-dose cytotoxic therapy by the graft-versus-tumor effect. Ann. NY Acad. Sci. 938, 328–339 (2001).
McSweeney, P. A. et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97, 3390–3400 (2001).
Khouri, I. F. et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J. Clin. Oncol. 16, 2817–2824 (1998).
Storb, R., Yu, C. & McSweeney, P. in Hematopoietic Cell Transplantation 2nd edn (eds Thomas, E. D., Blume, K. G. & Forman, S. J.) 287–295 (Blackwell Science, Boston, 1999).
Storb, R. et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 89, 3048–3054 (1997).
Storb, R. et al. Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation. Blood 94, 1131–1136 (1999).
Storb, R. et al. Stable mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosuppression after marrow transplant. Blood 94, 2523–2529 (1999).
Appelbaum, F. R. Haematopoietic cell transplantation as immunotherapy. Nature 411, 385–389 (2001).
Shipp, M. A. et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nature Med. 8, 68–74 (2002).
Lan, F. et al. Predominance of NK1.1+TCR αβ+ or DX5+TCR αβ+ T cells in mice conditioned with fractionated lymphoid irradiation protects against graft-versus-host disease: 'natural suppressor' cells. J. Immunol. 167, 2087–2096 (2001).
Taylor, P. A., Noelle, R. J. & Blazar, B. R. CD4+CD25+ immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade. J. Exp. Med. 193, 1311–1318 (2001).
Fowler, D. H. & Gress, R. E. Th2 and Tc2 cells in the regulation of GVHD, GVL, and graft rejection: considerations for the allogeneic transplantation therapy of leukemia and lymphoma. Leuk. Lymphoma 38, 221–234 (2000).
Bortin, M. M. A compendium of reported human bone marrow transplants. Transplantation 9, 571–587 (1970).
Vos, O., Davids, J. A. G., Weyzen, W. W. H. & van Bekkum, D. W. Evidence for cellular hypothesis in radiation protection by bone marrow cells. Acta Physiol. Pharmacol. Neerl. 4, 482–486 (1956).
van Bekkum, D. W., Vos, O. & Weyzen, W. W. H. Homo- et hétérogreffe tissues hématopoiétiques chez la souris. Rev. Hémat. 11, 477–485 (1956).
Billingham, R. E. & Brent, L. Quantitative studies on tissue transplantation immunity. IV. Induction of tolerance in newborn mice and studies on the phenomenon of runt disease. Phil. Trans. R. Soc. Lond. B 242, 477 (1959).
Uphoff, D. E. Genetic factors influencing irradiation protection by bone marrow. I. The F1 hybrid effect. J. Natl Cancer Inst. 19, 123–125 (1957).
Ferrebee, J. W., Lochte, H. L. Jr, Jaretzki, A., Sahler, O. D. & Thomas, E. D. Successful marrow homograft in the dog after radiation. Surgery 43, 516–520 (1958).
Goodman, J. W. & Hodgson, G. S. Evidence for stem cells in the peripheral blood of mice. Blood 19, 702–714 (1962).
Good, R. A. et al. The role of thymus in development of immunologic capacity in rabbits and mice. J. Exp. Med. 116, 773–796 (1962).
Miller, J. F. Immunity and the thymus. Lancet 1, 43–45 (1963).
Cooper, M. D., Perey, D. Y., Peterson, R. D. A., Gabrielsen, A. E. & Good, R. A. in Immunologic Deficiency Disease in Man (eds Bergsma, D. & Good, R. A.) 175–197 (Lea & Febiger, Philadelphia, 1968).
Schwartz, R. S. & Beldotti, L. Malignant lymphomas following allogeneic disease: transition from an immunological to a neoplastic disorder. Science 149, 1511–1514 (1965).
Malnin, T. I., Perry, V. P., Kerby, C. C. & Dolan, M. F. Peripheral leukocyte infusion into lethally irradiated guinea pigs. Blood 25, 693–702 (1996).
Epstein, R. B., Graham, T. C., Buckner, C. D., Bryant, J. & Thomas, E. D. Allogeneic marrow engraftment by cross circulation in lethally irradiated dogs. Blood 28, 692–707 (1966).
Steinmuller, D. & Motulsky, A. G. Treatment of hereditary spherocytosis in peromyscus by radiation and allogeneic bone marrow transplantation. Blood 29, 320–330 (1967).
Boak, J. L., Fox, M. & Wilson, R. E. Activity of lymphoid tissues from antilymphocyte-serum-treated mice. Lancet 1, 750–752 (1967).
Brent, L., Courtenay, T. & Gowland, G. Immunological reactivity of lymphoid cells after tretment with anti-lymphocytic serum. Nature 215, 1461–1464 (1967).
Graw, R. G. Jr et al. Bone marrow transplantation from HL-A-matched donors to patients with acute leukemia. Toxicity and antileukemic effect. Transplantation 14, 79–90 (1972).
Bortin, M. M., Rimm, A. A., Saltzstein, E. C. & Rodey, G. E. Graft versus leukemia. III. Apparent independent antihost and antileukemic activity of transplanted immunocompetent cells. Transplantation 16, 182–188 (1973).
Truitt, R. L., Johnson, B. D., McCabe, C. M. & Weiler, M. B. Graft versus Leukemia in Graft-vs-Host Disease 2nd edn (eds Ferrara, J. L. M., Deeg, H. J. & Burakoff, S. J.) 385–423 (Marcel Dekker, Inc., New York, 1997).
Zinkernagel, R. & Doherty, P. C. MCH-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction specificity, function and responsiveness. Adv. Immunol. 27, 51–177 (1979).
Fefer, A. et al. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N. Engl. J. Med. 300, 333–337 (1979).
Storb, R. et al. Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients. Blood 59, 236–246 (1982).
Clift, R. A. et al. Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation. Lancet 2, 621–623 (1982).
Goldman, J. M. et al. Marrow transplantation for patients in the chronic phase of chronic granulocytic leukaemia. Lancet 2, 623–625 (1982).
The transfer of haematopoietic cells that are anti-genically distinct or genetically different from one member of a species to another individual of the same species (such as from sister to brother or from an unrelated donor to a recipient).
A T-cell state of unresponsiveness, in which they cannot be activated by antigen.
- AUTOLOGOUS TRANSPLANT
The removal, storage and re-infusion of a patient's own haematopoietic stem cells.
- BONE-MARROW APLASIA
Lack of cellular development in the bone marrow.
- CD34+ CELLS
The CD34+ compartment constitutes a heterogeneous population of haematopoietic cells (approximately 1–4% of nucleated marrow and 0.1–0.2%of peripheral blood cells), which not only includes more committed lineage-restricted progenitors, but also primitive uncommitted progenitors that are capable of initiating long-term reconstitution of haematopoiesis.
- GRAFT-VERSUS-HOST DISEASE
A toxic reaction that is mediated by donor-derived T lymphocytes within the graft towards the recipient's organs. The attack is usually directed toward the skin, gut, liver and haematopoietic cells.
- GRAFT-VERSUS-TUMOUR EFFECT
Killing of cancer cells that is mediated by the transplanted T lymphocyte cells or their progeny.
- HAEMATOPOIETIC STEM CELL
A primitive and immature cell of the haematopoietic system that has the capacity to give rise to all the cells of the blood system, as well as the ability to self-renew. Allogeneic haematopoietic stem-cell transplantation involves the transfer of both immature and mature blood cells from the bone marrow, peripheral blood or cord blood from one individual to another.
In the absence of immunosuppressive drugs, transplantation of haematopoietic cells between two dissimilar individuals universally results in an immune reaction that leads to graft rejection. This reactivity results from differences in cell-surface determinants, such as histocompatibility antigens between the transplant donor and the host. Histocompatibility is detemined by the presence of compatible human leukocyte antigens (HLA) that are present on the surface of cells.
- MINOR HISTOCOMPATIBILITY ANTIGENS
Cellular proteins encoded by polymorphic genes that are differentially expressed on haematopoietic cells.
- MIXED CHIMERISM
The presence of blood cells of both donor and host in origin within the recipient of the haematopoietic stem-cell transplant. Chimerism is operationally defined as the presence of 2.5–97.5% cells of donor or host origin, as dictated by the sensitivity of the assay that is used to detect chimerism.
(Or non-myeloablative). Minimally bone-marrow suppressive.
- SYNGENEIC TRANSPLANT
Transfer of haematopoietic cells between individuals who have identical genotypes (such as twins).
- TOTAL BODY IRRADIATION
(TBI). Exposure of the entire body to radiant energy (external beam γ-irradiation) for therapeutic purposes.
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Little, MT., Storb, R. History of haematopoietic stem-cell transplantation. Nat Rev Cancer 2, 231–238 (2002). https://doi.org/10.1038/nrc748
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