Treatment of relapse after allogeneic bone marrow transplantation

  • Sergio A. Giralt
  • Koen Van Besien
Part of the Cancer Treatment and Research book series (CTAR, volume 84)


Disease relapse after allogeneic bone marrow transplantation (BMT) for hematologic malignancies remains the single most important cause of treatment failure [1–4]. Improvements in supportive care, prophylaxis of graft versus host disease (GVHD), and treatment of infectious complications have resulted in a decrease in transplant-related mortality during the years. However, modifications in the conditioning regimen and other strategies to prevent relapse have failed, and the relapse rate after allogeneic transplant has remained constant throughout the years [5,6].


Bone Marrow Transplantation Chronic Myeloid Leukemia Acute Myelogenous Leukemia Graft Versus Host Disease Allogeneic Bone Marrow Transplantation 
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.
    Bortin M, Horowitz M, Rimm A (1992). Increasing utilization of allogeneic bone marrow transplantation: results of the 1988–1990 survey. Ann Intern Med 116:505.PubMedGoogle Scholar
  2. 2.
    Champlin R, McGlave P (1994). Allogeneic bone marrow transplantation for chronic myelogenous leukemia. In Forman S, Blume K, Thomas E (eds), Bone Marrow Transplantation. Blackwell Scientific Publications: Boston, pp. 595–606.Google Scholar
  3. 3.
    Long G, Blume K (1994). Allogeneic bone marrow transplantation for acute myeloid leukemia. In Forman S, Blume K, Thomas E (eds), Bone Marrow Transplantation. Blackwell Scientific Publications: Boston, pp. 607–618.Google Scholar
  4. 4.
    Chao N, Forman S (1994). Allogeneic bone marrow transplantation for acute lymphoblastic leukemia. In Forman S, Blume K, Thomas E (eds), Bone Marrow Transplantation. Blackwell Scientific Publications: Boston, pp. 618–628.Google Scholar
  5. 5.
    Bortin M, Horowitz M, Gale R, Barrett J, Champlin R, Dicke K, Gluckman E, Kolb H, Marmont A, Mrsic M, Sobocinski K, Weiner R, Rimm A (1992). Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s. JAMA 268:607.PubMedCrossRefGoogle Scholar
  6. 6.
    Aurer I, Gale RP (1991) Are new conditioning regimens for transplants in acute myelogenous leukemia better? Bone Marrow Transplant 7:255–261.PubMedGoogle Scholar
  7. 7.
    Frassoni F, Barrett J, Granena A, Ernst P, Garthon G, Kolb H, Prentice H, Vernant J, Zwaan E, Gratwohl A (1988). Relapse after allogeneic bone marrow transplantation for acute leukemia. A survey of the EBMTR of 117 cases. Br J Hematol 70:317.CrossRefGoogle Scholar
  8. 8.
    Mortimer J, Binder M, Schulman S, Appelbaum F, Buckner C, Cliff R, Sanders J, Storb R, Thomas E (1989). Relapse of acute leukemia after marrow transplantation. Natural history and results of subsequent therapy. J Clin Oncol 7:50.PubMedGoogle Scholar
  9. 9.
    Arcese W, Goldman J, Arcangelo E, Schattenberg A, Nardi A, Apperley J, Frassoni F, Aversa F, Prentice H, Ljungman P, Ferrant A, Marosis C, Sayer H, Niederwieser D, Arnold R, Bandini G, Carreras E, Parker A, Frappaz D, Mandelli F, Gratwohl A, for the Chronic Leukemia Working Party of the European Bone Marrow Transplantation Group (1993). Outcome of patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Blood 82:3211.PubMedGoogle Scholar
  10. 10.
    Arthur C, Apperley J, Guo A, Rassool F, Gao L, Goldman J (1988). Cytogenetic events after bone marrow transplantation for chronic myeloid leukemia in chronic phase. Blood 71:1179.PubMedGoogle Scholar
  11. 11.
    Hughes T, Economou K, Mackinnon S, Ulitos M, Arthur C, Guo A, Rassool F, Apperley J, Hows J, Goldman J (1989). Slow evolution of chronic myeloid leukemia relapsing after bone marrow transplantation with T-cell depleted donor marrow. Br J Hematol 73:462.CrossRefGoogle Scholar
  12. 12.
    Odom L, Githers J, Morse H, Sharna B, August c, Humbert J, Peakman D, Rosnak S, Johnson F (1978). Remission of relapsed leukemia during a graft-versus-host reaction. A graft-versus-leukemia reaction in man? Lancet 2:537.PubMedCrossRefGoogle Scholar
  13. 13.
    Higano C, Brixey M, Bryant E, Durman D, Doney K, Sullivan K, Singer J (1990). Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marror transplantation. A case report of a probable graft-versus-leukemia effect. Transplantation 50:175.PubMedCrossRefGoogle Scholar
  14. 14.
    Collins R, Rogers Z, Bennett M, Kumar V, Nikein A, Fay J (1992). Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppresion. Bone Marrow Transplant 10:391.PubMedGoogle Scholar
  15. 15.
    Flowers M, Clift R, Schoch G, Sullivan K, Martin P (1994). Discontinuation of cyclosporine to induce a graft-versus-leukemia effect in patients with cytogenetic relapse after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Blood 84 (Suppl 1):540a.Google Scholar
  16. 16.
    Bostrom B, Woods W, Nesbit M, Krivit W, Kersey J, Weisdorf D, Haake R, Goldman A, Ramsey N (1987). Succesful reinduction of patients with acute lymphoblastic leukemia who relapse following bone marrow transplantation. J Clin Oncol 5:376.PubMedGoogle Scholar
  17. 17.
    Barrett A, Tew C, Joshi R (1985). How should acute lymphoblastic leukemia relapsing after bone-marrow transplantation be treated? Lancet 1:1188.PubMedCrossRefGoogle Scholar
  18. 18.
    Barrett A, Joshi R, kencha J, Phillips R, Ashford R, Shaw P, Hugh-Jones K, Hobbs J (1986). Prediction and prevention of relapse of acute lymphoblastic leukemia after bone marrow transplantation. Br J Haematol 64:179.PubMedCrossRefGoogle Scholar
  19. 19.
    Doney K, Fisher L, Appelbaum F, Buckner C, Storb R, Singer J, Fefer A, Anasetti C, Beatty P, Bensinger W, Clift R, Hansen J, Hill R, Loughran T, Martin P, Petersen F, Sanders J, Sullivan K, Stewart P, Weiden P, Witherspoon R, Thomas E (1991). Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation: multivariate analysis of factors affecting acute graft-versus-host disease, relapse, and relapse free survival. Bone Marrow Transplant 7:453.PubMedGoogle Scholar
  20. 20.
    Chak L, Sapozink M, Cox R (1983). Extramedullary lesions in non-lymphocytic leukemia results of radiation therapy. Int J Radiat Oncol Biol Phys 9:1173.PubMedCrossRefGoogle Scholar
  21. 21.
    Bowman W, Aur R, Hustu H, Rivera G (1984). Isolated testicular relapse in acute lymphocytic leukemia of childhood: categories and influence on survival. J Clin Oncol 2:924.PubMedGoogle Scholar
  22. 22.
    Wright S, Thomas E, Buckner C, Clift R, Fefer A, Neiman P, Storb R (1976). Experience with second marrow transplants. Exp Hematol 4:221.PubMedGoogle Scholar
  23. 23.
    Champlin R, Ho W, Lenarsky C, Mitsuyasu R, Feig S, Gale R (1985). Succesful second bone marrow transplantation for AML or ALL. Transplant Proc 17:496.Google Scholar
  24. 24.
    Sanders J, Buckner C, Clift R, Fefer A, McGuffin R, Storb R, Appelbaum F, Bensinger W, Beatty P, Doney K, Durnam D, Martin P, Sullivan K, Stewart P, Witherspoon R, Thomas E (1988). Second marrow transplants in patients with leukemia who relapse after allogeneic marrow transplantation. Bone Marrow Transplant 3:11.PubMedGoogle Scholar
  25. 25.
    Radich J, Sanders J, Buckner C, Martin P, Petersen F, Bensinger W, McDonald G, Mori M, Scoch G, Hansen J (1993). Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total body irradiation containing regimens. J Clin Oncol 11:304.PubMedGoogle Scholar
  26. 26.
    Stern L, Landan M, Feig S, Gajewski J (1992). Outcome of second bone marrow transplants. Blood 80:334a.Google Scholar
  27. 27.
    Wagner J, Vogelsang G, Zehnbauer B, Griffen C, Shan N, Santos G (1992). Relapse of leukemia after bone marrow transplantation: effect of second myeloablative therapy. Bone Marrow Transplant 9:205.PubMedGoogle Scholar
  28. 28.
    Barrett A, Locatelfi F, Treleaven J, Gratwohl A, Szydlo R, Zwaan F (1991). Second transplants for leukemic relapse after bone marrow transplantation: high early mortality but favorable effect of chronic GVHD on continued remission. Br J Hematol 78:561.CrossRefGoogle Scholar
  29. 29.
    Mrsic M, Horowitz M, Atkinson K, Biggs J, Champlin R, Ehninger G, Gajewski J, Gale R, Herzig R, Prentice H, Rozman C, Sobocinski K, Speck B, Bortin M (1992). Second HLA-identical sibling transplants for leukemia recurrence. Bone Marrow Transplant 9:269.PubMedGoogle Scholar
  30. 30.
    Blume K, Forman S (1987). High dose busulfan/etoposide as a preparatory regimen for second bone marrow transplants in hematologic malignancies. Blut 55:49.PubMedCrossRefGoogle Scholar
  31. 31.
    Atkinson K, Biggs J, Concannon A, Dodds A, Dale B, Norman J (1986). Second marrow transplants for recurrence of hematological malignancy. Bone Marrow Transplant 1:159.PubMedGoogle Scholar
  32. 32.
    Nemunaitis J, Albo V, Zeigler Z, Shadduck R, Rosenfeld C (1993). Reduction of allogeneic transplant morbidity by combining peripheral blood and bone marrow progenitor cells. Leuk Lymphoma 10:405.PubMedCrossRefGoogle Scholar
  33. 33.
    Russell N, Hunter A, Rogers S, Hanley J, Anderson D (1993). Peripheral blood stem cells as an alternative to marrow for allogeneic transplantation. Lancet 341:1482.PubMedCrossRefGoogle Scholar
  34. 34.
    Korbling M, Przepiorka D, Engel H, van Besien K, Giralt S, Anderson B, Huh Y, Deisseroth A, Andreeff M, Champlin R (1994). Allogeneic blood stem cell transplantation (allo-pbsct) in 9 patients with refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. Blood 84 (Suppl 1):396a.Google Scholar
  35. 35.
    Giralt S, Escudier S, Kantarjian H, Deisseroth A, Freireich E, Andersson B, O’Brien S, Andreef M, Fisher H, Cork A, Hirsch-Ginsbery C, Trujillo J, Stass S, Champlin R (1993). Treatment with filgrastim for relapse of leukemia and myelodysplasia after allogeneic bone marrow transplantation. Preliminary observations. N Engl J Med 329:357.CrossRefGoogle Scholar
  36. 36.
    Giralt S, Hester J, Talpaz M, Kantarjian H, Van Besien K, Andersson B, Chan K, Gajewski J, Mehra R, Przepiorka D, Deisseroth A, Champlin R (1994). Cytokine therapy for patients relapsing after allogeneic bone marrow transplantation. J Cell Biochem (Suppl 18B):88a.Google Scholar
  37. 37.
    Tafuri A, Andreeff M (1990). Kinetic rationale for cytokine-induced recruitment of myeloblastic leukemia followed by cycle-specific chemotherapy in vitro. Leukemia 4:826.PubMedGoogle Scholar
  38. 38.
    Baron S, Tyring S, Fleischmann W, Coppenhaver D, Niesen D, Kumpel G, Stanton J, Hughes T (1991). The interferons. Mechanism of action and clinical applications. JAMA 266:1375.PubMedCrossRefGoogle Scholar
  39. 39.
    Talpaz M, Kantarjian H, Kurzroch R, Trujillo J, Gutterman J (1991). Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann Intern Med 114:532.PubMedGoogle Scholar
  40. 40.
    Arcese W, Mauro F, Alimena G, Lo Coco F, De Cuia M, Screnci M, Iori A, Montefusco E, Mandelli F (1991). Interferon therapy for Ph positive CML patients relapsing after T-cell-depleted allogeneic bone marrow transplantation. Bone Marrow Transplant 5:309.Google Scholar
  41. 41.
    Higano C, Raskind W, Singer J (1992). Use of α-interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation. Blood 80:1437.PubMedGoogle Scholar
  42. 42.
    Rosenberg S, Grimm E, McGrogan M, Doyle M, Kawasaki E, Koths K, Marks D (1984). Biological activity of recombinant human interleukin-2. Science 223:1412.PubMedCrossRefGoogle Scholar
  43. 43.
    Oshimi K, Oshimi Y, Akutsu M, Takei Y, Saito H, Okada M, Mizoguchi H (1986). Cytotoxicity of interleukin-2 activated lymphocytes for leukemia and lymphoma cells. Blood 68:938.PubMedGoogle Scholar
  44. 44.
    Maraninchi D, Blaise D, Viens P, Brandely M, Olive D, Lopez M, Sainty D, Marit G, Stoppa A, Reiffers J, Gratecos N, Bertau-perez P, Mannoni P, Mawas C, Hercend T, Sebahoun G, Carcassonne Y (1991). High dose recombinant interleukin-2 and acute myeloid leukemias in relapse. Blood 78:218.Google Scholar
  45. 45.
    Foa R, Meloni G, Tosti S, Novarino A, Fern S, Gavosta F (1991). Treatment of acute myelogenous leukemia patients with recombinant interleukin-2: a pilot study. Br J Hematol 77:491.CrossRefGoogle Scholar
  46. 46.
    Kolb H, Mittermuller J, Clemm C, Holler E, Ledrerose G, Brehm G, Heim M, Wilmanns W (1990). Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76:2462.PubMedGoogle Scholar
  47. 47.
    Frassoni F, Fagioli F, Sessarego M, Figari F, Valbonesi M, Bacigalupo A (1992). The effect of donor leucocyte infusion in patients with leukemia following allogeneic bone marrow transplantation. Exp Hematol 20:712a.Google Scholar
  48. 48.
    Porter D, Roth M, McGarigle C, Ferrara J, Antin J (1994). Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med 330:100.PubMedCrossRefGoogle Scholar
  49. 49.
    Drobyski W, Keever C, Roth M, Koethe S, Hanson G, McFadden P, Gottschal J, Ash R, Van Tuinen P, Horowitz M, Flomenberg N (1993). Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood 82:2310.PubMedGoogle Scholar
  50. 50.
    Szer J, Grigg A, Phillips G, Sheridan W (1993). Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukemia following allogeneic BMT. Bone Marrow Transplant 11:109.PubMedGoogle Scholar
  51. 51.
    Helg C, Roux E, Beris P, Cabrol C, Wacker P, Darbellay R, Wyss M, Jeannet M, Chapuis B, Roosnek E (1993). Adoptive immunotherapy for recurrent CML after BMT. Bone Marrow Transplant 12:125.PubMedGoogle Scholar
  52. 52.
    van Rhee F, Lin F, Cullis J, Spencer A, Cross N, Chase A, Garicochea B, Bungey J, Barrett J, Goldman J (1994). Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse. Blood 83:3377.PubMedGoogle Scholar
  53. 53.
    Bar B, Schattenberg A, Mensink E, Geurts Van Kessel A, Smetsers T, Knops G, Linders E, De Witte T (1993). Donor leukocyte infusions for chronic myelogenous leukemia after allogeneic bone marrow transplantation. J Clin Oncol 11:513.PubMedGoogle Scholar
  54. 54.
    Hertenstein B, Wiesneth M, Novotny J, Bunjes D, Stefanic M, Heinze B, Hübner G, Heimpel H, Arnold R (1993). Interferon-α and donor buffy coat transfusions for treatment of relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Transplantation 56:1114–1118.PubMedCrossRefGoogle Scholar
  55. 55.
    Kolb H, de Witte T, Mittermuller J, Hertenstein B, Goldman J, Ljungman P, Verdonck L, Holler E, Thalmeier K, Bartram C for the EBMT Chronic Leukemia Working Party (1993). Graft-versus-leukemia effect of donor buffy coat transfusions on recurrent leukemia after marrow transplantation. Blood 82 (Suppl 1):214a.Google Scholar
  56. 56.
    Antin J (1993). Graft-versus-leukemia: no longer an epiphenomenon. Blood 82:2273.PubMedGoogle Scholar
  57. 57.
    Faber L, van Luxemberg-Heijs S, Willemze R, Falkenburg J (1992). Generation of leukemia-reactive cytotoxic T lymphocyte clones from the HLA-identical bone marrow donor of a patient with leukemia. J Exp Med 176:1283–1289.PubMedCrossRefGoogle Scholar
  58. 58.
    Sosman J, Oettel K, Smith S, Hank J, Fisch P, Sondel P (1990). Specific recognition of human leukemic cells by allogeneic T-cells: II. Evidence for HLA-D restricted determinants on leukemic cells that are crossreactive with determinants present on unrelated non leukemic cells. Blood 75:2005–2016.PubMedGoogle Scholar
  59. 59.
    Jiang Y, Kanfer E, MacDonald D, Cullis J, Goldman J, Barrett A (1991). Graft versus leukemia following allogeneic bone marrow transplantation: emergence of cytotoxic T lymphocytes reacting to host leukemia cells. Bone Marrow Transplant 8:253–258.PubMedGoogle Scholar
  60. 60.
    Jiang Y, Cullis J, Kanfer E, Goldman J, Barrett A (1993). T cell and NK cell mediated graft-versus-leukemia reactivity following donor buffy coat transfusion to treat relapse after marrow transplantation for chronic myeloid leukemia. Bone Marrow Transplant 11:133–138.PubMedGoogle Scholar
  61. 61.
    Hercend T, Takvorian T, Nowill A, et al. (1986). Characterization of natural killer cells with anti-leukemia activity following allogeneic bone marrow transplantation. Blood 67:301–305.Google Scholar
  62. 62.
    Hoffmann T, Theobald M, Bunjes D, Weiss M, Heimpel H, Heit W (1993). Frequency of bone marrow T-cells responding to HLA-identical non-leukemic and leukemic stimulator cells. Bone Marrow Transplant 12:1.PubMedGoogle Scholar
  63. 63.
    Mackinnon S, Papadopoulos E, Carabasi M, Reich L, Collins N, Boulad F, Castro-Malaspina H, Childs B, Gillio A, Kernan N, Small T, Young J, O’Reilly R (1994). Adoptive immunotherapy using escalating doses of donor leukocytes for relapsed chronic myeloid leukemia following allogeneic bone marrow transplantation. Blood 84 (Suppl 1):538a.Google Scholar
  64. 64.
    Giralt S, Hester J, Huh Y, Hirsch-Ginsberg C, Rondón, Guo J, Lee M, Gajewski J, Talpaz M, kantarjian H, Fischer H, Deisseroth A, Champlin R (1994). CD8+ depleted donor lymphocyte infusion for relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT): graft vs leukemia without graft vs host disease (GVHD). Blood 84 (Suppl 1):538a.Google Scholar
  65. 65.
    Collins R, Wolff S, List A, Christiansen N, Pineiro L, Greer J, Goodman S, Dalton W, Gonzalez G, Herzig G, Phillips G, Fay J (1994). Prospective multicenter trial of donor buffy coat infusion for relapsed hematologic malignancy post allogeneic bone marrow transplantation (BMT). Blood 84 (Suppl 1):333a.Google Scholar
  66. 66.
    Verfaillie C, Weisdorf D, McGlave P, Vercellotti G, Enright H, Burns L, Miller J (1994). High dose mononuclear cell infusion in post transplant relapsed AML/MDS. Blood 84 (Suppl 1):333a.Google Scholar
  67. 67.
    Slavin S, Nagler A (1991). New developments in bone marrow transplantation. Curr Opin Oncol 3:254.PubMedCrossRefGoogle Scholar
  68. 68.
    Klingemann H, Phillips G (1991). Immunotherapy after bone marrow transplantation. Bone Marrow Transplant 8:73.PubMedGoogle Scholar
  69. 69.
    Slavin S, Weiss L, Ackerstein A, Vourka-Karussis U, Morecki S, Or R, Nagler A, Kapelushnik J, Delukina M, Drakos P, Naparstek E (1991). Prevention and treatment of relapse by bone marrow transplantation. Bone Marrow Transplant 7 (Suppl 1):54.Google Scholar
  70. 70.
    Appelbaum F, Matthews D, Eary J, Badger C, Kellog M, Preis O, Martin P, Fisher D, Nelp W, Thomas E (1992). The use of radiolabeled anti CD-33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. Transplantation 54:829.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1996

Authors and Affiliations

  • Sergio A. Giralt
  • Koen Van Besien

There are no affiliations available

Personalised recommendations