Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Bone Marrow Transplantation volume 41, pages 495–503 (2008)Cite this article

Abstract

The management of acute leukaemia which relapses following an allogeneic stem cell transplant remains a major challenge. In this review we summarize the outcomes of the currently available treatment modalities and discuss emerging novel approaches.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Kumar L . Leukemia: management of relapse after allogeneic bone marrow transplantation. J Clin Oncol 1994; 12: 1710–1717.

    CAS  PubMed  Google Scholar 

  2. Frassoni F, Barrett AJ, Granena A, Ernst P, Garthon G, Kolb HJ et al. Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the E.B.M.T. of 117 cases. Br J Haematol 1988; 70: 317–320.

    CAS  PubMed  Google Scholar 

  3. Mortimer J, Blinder MA, Schulman S, Appelbaum FR, Buckner CD, Clift RA et al. Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy. J Clin Oncol 1989; 7: 50–57.

    CAS  PubMed  Google Scholar 

  4. Doney K, Fisher LD, Appelbaum FR, Buckner CD, Storb R, Singer J et al. 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 1991; 7: 453–459.

    CAS  PubMed  Google Scholar 

  5. Kikushige Y, Takase K, Sata K, Aoki K, Numata A, Miyamoto T et al. Repeated relapses of acute myelogenous leukemia in the isolated extramedullary sites following allogeneic bone marrow transplantations. Intern Med 2007; 46: 1011–1014.

    PubMed  Google Scholar 

  6. Lawler M, Locasciulli A, Longoni D, Schiro R, McCann SR . Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia. Bone Marrow Transplant 2002; 29: 453–456.

    CAS  PubMed  Google Scholar 

  7. Hambach L, Eder M, Dammann E, Battmer K, Stucki A, Heil G et al. Donor cell-derived acute myeloid leukemia developing 14 months after matched unrelated bone marrow transplantation for chronic myeloid leukemia. Bone Marrow Transplant 2001; 28: 705–707.

    CAS  PubMed  Google Scholar 

  8. Knechtli CJ, Goulden NJ, Hancock JP, Grandage VL, Harris EL, Garland RJ et al. Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia. Blood 1998; 92: 4072–4079.

    CAS  PubMed  Google Scholar 

  9. Bader P, Hancock J, Kreyenberg H, Goulden NJ, Niethammer D, Oakhill A et al. Minimal residual disease (MRD) status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL. Leukemia 2002; 16: 1668–1672.

    CAS  PubMed  Google Scholar 

  10. van der Velden VH, Joosten SA, Willemse MJ, van Wering ER, Lankester AW, van Dongen JJ et al. Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia. Leukemia 2001; 15: 1485–1487.

    CAS  PubMed  Google Scholar 

  11. Schilham MW, Balduzzi A, Bader P . Is there a role for minimal residual disease levels in the treatment of ALL patients who receive allogeneic stem cells? Bone Marrow Transplant 2005; 35 (Suppl 1): S49–S52.

    PubMed  Google Scholar 

  12. Miglino M, Berisso G, Grasso R, Canepa L, Clavio M, Pierri I et al. Allogeneic bone marrow transplantation (BMT) for adults with acute lymphoblastic leukemia (ALL): predictive role of minimal residual disease monitoring on relapse. Bone Marrow Transplant 2002; 30: 579–585.

    CAS  PubMed  Google Scholar 

  13. Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ et al. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2005; 106: 458–463.

    CAS  PubMed  Google Scholar 

  14. Laczika K, Mitterbauer G, Mitterbauer M, Knobl P, Schwarzinger I, Greinix HT et al. Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBFbeta/MYH11 RT–PCR: implications for a monitoring schedule and for treatment decisions. Leuk Lymphoma 2001; 42: 923–931.

    CAS  PubMed  Google Scholar 

  15. Au WY, Lie AK, Lee CK, Liang R, Kwong YL . Donor lymphocyte infusion induced molecular remission in relapse of acute myeloid leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 23: 1201–1203.

    CAS  PubMed  Google Scholar 

  16. Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F et al. Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia. Blood 2007; 109: 5063–5064.

    CAS  PubMed  Google Scholar 

  17. Campana D, Pui CH . Detection of minimal residual disease in acute leukemia: methodologic advances and clinical significance. Blood 1995; 85: 1416–1434.

    CAS  PubMed  Google Scholar 

  18. Bader P, Niethammer D, Willasch A, Kreyenberg H, Klingebiel T . How and when should we monitor chimerism after allogeneic stem cell transplantation? Bone Marrow Transplant 2005; 35: 107–119.

    CAS  PubMed  Google Scholar 

  19. Keil F, Prinz E, Moser K, Mannhalter C, Kalhs P, Worel N et al. Rapid establishment of long-term culture-initiating cells of donor origin after nonmyeloablative allogeneic hematopoietic stem-cell transplantation, and significant prognostic impact of donor T-cell chimerism on stable engraftment and progression-free survival. Transplantation 2003; 76: 230–236.

    CAS  PubMed  Google Scholar 

  20. Perez-Simon JA, Caballero D, Diez-Campelo M, Lopez-Perez R, Mateos G, Canizo C et al. Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation. Leukemia 2002; 16: 1423–1431.

    CAS  PubMed  Google Scholar 

  21. Fernandez-Aviles F, Urbano-Ispizua A, Aymerich M, Colomer D, Rovira M, Martinez C et al. Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood. Leukemia 2003; 17: 613–620.

    CAS  PubMed  Google Scholar 

  22. Zeiser R, Spyridonidis A, Wasch R, Ihorst G, Grullich C, Bertz H et al. Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation. Leukemia 2005; 19: 814–821.

    CAS  Google Scholar 

  23. Thiede C, Lutterbeck K, Oelschlagel U, Kiehl M, Steudel C, Platzbecker U et al. Detection of relapse by sequential monitoring of chimerism in circulating CD34+ cells. Ann Hematol 2002; 81 (Suppl 2): S27–S28.

    PubMed  Google Scholar 

  24. Mattsson J, Uzunel M, Tammik L, Aschan J, Ringden O . Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation. Leukemia 2001; 15: 1976–1985.

    CAS  PubMed  Google Scholar 

  25. Zetterquist H, Mattsson J, Uzunel M, Nasman-Bjork I, Svenberg P, Tammik L et al. Mixed chimerism in the B cell lineage is a rapid and sensitive indicator of minimal residual disease in bone marrow transplant recipients with pre-B cell acute lymphoblastic leukemia. Bone Marrow Transplant 2000; 25: 843–851.

    CAS  Google Scholar 

  26. Hubmann M, Burkhardt R, Franke G, Cross M, Scholz M, Leiblein S et al. CD34+ donor chimerism and Wilms tumor gene 1 (WT1) expression provide an early indication of relapse in patients with acute leukemias and MDS after hematopoietic cell transplantation (HCT) with reduced-intensity conditioning (abstract). Blood 2006; 108: 548.

    Google Scholar 

  27. Barge RMY, Steel E, Starrenburg I, Beaumont F, Smit WM, Schaafsma MR et al. Adoptive immunotherapy with donor lymphocyte infusions after T-cell depleted allogeneic stem cell transplantation for patients with acute myeloid leukemia (abstract). Blood 2005; 106: 2014.

    Google Scholar 

  28. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2003; 9: 320–329.

    PubMed  Google Scholar 

  29. Marijt EWA, Von Dem Borne PA, Renee MY, Barge RMY, Deutz PP, Beaumont MF et al. Donor lymphocyte infusion (DLI) for mixed chimerism 6 months after T cell depleted allogeneic stem cell transplantation (TCD alloSCT) may prevent relapse (abstract). Blood 2006; 108: 3674.

    Google Scholar 

  30. Shaw BE, Byrne JL, Das-Gupta E, Carter GI, Russell NH . The impact of chimerism patterns and predonor leukocyte infusion lymphopenia on survival following T cell-depleted reduced intensity conditioned transplants. Biol Blood Marrow Transplant 2007; 13: 550–559.

    PubMed  Google Scholar 

  31. Kobbe G, Fenk R, Neumann F, Bernhardt A, Steidl U, Kondakci M et al. Transplantation of allogeneic CD34+-selected cells followed by early T-cell add-backs: favorable results in acute and chronic myeloid leukemia. Cytotherapy 2004; 6: 533–542.

    CAS  PubMed  Google Scholar 

  32. Ferra C, Rodriguez-Luaces M, Gallardo D, Encuentra M, Martin-Henao GA, Peris J et al. Individually adjusted prophylactic donor lymphocyte infusions after CD34-selected allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 28: 963–968.

    CAS  PubMed  Google Scholar 

  33. de Lima M, Bonamino M, Vasconcelos Z, Colares M, Diamond H, Zalcberg I et al. Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease. Bone Marrow Transplant 2001; 27: 73–78.

    CAS  PubMed  Google Scholar 

  34. Schaap N, Schattenberg A, Bar B, Preijers F, van de Wiel van Kemenade E, de Witte T . Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia 2001; 15: 1339–1346.

    CAS  PubMed  Google Scholar 

  35. Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 2006; 108: 1092–1099.

    CAS  PubMed  Google Scholar 

  36. Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A et al. Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 2000; 95: 67–71.

    CAS  PubMed  Google Scholar 

  37. Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, Boulad F 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 1995; 86: 1261–1268.

    CAS  PubMed  Google Scholar 

  38. Peggs KS, Thomson K, Hart DP, Geary J, Morris EC, Yong K et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. Blood 2004; 103: 1548–1556.

    CAS  PubMed  Google Scholar 

  39. Shimoni A, Kroger N, Zander AR, Rowe JM, Hardan I, Avigdor A et al. Imatinib mesylate (STI571) in preparation for allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusions in patients with Philadelphia-positive acute leukemias. Leukemia 2003; 17: 290–297.

    CAS  PubMed  Google Scholar 

  40. Soriano AO, Champlin R, McCormick G, Giralt S, Thall P, Komanduri K et al. Maintenance therapy with 5azacytidine (5-AC) after allogeneic stem cell transplantation (allo-SCT) for acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS): a dose and schedule finding study (abstract). Blood 2006; 108: 3668.

    Google Scholar 

  41. Eapen M, Giralt SA, Horowitz MM, Klein JP, Wagner JE, Zhang MJ et al. Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant. Bone Marrow Transplant 2004; 34: 721–727.

    CAS  PubMed  Google Scholar 

  42. Messori A, Bosi A, Bacci S, Laszlo D, Trippoli S, Locatelli F et al. Retrospective survival analysis and cost-effectiveness evaluation of second allogeneic bone marrow transplantation in patients with acute leukemia. Gruppo Italiano Trapianto di Midollo Osseo. Bone Marrow Transplant 1999; 23: 489–495.

    CAS  PubMed  Google Scholar 

  43. Arellano ML, Langston A, Winton E, Flowers CR, Waller EK . Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience. Biol Blood Marrow Transplant 2007; 13: 116–123.

    PubMed  Google Scholar 

  44. Bostrom B, Woods WG, Nesbit ME, Krivit W, Kersey J, Weisdorf D et al. Successful reinduction of patients with acute lymphoblastic leukemia who relapse following bone marrow transplantation. J Clin Oncol 1987; 5: 376–381.

    CAS  PubMed  Google Scholar 

  45. Czibere A, Graef T, Lind J, Gattermann N, Zohren F, Fenk R et al. 5-Azacitidine in combination with donor lymphocyte infusions for the treatment of patients with MDS or AML relapsing after allogeneic stem cell transplantation (abstract). Blood 2006; 108: 5341.

    Google Scholar 

  46. Lee KH, Lee JH, Choi SJ, Lee JH, Kim S, Seol M et al. Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course. Bone Marrow Transplant 2003; 32: 835–842.

    CAS  PubMed  Google Scholar 

  47. Owonikoko T, Agha M, Balassanian R, Smith R, Raptis A . Gemtuzumab therapy for isolated extramedullary AML relapse following allogeneic stem-cell transplant. Nat Clin Pract Oncol 2007; 4: 491–495.

    CAS  PubMed  Google Scholar 

  48. Elmaagacli AH, Beelen DW, Schaefer UW . A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 20: 1045–1055.

    CAS  PubMed  Google Scholar 

  49. Higano CS, Brixey M, Bryant EM, Durnam DM, Doney K, Sullivan KM et al. Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation. A case report of a probable graft-versus-leukemia effect. Transplantation 1990; 50: 175–177.

    CAS  PubMed  Google Scholar 

  50. Mehta J, Powles R, Kulkarni S, Treleaven J, Singhal S . Induction of graft-versus-host disease as immunotherapy of leukemia relapsing after allogeneic transplantation: single-center experience of 32 adult patients. Bone Marrow Transplant 1997; 20: 129–135.

    CAS  PubMed  Google Scholar 

  51. Porter DL, Antin JH . Donor leukocyte infusions in myeloid malignancies: new strategies. Best Pract Res Clin Haematol 2006; 19: 737–755.

    CAS  PubMed  Google Scholar 

  52. Dazzi F, Fozza C . Disease relapse after haematopoietic stem cell transplantation: risk factors and treatment. Best Pract Res Clin Haematol 2007; 20: 311–327.

    CAS  PubMed  Google Scholar 

  53. Bethge WA, Hegenbart U, Stuart MJ, Storer BE, Maris MB, Flowers ME et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood 2004; 103: 790–795.

    CAS  PubMed  Google Scholar 

  54. Lush RJ, Haynes AP, Byrne J, Cull GM, Carter GI, Pagliuca A et al. Allogeneic stem-cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH (+/− fludarabine) conditioning combined with post-transplant donor-lymphocyte infusion. Cytotherapy 2001; 3: 203–210.

    CAS  PubMed  Google Scholar 

  55. Russell NH, Byrne JL, Faulkner RD, Gilyead M, Das-Gupta EP, Haynes AP . Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation. Bone Marrow Transplant 2005; 36: 437–441.

    CAS  PubMed  Google Scholar 

  56. Collins Jr RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    PubMed  Google Scholar 

  57. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  58. Kolb HJ . Donor leukocyte transfusions for treatment of leukemic relapse after bone marrow transplantation. EBMT Immunology and Chronic Leukemia Working Parties. Vox Sang 1998; 74 (Suppl 2): 321–329.

    CAS  PubMed  Google Scholar 

  59. Carlens S, Remberger M, Aschan J, Ringden O . The role of disease stage in the response to donor lymphocyte infusions as treatment for leukemic relapse. Biol Blood Marrow Transplant 2001; 7: 31–38.

    CAS  PubMed  Google Scholar 

  60. Schmid C, Labopin M, Finke J, Ehninger G, Ringden O, Niederwieser D et al. Retrospective comparison of using or not using donor lymphocyte transfusion in the treatment of hematological relapse after allogeneic stem cell transplantation in 489 adults with acute myeloid leukemia (abstract). Blood 2004; 104: 298.

    Google Scholar 

  61. Shaw BE . Understanding the Immunogenetic and Clinical Factors Which Influence the Outcome of Haematopoietic Stem Cell Transplantation Using Unrelated Donors. University of London: London, 2004.

    Google Scholar 

  62. Levine JE, Braun T, Penza SL, Beatty P, Cornetta K, Martino R et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol 2002; 20: 405–412.

    CAS  PubMed  Google Scholar 

  63. Huff CA, Fuchs EJ, Smith BD, Blackford A, Garrett-Mayer E, Brodsky RA et al. Graft-versus-host reactions and the effectiveness of donor lymphocyte infusions. Biol Blood Marrow Transplant 2006; 12: 414–421.

    PubMed  Google Scholar 

  64. Lee JH, Lee KH, Kim S, Seol M, Kim SH, Kim WK et al. Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. Leuk Res 2001; 25: 305–312.

    CAS  PubMed  Google Scholar 

  65. Choi SJ, Lee JH, Kim S, Seol M, Lee YS, Lee JS et al. Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse. Leukemia 2004; 18: 1789–1797.

    CAS  PubMed  Google Scholar 

  66. Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik J, Or R . Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. Exp Hematol 1995; 23: 1553–1562.

    CAS  PubMed  Google Scholar 

  67. Atra A, Millar B, Shepherd V, Shankar A, Wilson K, Treleaven J et al. Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation. Br J Haematol 1997; 97: 165–168.

    CAS  PubMed  Google Scholar 

  68. Yazaki M, Andoh M, Ito T, Ohno T, Wada Y . Successful prevention of hematological relapse for a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation by donor leukocyte infusion. Bone Marrow Transplant 1997; 19: 393–394.

    CAS  PubMed  Google Scholar 

  69. Choi SJ, Lee JH, Kim S, Lee YS, Seol M, Ryu SG et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant 2005; 36: 163–169.

    CAS  PubMed  Google Scholar 

  70. Shaw BE, Marsh SG, Mayor NP, Russell NH, Madrigal JA . HLA-DPB1 matching status has significant implications for recipients of unrelated donor stem cell transplants. Blood 2006; 107: 1220–1226.

    CAS  PubMed  Google Scholar 

  71. Remberger M, Mattsson J, Hentschke P, Aschan J, Barkholt L, Svennilson J et al. The graft-versus-leukaemia effect in haematopoietic stem cell transplantation using unrelated donors. Bone Marrow Transplant 2002; 30: 761–768.

    CAS  PubMed  Google Scholar 

  72. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  73. Collins Jr RH, Goldstein S, Giralt S, Levine J, Porter D, Drobyski W et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 2000; 26: 511–516.

    PubMed  Google Scholar 

  74. Slavin S, Naparstek E, Nagler A, Ackerstein A, Samuel S, Kapelushnik J et al. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood 1996; 87: 2195–2204.

    CAS  PubMed  Google Scholar 

  75. Alyea EP, Soiffer RJ, Canning C, Neuberg D, Schlossman R, Pickett C et al. Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998; 91: 3671–3680.

    CAS  PubMed  Google Scholar 

  76. Shimoni A, Gajewski JA, Donato M, Martin T, O'Brien S, Talpaz M et al. Long-term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant 2001; 7: 568–575.

    CAS  PubMed  Google Scholar 

  77. Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Streicher H et al. Phase I study of ipilimumab (neutralizing monoclonal anti-CTLA4 antibody) to treat relapse of malignancy after allogeneic hematopoietic stem cell transplantation: evidence of tumor regression without induction of GVHD (abstract). Blood 2006; 108: 410.

    Google Scholar 

  78. Huang XJ, Liu DH, Xu LP, Chen H, Han W, Liu KY et al. Prophylactic infusion of donor granulocyte colony stimulating factor mobilized peripheral blood progenitor cells after allogeneic hematological stem cell transplantation in patients with high-risk leukemia. Leukemia 2006; 20: 365–368.

    CAS  PubMed  Google Scholar 

  79. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W . Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica 2007; 92: 414–417.

    PubMed  Google Scholar 

  80. Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J et al. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant 2006; 38: 621–627.

    CAS  PubMed  Google Scholar 

  81. Bosi A, Laszlo D, Labopin M, Reffeirs J, Michallet M, Gluckman E et al. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol 2001; 19: 3675–3684.

    CAS  PubMed  Google Scholar 

  82. Bosi A, Bacci S, Miniero R, Locatelli F, Laszlo D, Longo G et al. Second allogeneic bone marrow transplantation in acute leukemia: a multicenter study from the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO). Leukemia 1997; 11: 420–424.

    CAS  PubMed  Google Scholar 

  83. Michallet M, Tanguy ML, Socie G, Thiebaut A, Belhabri A, Milpied N et al. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de moelle (SFGM). Br J Haematol 2000; 108: 400–407.

    CAS  PubMed  Google Scholar 

  84. Pawson R, Potter MN, Theocharous P, Lawler M, Garg M, Yin JA et al. Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/− Ida) and second allogeneic stem cell transplant. Br J Haematol 2001; 115: 622–629.

    CAS  PubMed  Google Scholar 

  85. Shaw BE, Mufti GJ, Mackinnon S, Cavenagh J, Towlson K, Pearce R et al. Outcome of second allogeneic transplants using reduced intensity conditioning following relapse after an initial allogeneic transplant (abstract). Bone Marrow Transplant 2007; 39 (Suppl 1): S16.

    Google Scholar 

  86. Sica RA, Vosganian GS, Tuscano JM, Law LY, Richman CM . Reduced intensity stem cell transplant (RIST) as salvage treatment for relapse following myeloablative allogeneic transplantation in adult acute myeloid leukemia (abstract). Biol Blood Marrow Transplant 2007; 13: 133.

    Google Scholar 

  87. Devine SM, Sanborn R, Jessop E, Stock W, Huml M, Peace D et al. Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. Bone Marrow Transplant 2001; 28: 557–562.

    CAS  PubMed  Google Scholar 

  88. Grigg A, Kannan K, Schwarer AP, Spencer A, Szer J . Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-alpha for relapsed malignancy after allogeneic bone marrow transplantation. Intern Med J 2001; 31: 15–22.

    CAS  PubMed  Google Scholar 

  89. Singhal S, Powles R, Treleaven J, Mehta J . Sensitivity of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation to immunotherapy with interferon-alpha 2b. Bone Marrow Transplant 1997; 19: 1151–1153.

    CAS  PubMed  Google Scholar 

  90. Kishi K, Takahashi S, Gondo H, Shiobara S, Kanamaru A, Kato S et al. Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplant 1997; 19: 461–466.

    CAS  PubMed  Google Scholar 

  91. Mrsic M, Horowitz MM, Atkinson K, Biggs JC, Champlin RE, Ehninger G et al. Second HLA-identical sibling transplants for leukemia recurrence. Bone Marrow Transplant 1992; 9: 269–275.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Professor Charlie Craddock for a critical review of the manuscript and to Professor Grant Prentice and Dr Kim Orchard for helpful discussions.

Author information

Authors and Affiliations

  1. Section of Haemato-Oncology, Royal Marsden Hospital, Surrey, UK

    B E Shaw

  2. Anthony Nolan Research Institute, London, UK

    B E Shaw

  3. Department of Haematology, Nottingham University Hospitals, Nottingham, UK

    N H Russell

Authors
  1. B E Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N H Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B E Shaw.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shaw, B., Russell, N. Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant. Bone Marrow Transplant 41, 495–503 (2008). https://doi.org/10.1038/sj.bmt.1705888

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705888

Keywords

This article is cited by

Search

Advanced search

Quick links