Biology of Blood and Marrow Transplantation
Volume 15, Issue 11 , Pages 1376-1385 , November 2009

Sequential Intensified Conditioning and Tapering of Prophylactic Immunosuppressants for Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation for Refractory Leukemia

  • Qi-Fa Liu

      Affiliations

    • Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    • Corresponding Author InformationCorrespondence and reprint requests: Qi-Fa Liu, Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • ,
  • Zhi-Ping Fan

      Affiliations

    • Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • ,
  • Yu Zhang

      Affiliations

    • Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • ,
  • Zu-Jun Jiang

      Affiliations

    • Department of Hematology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China
  • ,
  • Chun-Yan Wang

      Affiliations

    • Centre of Oncology and Hematology, First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510230, China
  • ,
  • Dan Xu

      Affiliations

    • Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • ,
  • Jing Sun

      Affiliations

    • Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • ,
  • Yang Xiao

      Affiliations

    • Department of Hematology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China
  • ,
  • Huo Tan

      Affiliations

    • Centre of Oncology and Hematology, First Affiliated Hospital, Guangzhou Medical College, Guangzhou 510230, China

Received 12 May 2009 ,Accepted 26 June 2009.

References 

  1. Thomas MB, Koller C, Yang Y, et al. Comparison of fludarabine-containing salvage chemotherapy regimens for relapsed/refractory acute myelogenous leukemia. Leukemia. 2003;17:990–993
  2. Giebel S, Krawczyk-Kulis M, Adamczyk-Cioch M, et al. Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult acute lymphoblastic leukemia; a phase study by the Polish Adult Leukemia Group (PALG). Ann Hematol. 2006;85:717–722
  3. Mato AR, Morgans A, Luger SM. Novel strategies for relapsed and refractory acute myeloid leukemia. Curr Opin Hematol. 2008;15:108–114
  4. Biggs JC, Horowitz MM, Gale RP, et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood. 1992;80:1090–1093
  5. Fung HC, Stein A, Slovak M, et al. A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome. Biol Blood Marrow Transplant. 2003;9:766–771
  6. Oyekunle AA, Kroger N, Zabelina T, et al. Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up. Bone Marrow Transplant. 2006;37:45–50
  7. Schmid C, Schleuning M, Schwerdtfeger R, 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
  8. Clift RA, Buckner CD, Thomas ED, et al. The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation. Bone Marrow Transplant. 1987;2:243–258
  9. Sierra J, Storer B, Hansen JA, et al. Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA matching, and marrow cell dose. Blood. 1997;89:4226–4235
  10. Appelbaum FR, Clift RA, Buckner CD, et al. Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse. Blood. 1983;61:949–953
  11. Thomas ED, Sanders JE, Flournoy N, et al. Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up. Blood. 1983;62:1139–1141
  12. Ringden O, Labopin M, Tura S, et al. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 1996;93:637–645
  13. Aurer I, Gale RP. Are new conditioning regimens for transplants in acute myelogenous leukemia better?. Bone Marrow Transplant. 1991;7:255–261
  14. Mengarelli A, Iori A, Guglielmi C, et al. Standard versus alternative myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia. Haematologica. 2002;87:52–58
  15. Giralt S, Thall PF, Khouri I, et al. Melphalan and purine analog–containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood. 2001;97:631–637
  16. McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001;97:3390–3400
  17. Rezvani K, Lalancette M, Mackinnon S, et al. Non-myeloablative stem cell transplantation in AML, ALL and MDS: disappointing outcome for patients with advanced disease [abstract]. Blood. 2000;96(Suppl):2061
  18. Mineishi S, Longo WL, Atkinson ME, et al. Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity. Bone Marrow Transplant. 1999;23:1217–1222
  19. de Lima M, Anagnostopoulos A, Munsell M, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood. 2004;104:865–872
  20. Schmid C, Schleuning M, Ledderose G, et al. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23:5675–5687
  21. de Lima M, Bonamino M, Vasconcelos Z, 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
  22. Huang XJ, Wang Y, Liu DH, et al. Modified donor lymphocyte infusion (DLI) for the prophylaxis of leukemia relapse after hematopoietic stem cell transplantation in patients with advanced leukemia: feasibility and safety study. J Clin Immunol. 2008;28:390–397
  23. Odom LF, August CS, Githens JH, et al. Remission of relapsed leukaemia during a graft-versus-host reaction: a “graft-versus-leukaemia reaction” in man. Lancet. 1978;2:537–540
  24. Higano CS, Brixey M, Bryant EM, 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
  25. Elmaagacli AH, Beelen DW, Trenn G, et al. Induction of a graft-versus-leukemia reaction by cyclosporin A withdrawal as immunotherapy for leukemia relapsing after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1999;23:771–777
  26. Liu QF, Sun J, Xu D, et al. Effects of allogeneic hematopoietic stem cell transplantation with very–high-dose conditioning regimen for refractory leukemia. Di Yi Jun Yi Da Xue Xue Bao. 2004;24:1117–1119
  27. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17:3835–3849
  28. Bearman SI, Appelbaum FR, Buckner CD, et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol. 1988;6:1562–1568
  29. Sullivan KM. Graft-versus-host-disease. In:  Blume KG,  Forman SJ,  Appelbaum FR editor. Thomas' Hematopoietic Cell Transplantation. 3rd ed. Malden, MA: Blackwell; 2004;p. 635–664
  30. Mrozek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 2004;18:115–136
  31. Stockerl-Goldstein KE, Blume KG. Allogeneic haematopoietic cell transplantation for adult patients with acute myeloid leukemia. In:  Blume KG,  Forman SJ,  Appelbaum FR editor. Thomas' Hematopoietic Cell Transplantation. 3rd ed. Malden, MA: Blackwell; 2004;p. 1025–1039
  32. Mehta J, Powles R, Horton C, et al. Bone marrow transplantation for primary refractory acute leukaemia. Bone Marrow Transplant. 1994;14:415–418
  33. Ringden O, Labopin M, Bacigalupo A, et al. Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol. 2002;20:4655–4664
  34. Russell JA, Tran HT, Quinlan D, et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002;8:468–476
  35. Bornhauser M, Storer B, Slattery JT, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood. 2003;102:820–826
  36. de Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104:857–864
  37. Petersen FB, Appelbaum FR, Buckner CD, et al. Simultaneous infusion of high-dose cytosine arabinoside with cyclophosphamide followed by total body irradiation and marrow infusion for the treatment of patients with advanced hematological malignancy. Bone Marrow Transplant. 1988;3:619–624
  38. Trigg ME, Finlay JL, Bozdech M, et al. Fatal cardiac toxicity in bone marrow transplant patients receiving cytosine arabinoside, cyclophosphamide, and total body irradiation. Cancer. 1987;59:38–42
  39. Riddell S, Appelbaum FR, Buckner CD, et al. High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia. J Clin Oncol. 1988;6:576–582
  40. Moussalem M, Esperou BH, Devergie A, et al. Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission: factors predictive of survival, relapse and graft-versus-host disease. Bone Marrow Transplant. 1995;15:943–947
  41. Gordon BG, Warkentin PI, Strandjord SE, et al. Allogeneic bone marrow transplantation for children with acute leukemia: long-term follow-up of patients prepared with high-dose cytosine arabinoside and fractionated total body irradiation. Bone Marrow Transplant. 1997;20:5–10
  42. Helenglass G, Powles RL, McElwain TJ, et al. Melphalan and total body irradiation (TBI) versus cyclophosphamide and TBI as conditioning for allogeneic matched sibling bone marrow transplants for acute myeloblastic leukaemia in first remission. Bone Marrow Transplant. 1988;3:21–29
  43. Woods WG, Ramsay NK, Weisdorf DJ, et al. Bone marrow transplantation for acute lymphocytic leukemia utilizing total body irradiation followed by high doses of cytosine arabinoside: lack of superiority over cyclophosphamide-containing conditioning regimens. Bone Marrow Transplant. 1990;6:9–16
  44. Engelhard D, Elishoov H, Or R, et al. Cytosine arabinoside as a major risk factor for Streptococcus viridans septicemia following bone marrow transplantation: a 5-year prospective study. Bone Marrow Transplant. 1995;16:565–570
  45. Drobyski WR, Keever CA, Roth MS, et al. 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. 1993;82:2310–2318
  46. Porter DL, Roth MS, McGarigle C, et al. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med. 1994;330:100–106
  47. Michallet M, Thomas X, Vernant JP, et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced-stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant. 2000;26:1157–1163
  48. Terwey TH, Massenkeil G, Tamm I, et al. Allogeneic SCT in refractory or relapsed adult ALL is effective without prior reinduction chemotherapy. Bone Marrow Transplant. 2008;42:791–798
  49. Doney K, Hägglund H, Leisenring W, et al. Predictive factors for outcome of allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2003;9:472–481

 Financial disclosure: See Acknowledgments on page 1384.

PII: S1083-8791(09)00303-6

doi: 10.1016/j.bbmt.2009.06.017

Biology of Blood and Marrow Transplantation
Volume 15, Issue 11 , Pages 1376-1385 , November 2009