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Feasibility of Non-TBI Conditioning with Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation in Lymphoid Malignancy

  • Shin, Ho-Cheol (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Lee, Yoo-Jin (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Moon, Joon-Ho (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Lee, Soo-Jung (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Kang, Byung-Woog (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Chae, Yee-Soo (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Kim, Jong-Gwang (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Choi, Jun-Young (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Seo, Jong-Won (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Kim, Yu-Kyung (Department of Laboratory Medicine, Kyungpook National University Hospital) ;
  • Suh, Jang-Soo (Department of Laboratory Medicine, Kyungpook National University Hospital) ;
  • Sohn, Sang-Kyun (Department of Hematology/Oncology, Kyungpook National University Hospital)
  • 발행 : 2012.03.01

초록

Background/Aims: This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2). Methods: Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients. Eight and 13 patients were high risk disease in the BuCy2 and BuFlu groups, respectively. Results: The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2 groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively. Treatment-related mortality (TRM) was significantly lower in the BuFlu group (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the BuFlu regimen was identified as an independent favorable risk factor for TRM (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p = 0.034). Conclusions: Our BuFlu regimen would appear to be an acceptable conditioning option for lymphoid malignancies, including high-risk diseases. It was safely administered with a lower TRM rate than BuCy2 conditioning.

키워드

참고문헌

  1. 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. https://doi.org/10.1046/j.1365-2141.1996.d01-1681.x
  2. Litzow MR, Perez WS, Klein JP, et al. Comparison of outcome following allogeneic bone marrow transplantation with cyclophosphamide-total body irradiation versus busulphan-cyclophosphamide conditioning regimens for acute myelogenous leukaemia in first remission. Br J Haematol 2002;119:1115-1124. https://doi.org/10.1046/j.1365-2141.2002.03973.x
  3. Blaise D, Maraninchi D, Archimbaud E, et al. Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse. Blood 1992;79:2578-2582.
  4. Devergie A, Blaise D, Attal M, et al. Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-cytoxan versus cytoxantotal body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graft (SFGM). Blood 1995;85:2263-2268.
  5. Socie G, Clift RA, Blaise D, et al. Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies. Blood 2001;98:3569-3574. https://doi.org/10.1182/blood.V98.13.3569
  6. Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant 2003;32:543-548. https://doi.org/10.1038/sj.bmt.1704198
  7. Davies SM, Ramsay NK, Klein JP, et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol 2000;18:340-347. https://doi.org/10.1200/JCO.2000.18.2.340
  8. DeLeve LD. Cellular target of cyclophosphamide toxicity in the murine liver: role of glutathione and site of metabolic activation. Hepatology 1996;24:830-837. https://doi.org/10.1002/hep.510240414
  9. Shulman HM, Luk K, Deeg HJ, Shuman WB, Storb R. Induction of hepatic veno-occlusive disease in dogs. Am J Pathol 1987;126:114-125.
  10. Terenzi A, Aristei C, Aversa F, et al. Efficacy of fludarabine as an immunosuppressor for bone marrow transplantation conditioning: preliminary results. Transplant Proc 1996;28:3101.
  11. Chun HG, Leyland-Jones B, Cheson BD. Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. J Clin Oncol 1991;9:175-188. https://doi.org/10.1200/JCO.1991.9.1.175
  12. Chae YS, Sohn SK, Kim JG, et al. New myeloablative conditioning regimen with fludarabine and busulfan for allogeneic stem cell transplantation: comparison with BuCy2. Bone Marrow Transplant 2007;40:541-547. https://doi.org/10.1038/sj.bmt.1705770
  13. Iravani M, Evazi MR, Mousavi SA, et al. Fludarabine and busulfan as a myeloablative conditioning regimen for allogeneic stem cell transplantation in high- and standard-risk leukemic patients. Bone Marrow Transplant 2007;40:105-110. https://doi.org/10.1038/sj.bmt.1705685
  14. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995;15:825-828.
  15. Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980;69:204-217. https://doi.org/10.1016/0002-9343(80)90380-0
  16. Kim HJ, Chung IJ, Lee JJ, et al. A case of chronic graft-versus-host-disease following allogeneic peripheral blood stem cell rescue for poor graft function after bone marrow transplantation. Korean J Intern Med 1998;13:60-63. https://doi.org/10.3904/kjim.1998.13.1.60
  17. Bacigalupo A, Lamparelli T, Bruzzi P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood 2001;98:2942-2947. https://doi.org/10.1182/blood.V98.10.2942
  18. Giaccone L, Martin P, Carpenter P, et al. Safety and potential efficacy of low-dose methotrexate for treatment of chronic graftversus- host disease. Bone Marrow Transplant 2005;36:337-341. https://doi.org/10.1038/sj.bmt.1705022
  19. Copelan EA, Biggs JC, Avalos BR, et al. Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia. J Clin Oncol 1992;10:237-242. https://doi.org/10.1200/JCO.1992.10.2.237
  20. Granados E, de La Camara R, Madero L, et al. Hematopoietic cell transplantation in acute lymphoblastic leukemia: better long term event-free survival with conditioning regimens containing total body irradiation. Haematologica 2000;85:1060-1067.
  21. Slattery JT, Clift RA, Buckner CD, et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood 1997;89:3055-3060.
  22. Ljungman P, Hassan M, Bekassy AN, Ringden O, Oberg G. High busulfan concentrations are associated with increased transplant-related mortality in allogeneic bone marrow transplant patients. Bone Marrow Transplant 1997;20:909-913. https://doi.org/10.1038/sj.bmt.1700994
  23. Grochow LB, Krivit W, Whitley CB, Blazar B. Busulfan disposition in children. Blood 1990;75:1723-1727.
  24. Schuler U, Schroer S, Kuhnle A, et al. Busulfan pharmacokinetics in bone marrow transplant patients: is drug monitoring warranted? Bone Marrow Transplant 1994;14:759-765.
  25. Vassal G, Gouyette A, Hartmann O, Pico JL, Lemerle J. Pharmacokinetics of high-dose busulfan in children. Cancer Chemother Pharmacol 1989;24:386-390.
  26. Kashyap A, Wingard J, Cagnoni P, et al. Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality. Biol Blood Marrow Transplant 2002;8:493-500. https://doi.org/10.1053/bbmt.2002.v8.pm12374454
  27. Imamura M, Tanaka J. Graft-versus-leukemia effect of nonmyeloablative stem cell transplantation. Korean J Intern Med 2009;24:287-298. https://doi.org/10.3904/kjim.2009.24.4.287
  28. Shah AJ, Lenarsky C, Kapoor N, et al. Busulfan and cyclophosphamide as a conditioning regimen for pediatric acute lymphoblastic leukemia patients undergoing bone marrow transplantation. J Pediatr Hematol Oncol 2004;26:91-97. https://doi.org/10.1097/00043426-200402000-00004
  29. Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/ maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008;111:1827-1833. https://doi.org/10.1182/blood-2007-10-116582

피인용 문헌

  1. Busulfan fludarabine vs busulfan cyclophosphamide as a preparative regimen before allogeneic hematopoietic cell transplantation: systematic review and meta-analysis vol.51, pp.2, 2016, https://doi.org/10.1038/bmt.2015.238
  2. 한약복합추출물(NI-01)의 항염증 및 소양감 억제 효과 vol.34, pp.6, 2012, https://doi.org/10.15188/kjopp.2020.12.34.6.341