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The Beneficial Effect of Chronic Graft-versus-Host Disease on the Clinical Outcome of Transplantation with Fludarabine/Busulfan-Based Reduced-Intensity Conditioning for Patients with De Novo Myelodysplastic Syndrome

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Abstract

Allogeneic hematopoietic stem cell transplantation following reduced-intensity stem cell transplantation (RIST) has enabled the treatment of older or medically infirm patients with myeloid malignancies; however, determining the value of RIST outcomes for myelodysplastic syndrome (MDS) is difficult because of the heterogeneity of the diseases included in most trials. To define the role of RIST in MDS, we performed RIST for 22 consecutive patients who had de novo MDS as classified by World Health Organization (WHO) criteria and who received an allograft with fludarabine/busulfan (Busulfex) or fludarabine/Busulfex/antithymocyte globulin (ATG) conditioning. Nineteen patients (86.4%) achieved engraftment. At a median follow-up of 18.9 months (range, 13.1–24.8 months), the estimated 2-year rates of overall survival, event-free survival (EFS), transplantation-related mortality, and relapse were 78.7%, 67.7%, 12.6%, and 22.5%, respectively. Acute graft-versus-host disease (GVHD) greater than grade II developed in 3 patients (15.8%). Chronic GVHD developed in 10 patients (55.6%), none of whom received ATG as a conditioning regimen. Variables influencing EFS were chronic GVHD, marrow blasts before transplantation, and the WHO criteria. The present study clarifies the benefits of the fludarabine/Busulfex-based conditioning regimen for de novo MDS diagnosed according to the WHO criteria and shows that chronic GVHD appears to have a beneficial effect on survival rates, which are strongly associated with graft-versus-tumor effects.

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References

  1. Jacobs A. Leukaemia Research Fund annual guest lecture 1990: genetics lesions in preleukaemia. Leukemia. 1991;5:277–282.

    PubMed  CAS  Google Scholar 

  2. Raza A, Meyer P, Dutt D, et al. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood. 2001;98:958–965.

    Article  PubMed  CAS  Google Scholar 

  3. Kurzrock R, Albitar M, Cortes JE, et al. Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J Clin Oncol. 2004;22:1287–1292.

    Article  PubMed  CAS  Google Scholar 

  4. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2002;20:2429–2440.

    Article  PubMed  CAS  Google Scholar 

  5. Sierra J, Perez WS, Rozman C, et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood. 2002;100:1997–2004.

    CAS  PubMed  Google Scholar 

  6. Kim YJ, Kim DW, Lee S, et al. Comparison of 2 preparative regi- mens for stem cell transplantation from HLA-matched sibling donors in patients with advanced myelodysplastic syndrome. Int J Hematol. 2005;82:66–71.

    Article  PubMed  Google Scholar 

  7. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997;89:4531–4536.

    PubMed  CAS  Google Scholar 

  8. Slavin S, Nagler A, Naparstek E, 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. 1998;91:756–763.

    PubMed  CAS  Google Scholar 

  9. Bornhäuser M, Thiede C, Schuler U, et al. Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraft- ment without antithymocyte globulin. Bone Marrow Transplant. 2000;26:119–125.

    Article  PubMed  Google Scholar 

  10. Mohty M, Bay JO, Faucher C, et al. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. Blood. 2003;102:470–476.

    Article  CAS  PubMed  Google Scholar 

  11. Bornhäuser 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.

    Article  CAS  PubMed  Google Scholar 

  12. Kroger N, Bornhäuser M, Ehninger G, et al, and the German Cooperative Transplant Study Group. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol. 2003;82:336–342.

    Article  PubMed  CAS  Google Scholar 

  13. Hamaki T, Kami M, Kim SW, et al. Reduced-intensity stem cell transplantation from an HLA-identical sibling donor in patients with myeloid malignancies. Bone Marrow Transplant. 2004;33:891–900.

    Article  PubMed  CAS  Google Scholar 

  14. Schetelig J, Bornhäuser M, Kiehl M, et al, for the Cooperative German Transplant Study Group. Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation: a retrospective analysis. Bone Marrow Transplant. 2004;33:483–490.

    Article  PubMed  CAS  Google Scholar 

  15. Kroger N, Schetelig J, Zabelina T, et al. A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome. Bone Marrow Transplant. 2001;28:643–647.

    Article  PubMed  CAS  Google Scholar 

  16. Parker JE, Shafi T, Pagliuca A, et al. Allogeneic stem cell transplantation in the myelodysplastic syndromes: interim results of outcome following reduced-intensity conditioning compared with standard preparative regimens. Br J Haematol. 2002;119:144–154.

    Article  PubMed  Google Scholar 

  17. Chan GW, Foss FM, Klein AK, Sprague K, Miller KB. Reduced-intensity transplantation for patients with myelodysplastic syndrome achieves durable remission with less graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9:753–759.

    Article  PubMed  Google Scholar 

  18. Ho AY, Pagliuca A, Kenyon M, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood. 2004;104:1616–1623.

    Article  PubMed  CAS  Google Scholar 

  19. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088.

    PubMed  CAS  Google Scholar 

  20. Kim HJ, Park CY, Park YH, et al. Successful allogeneic hematopoietic stem cell transplantation using triple agent immunosuppres- sion in severe aplastic anemia patients. Bone Marrow Transplant. 2003;31:79–86.

    Article  PubMed  CAS  Google Scholar 

  21. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL- A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. Cutler C, Giri S, Jeyapalan S, Paniagua D, Viswanathan A, Antin JH. Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol. 2001;19:3685–3691.

    Article  PubMed  CAS  Google Scholar 

  24. Gustafsson Jernberg A, Remberger M, Ringden O, Winiarski J. Graft-versus-leukaemia effect in children: chronic GVHD has a significant impact on relapse and survival. Bone Marrow Transplant. 2003;31:175–181.

    Article  Google Scholar 

  25. Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood. 2003;102:756–762.

    Article  PubMed  CAS  Google Scholar 

  26. Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol. 2003;21:1480–1484.

    Article  PubMed  Google Scholar 

  27. Baron F, Maris MB, Sandmaier BM, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005;23:1993–2003.

    Article  PubMed  Google Scholar 

  28. Nakai K, Mineishi S, Kami M, et al. Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution. Transplantation. 2003;75:2135–2143.

    Article  CAS  PubMed  Google Scholar 

  29. Bacigalupo A. Antithymocyte globulin for prevention of graft-versus-host disease. Curr Opin Hematol. 2005;12:457–462.

    Article  CAS  PubMed  Google Scholar 

  30. Mielcarek M, Storb R. Graft-vs-host disease after non-myeloabla-tive hematopoietic cell transplantation. Leuk Lymphoma. 2005;46:1251–1260.

    Article  CAS  PubMed  Google Scholar 

  31. Scott BL, Storer B, Loken M, Storb R, Appelbaum FR, Deeg HJ. Pretransplantation induction chemotherapy and posttransplanta- tion relapse in patients with advanced myelodysplastic syndrome. Biol Blood Marrow Transplant. 2005;11:65–73.

    Article  PubMed  Google Scholar 

  32. Martino R, Iacobelli S, Brand R, et al, for the Myelodysplastic Syndrome subcommittee of the Chronic Leukemia Working Party of the European Blood and Marrow Transplantation Group. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood. 2006;108:836–846.

    Article  CAS  PubMed  Google Scholar 

  33. Kebriaei P, Kline J, Stock W, et al. Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant. 2005;35:965–970.

    Article  CAS  PubMed  Google Scholar 

  34. Wong R, Giralt SA, Martin T, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood. 2003;102:3052–3059.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    Article  PubMed  CAS  Google Scholar 

  36. Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood. 2005;105:1810–1814.

    Article  PubMed  CAS  Google Scholar 

  37. Aoudjhane M, Labopin M, Gorin NC, et al, on behalf of the Acute Leukemia Working Party of EBMT. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia. 2005;19:2304–2312.

    Article  PubMed  CAS  Google Scholar 

  38. Crawley C, Lalancette M, Szydlo R, et al, for the Chronic Leukaemia Working Party of the EBMT. Outcomes for reduced- intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood. 2005;105:4532–4539.

    Article  CAS  PubMed  Google Scholar 

  39. Runde V, de Witte T, Arnold R, et al, on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Bone Marrow Transplant. 1998;21:255–261.

    Article  CAS  PubMed  Google Scholar 

  40. Cutler CS, Lee SJ, Greenberg P, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004;104:579–585.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Catholic Hematopoietic Stem Cell Transplantation Center, The Catholic University of Korea, #62 Yeouido-dong, Yeongdeungpo-ku, 150-713, Seoul, Korea

    Byung-Sik Cho, Yoo-Jin Kim, Seok-Goo Cho, Sung-Yong Kim, Ki-Seong Eom, Hee-Je Kim, Seok Lee, Chang-Ki Min, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min & Chun-Choo Kim

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  1. Byung-Sik Cho
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Correspondence to Seok-Goo Cho.

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Cho, BS., Kim, YJ., Cho, SG. et al. The Beneficial Effect of Chronic Graft-versus-Host Disease on the Clinical Outcome of Transplantation with Fludarabine/Busulfan-Based Reduced-Intensity Conditioning for Patients with De Novo Myelodysplastic Syndrome. Int J Hematol 85, 446–455 (2007). https://doi.org/10.1532/IJH97.A30616

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  • DOI: https://doi.org/10.1532/IJH97.A30616

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