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Unrelated-Donor Bone Marrow Transplantation with a Conditioning Regimen Including Fludarabine, Busulfan, and 4 Gy Total Body Irradiation

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Abstract

We investigated the feasibility of reduced-intensity conditioning with 4 Gy total body irradiation, fludarabine (30 mg/m2 for 6 days), and busulfan (4 mg/kg for 2 days) for bone marrow transplantation from a serologically HLA-matched unrelated donor. Seventeen adult patients (median age, 55 years; range, 27-67 years) with various hematologic malignancies (6 in remission, 11 not in remission) were treated. Successful engraftment was achieved in all patients at a median of day 18 (range, day 14-35) after transplantation, although subsequent secondary graft failure was observed in 2 patients. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV at day 100 was 48%. With a median follow-up of 286 days (range, 56-687 days), the rates of 1-year overall survival, 100-day nonrelapse mortality, and 1-year nonrelapse mortality were 41%, 14%, and 46%, respectively. Eleven patients died, and the causes of death were relapse (n = 4), pulmonary complications (n = 4), acute GVHD (n = 2), and sepsis (n = 1). The remaining 6 patients (at transplantation, 2 were in remission, and 4 were not in remission) are currently still in remission. These results suggest that this regimen reduces the risk of graft failure, but further studies are needed to ameliorate transplantation-related toxicities, primarily GVHD and/or pulmonary complications. cr 2007 The Japanese Society of Hematology

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References

  1. Kanda Y, Chiba S, Hirai H, et al. Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).Blood. 2003;102:1541–1547.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Khouri IF, Keating M, Korbling M, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.J Clin Oncol. 1998;16:2817–2824.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    CAS  PubMed  Google Scholar 

  5. Childs R, Clave E, Contentin N, et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses.Blood. 1999;94:3234–3241.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies.Blood. 2003;102:2021–2030.

    Article  PubMed  CAS  Google Scholar 

  9. Bornhauser M, Thiede C, Platzbecker U, et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients.Clin Cancer Res. 2001;7:2254–2262.

    PubMed  CAS  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. Nagler A, Aker M, Or R, et al. Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation.Exp Hematol. 2001;29:362–370.

    Article  PubMed  CAS  Google Scholar 

  12. Kroger N, Sayer HG, Schwerdtfeger R, et al. Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality.Blood. 2002;100:3919–3924.

    Article  PubMed  CAS  Google Scholar 

  13. Bornhauser M, Storer B, Slattery JT, et al. Conditioning with flu-darabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells.Blood. 2003;102:820–826.

    Article  PubMed  CAS  Google Scholar 

  14. Niederwieser D, Maris M, Shizuru JA, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclo-sporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases.Blood. 2003;101:1620–1629.

    Article  CAS  PubMed  Google Scholar 

  15. 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 

  16. Rodriguez R, Parker P, Nademanee A, et al. Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies.Bone Marrow Transplant. 2004;33:1123–1129.

    Article  PubMed  CAS  Google Scholar 

  17. Inamoto Y, Oba T, Miyamura K, et al. Stable engraftment after a conditioning regimen with fludarabine and melphalan for bone marrow transplantation from an unrelated donor.Int J Hematol. 2006;83:356–362.

    Article  PubMed  Google Scholar 

  18. Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation.Semin Hematol. 1991;28:250–259.

    PubMed  CAS  Google Scholar 

  19. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading.Bone Marrow Transplant. 1995;15:825–828.

    PubMed  CAS  Google Scholar 

  20. Deeg HJ, Amylon ID, Harris RE, et al. Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation.Biol Blood Marrow Transplant. 2001;7:208–215.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. Hale G, Jacobs P, Wood L, et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells.Bone Marrow Transplant. 2000;26:69–76.

    Article  PubMed  CAS  Google Scholar 

  23. Chakraverty R, Peggs K, Chopra R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen.Blood. s2002;99:1071–1078.

    Article  Google Scholar 

  24. 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 

  25. van Besien K, Artz A, Smith S, et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome.J Clin Oncol. 2005; 23: 5728–5738.

    Article  PubMed  CAS  Google Scholar 

  26. Lim ZY, Ho AY, Ingram W, et al. Outcomes of alemtuzumab-based reduced intensity conditioning stem cell transplantation using unrelated donors for myelodysplastic syndromes.Br J Haematol. 2006;135:201–209.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan

    Yasushi Onishi, Shin-ichiro Mori, Shigeru Kusumoto, Kyoko Sugimoto, Daigo Akahane, Yuriko Morita-Hoshi, Sung-Won Kim, Takahiro Fukuda, Yuji Heike, Ryuji Tanosaki, Kensei Tobinai & Yoichi Takaue

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  1. Yasushi Onishi
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  2. Shin-ichiro Mori
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  3. Shigeru Kusumoto
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  4. Kyoko Sugimoto
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  5. Daigo Akahane
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  6. Yuriko Morita-Hoshi
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  7. Sung-Won Kim
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  8. Takahiro Fukuda
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  9. Yuji Heike
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  10. Ryuji Tanosaki
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  11. Kensei Tobinai
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  12. Yoichi Takaue
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Correspondence to Yoichi Takaue.

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Onishi, Y., Mori, Si., Kusumoto, S. et al. Unrelated-Donor Bone Marrow Transplantation with a Conditioning Regimen Including Fludarabine, Busulfan, and 4 Gy Total Body Irradiation. Int J Hematol 85, 256–263 (2007). https://doi.org/10.1532/IJH97.06199

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  • DOI: https://doi.org/10.1532/IJH97.06199

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