Reduced-Intensity and Nonmyeloablative Conditioning Regimens

  • Francine Foss
  • Koen van Besien
Part of the Cancer Treatment and Research book series (CTAR, volume 144)

Alternative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation

Preparative regimens for allogeneic hematopoietic stem cell transplantation (HSCT) must address two immunologic barriers to establish successful hematopoietic engraftment: the host-versus-graft effect (HvG) and the graft-versus-host (GvH) effect. High-dose chemotherapy combined with sublethal doses of radiation therapy has been used to immune suppress the host sufficiently to prevent rejection of donor cells. Although effective in most patients, the original myeloablative regimens based on high dose TBI or busulfan are toxic to non-hematopoietic tissues and are associated with high transplant-associated morbidity and mortality, limiting the potential of this curative treatment to younger patients without underlying end organ dysfunction. Further, conventional ablative regimens require long-term immunosuppression to control GvHD, with resulting immune compromise and toxicity related to these agents.


Conditioning Regimen Total Body Irradiation Acute GvHD Allogeneic Hematopoietic Stem Cell Transplantation Chronic GvHD 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Storb RF, Champlin R, Riddell SR, et al. Non-myeloablative transplants for malignant disease. Hematology Am Soc Hematol Educ Program. 2001:375–91.Google Scholar
  2. 2.
    Diaconescu R, Flowers CR, Storer B, et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004;104:1550–8.PubMedGoogle Scholar
  3. 3.
    Chien JW, Maris MB, Sandmaier BM, et al. Comparison of lung function after myeloablative and 2 Gy of total body irradiation-based regimens for hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11:288–96.PubMedGoogle Scholar
  4. 4.
    Mielcarek M, Storer BE, Sandmaier BM, et al. Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors. Biol Blood Marrow Transplant. 2007;13:1499–507.PubMedGoogle Scholar
  5. 5.
    Khouri I, 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;16:2817–24.PubMedGoogle Scholar
  6. 6.
    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;89:4531–6.PubMedGoogle Scholar
  7. 7.
    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;91:756–63.PubMedGoogle Scholar
  8. 8.
    Sykes M, Preffer F, McAfee S, et al. Mixed lymphohaematopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone marrow transplantation. Lancet 1999;353:1755–9.PubMedGoogle Scholar
  9. 9.
    Daly A, McAfee S, Dey B, et al. Nonmyeloablative bone marrow transplantation: infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transplant. 2003;9:373–82.PubMedGoogle Scholar
  10. 10.
    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;97:3390–400.PubMedGoogle Scholar
  11. 11.
    Baron F, Baker JE, Storb R, et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004;104:2254–62.PubMedGoogle Scholar
  12. 12.
    Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003;102:756–62.PubMedGoogle Scholar
  13. 13.
    Hogan WJ, Maris M, Storer B, et al. Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients. Blood 2004;103:78–84.PubMedGoogle Scholar
  14. 14.
    Sorror ML, Maris MB, Storer B, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004;104:961–8.PubMedGoogle Scholar
  15. 15.
    Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000;343:750–8.PubMedGoogle Scholar
  16. 16.
    Schetelig J, Bornhauser M, Kiehl M, et al. Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation—a retrospective analysis. Bone Marrow Transplant. 2004;33:483–90.PubMedGoogle Scholar
  17. 17.
    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;21:1480–4.PubMedGoogle Scholar
  18. 18.
    Kottaridis PD, Milligan DW, Chopra R, et al. In vivo CAMPATH-1H prevents GvHD following nonmyeloablative stem-cell transplantation. Cytotherapy 2001;3:197–201.PubMedGoogle Scholar
  19. 19.
    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 2002;99:1071–8.PubMedGoogle Scholar
  20. 20.
    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;23:5728–38.PubMedGoogle Scholar
  21. 21.
    Morris E, Thomson K, Craddock C, et al. Outcome following Alemtuzumab (CAMPATH-1H)-containing reduced intensity allogeneic transplant regimen for relapsed and refractory non-Hodgkin’s lymphoma (NHL). Blood 2004;104:3865–71.PubMedGoogle Scholar
  22. 22.
    Novitzky N, Thomas V, du TC. Prevention of graft vs. host disease with alemtuzumab ”in the bag” decreases early toxicity of stem cell transplantation and in multiple myeloma is associated with improved long-term outcome. Cytotherapy 2008;10:45–53.PubMedGoogle Scholar
  23. 23.
    Novitzky N, Thomas V. Allogeneic stem cell transplantation with T cell-depleted grafts for lymphoproliferative malignancies. Biol Blood Marrow Transplant. 2007;13:107–15.PubMedGoogle Scholar
  24. 24.
    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.PubMedGoogle Scholar
  25. 25.
    Kline J, Pollyea DA, Stock W, et al. Pre-transplant ganciclovir and post transplant high-dose valacyclovir reduce CMV infections after alemtuzumab-based conditioning. Bone Marrow Transplant. 2006;37:307–10.PubMedGoogle Scholar
  26. 26.
    Chakrabarti S, Mackinnon S, Chopra R, et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 2002;99:4357–63.PubMedGoogle Scholar
  27. 27.
    Avivi I, Chakrabarti S, Milligan DW, et al. Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab. Biol Blood Marrow Transplant. 2004;10:186–94.PubMedGoogle Scholar
  28. 28.
    van Besien K, de Lima M, Artz A, et al. Alemtuzumab reduces chronic graft versus host disease (cGVHD) and treatment related mortality (TRM) after reduced intensity conditioning for AML and MDS. Blood (ASH Annual Meeting Abstracts). 2007;110:1076.Google Scholar
  29. 29.
    Shlomchik WD, Couzens MS, Tang CB, et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 1999;285:412–5.PubMedGoogle Scholar
  30. 30.
    Zhang PL, Malek SK, Prichard JW, et al. Monocyte-mediated acute renal rejection after combined treatment with preoperative Campath-1H (alemtuzumab) and postoperative immunosuppression. Ann Clin Lab Sci. 2004;34:209–13.PubMedGoogle Scholar
  31. 31.
    Trzonkowski P, Zilvetti M, Friend P, Wood KJ. Recipient memory-like lymphocytes remain unresponsive to graft antigens after CAMPATH-1H induction with reduced maintenance immunosuppression. Transplantation 2006;82:1342–51.PubMedGoogle Scholar
  32. 32.
    Simpson D. T-cell depleting antibodies: new hope for induction of allograft tolerance in bone marrow transplantation? BioDrugs 2003;17:147–54.PubMedGoogle Scholar
  33. 33.
    Ratzinger G, Reagan JL, Heller G, Busam KJ, Young JW. Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation. Blood 2003;101:1422–9.PubMedGoogle Scholar
  34. 34.
    Orsini E, Pasquale A, Maggio R, et al. Phenotypic and functional characterization of monocyte-derived dendritic cells in chronic lymphocytic leukaemia patients: influence of neoplastic CD19 cells in vivo and in vitro. Br J Haematol. 2004;125:720–8.PubMedGoogle Scholar
  35. 35.
    Morse MA, Mosca PJ, Clay TM, Lyerly HK. Dendritic cell maturation in active immunotherapy strategies. Expert Opin Biol Ther. 2002;2:35–43.PubMedGoogle Scholar
  36. 36.
    Kirsch BM, Haidinger M, Zeyda M, et al. Alemtuzumab (Campath-1H) induction therapy and dendritic cells: impact on peripheral dendritic cell repertoire in renal allograft recipients. Transpl Immunol. 2006;16:254–7.PubMedGoogle Scholar
  37. 37.
    Jordan MB, McClain KL, Yan X, Hicks J, Jaffe R. Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis. Pediatr Blood Cancer. 2005;44:251–4.PubMedGoogle Scholar
  38. 38.
    Collin MP, Munster D, Clark G, et al. In vitro depletion of tissue-derived dendritic cells by CMRF-44 antibody and alemtuzumab: implications for the control of graft-versus-host disease. Transplantation 2005;79:722–5.PubMedGoogle Scholar
  39. 39.
    Buggins AG, Mufti GJ, Salisbury J, et al. Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab. Blood 2002;100:1715–20.PubMedGoogle Scholar
  40. 40.
    Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004;26:473–503.PubMedGoogle Scholar
  41. 41.
    Auffermann-Gretzinger S, Eger L, Schetelig J, et al. Alemtuzumab depletes dendritic cells more effectively in blood than in skin: a pilot study in patients with chronic lymphocytic leukemia. Transplantation 2007;83:1268–72.PubMedGoogle Scholar
  42. 42.
    Auffermann-Gretzinger S, Eger L, Bornhauser M, et al. Fast appearance of donor dendritic cells in human skin: dynamics of skin and blood dendritic cells after allogeneic hematopoietic cell transplantation. Transplantation 2006;81:866–73.PubMedGoogle Scholar
  43. 43.
    Gorgun G, Miller KB, Foss FM. Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. Blood 2002;100:941–7.PubMedGoogle Scholar
  44. 44.
    Spisek R, Gasova Z, Bartunkova J. Maturation state of dendritic cells during the extracorporeal photopheresis and its relevance for the treatment of chronic graft-versus-host disease. Transfusion 2006;46:55–65.PubMedGoogle Scholar
  45. 45.
    Lamioni A, Parisi F, Isacchi G, et al. The immunological effects of extracorporeal photopheresis unraveled: induction of tolerogenic dendritic cells in vitro and regulatory T cells in vivo. Transplantation 2005;79:846–50.PubMedGoogle Scholar
  46. 46.
    Foss FM, Gorgun G, Miller KB. Extracorporeal photopheresis in chronic graft-versus-host disease. Bone Marrow Transplant. 2002;29:719–25.PubMedGoogle Scholar
  47. 47.
    Fimiani M, Di RM, Rubegni P. Mechanism of action of extracorporeal photochemotherapy in chronic graft-versus-host disease. Br J Dermatol. 2004;150:1055–60.PubMedGoogle Scholar
  48. 48.
    Di Renzo M, Sbano P, De Aloe G, et al. Extracorporeal photopheresis affects co-stimulatory molecule expression and interleukin-10 production by dendritic cells in graft-versus-host disease patients. Clin Exp Immunol. 2008;151:407–13.PubMedGoogle Scholar
  49. 49.
    Miller KB, Roberts TF, Chan G, et al. A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease. Bone Marrow Transplant. 2004;33:881–9.PubMedGoogle Scholar
  50. 50.
    Crawley C, Iacobelli S, Bjorkstrand B, et al. Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007;109:3588–94.PubMedGoogle Scholar
  51. 51.
    Hari P, Carreras J, Zhang MJ, et al. Allogeneic transplants in follicular lymphoma: higher risk of disease progression after reduced-intensity compared to myeloablative conditioning. Biol Blood Marrow Transplant. 2008;14:236–45.PubMedGoogle Scholar
  52. 52.
    Hansen JA, Gooley TA, Martin PJ, et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998;338:962–8.PubMedGoogle Scholar
  53. 53.
    Giralt SA, Kantarjian HM, Talpaz M, et al. Effect of prior interferon alfa therapy on the outcome of allogeneic bone marrow transplantation for chronic myelogenous leukemia. J Clin Oncol. 1993;11:1055–61.PubMedGoogle Scholar
  54. 54.
    Kebriaei P, Detry MA, Giralt S, et al. Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia. Blood 2007;110:3456–62.PubMedGoogle Scholar
  55. 55.
    Kerbauy FR, Storb R, Hegenbart U, et al. Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML. Leukemia 2005;19:990–7.PubMedGoogle Scholar
  56. 56.
    Or R, Shapira MY, Resnick I, et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood 2003;101:441–5.PubMedGoogle Scholar
  57. 57.
    Das M, Saikia TK, Advani SH, Parikh PM, Tawde S. Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia. Bone Marrow Transplant. 2003;32:125–9.PubMedGoogle Scholar
  58. 58.
    Sloand E, Childs RW, Solomon S, et al. The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia. Bone Marrow Transplant. 2003;32:897–901.PubMedGoogle Scholar
  59. 59.
    Crawley C, Szydlo R, Lalancette M, et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood 2005;106:2969–76.PubMedGoogle Scholar
  60. 60.
    Weisser M, Schleuning M, Ledderose G, et al. Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant. 2004;34:1083–8.PubMedGoogle Scholar
  61. 61.
    Oehler VG, Gooley T, Snyder DS, et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood 2007;109:1782–9.PubMedGoogle Scholar
  62. 62.
    Anderlini P, Sheth S, Hicks K, et al. Re: imatinib mesylate administration in the first 100 days after stem cell transplantation. Biol Blood Marrow Transplant. 2004;10:883–4.PubMedGoogle Scholar
  63. 63.
    Olavarria E, Siddique S, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood 2007;110:4614–7.PubMedGoogle Scholar
  64. 64.
    Devine SM, Hoffman R, Verma A, et al. Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia. Blood 2002;99:2255–8.PubMedGoogle Scholar
  65. 65.
    Rondelli D, Barosi G, Bacigalupo A, et al. Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia. Blood 2005;105:4115–9.PubMedGoogle Scholar
  66. 66.
    Deeg HJ, Gooley TA, Flowers ME, et al. Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Blood 2003;102:3912–8.PubMedGoogle Scholar
  67. 67.
    Laport GG, Sandmaier BM, Storer BE, et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant. 2008;14:246–55.PubMedGoogle Scholar
  68. 68.
    Koh LP, Chen CS, Tai BC, et al. Impact of postgrafting immunosuppressive regimens on nonrelapse mortality and survival after nonmyeloablative allogeneic hematopoietic stem cell transplant using the fludarabine and low-dose total-body irradiation 200-cGy. Biol Blood Marrow Transplant. 2007;13:790–805.PubMedGoogle Scholar
  69. 69.
    Oran B, Giralt S, Saliba R, et al. Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan. Biol Blood Marrow Transplant. 2007;13:454–62.PubMedGoogle Scholar
  70. 70.
    de Lima M, Anagnostopoulos A, Munsell M, et al. Non-Ablative 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;104:865–72.PubMedGoogle Scholar
  71. 71.
    Kroger N, Bornhauser M, Ehninger G, et al. 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;82:336–42.PubMedGoogle Scholar
  72. 72.
    Shimoni A, Hardan I, Shem-Tov N, et al. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia 2006;20:322–8.PubMedGoogle Scholar
  73. 73.
    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;23:5728–38.PubMedGoogle Scholar
  74. 74.
    Tauro S, Craddock C, Peggs K, et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol. 2005;23:9387–93.PubMedGoogle Scholar
  75. 75.
    Maruyama D, Fukuda T, Kato R, et al. Comparable antileukemia/lymphoma effects in nonremission patients undergoing allogeneic hematopoietic cell transplantation with a conventional cytoreductive or reduced-intensity regimen. Biol Blood Marrow Transplant. 2007;13:932–41.PubMedGoogle Scholar
  76. 76.
    Girgis M, Hallemeier C, Blum W, et al. Chimerism and clinical outcomes of 110 recipients of unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide. Blood 2005;105:3035–41.PubMedGoogle Scholar
  77. 77.
    Hallemeier C, Girgis M, Blum W, et al. Outcomes of adults with acute myelogenous leukemia in remission given 550 cGy of single-exposure total body irradiation, cyclophosphamide, and unrelated donor bone marrow transplants. Biol Blood Marrow Transplant. 2004;10:310–9.PubMedGoogle Scholar
  78. 78.
    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;108:1092–9.PubMedGoogle Scholar
  79. 79.
    Blaise DP, Michel Boiron J, Faucher C, et al. Reduced intensity conditioning prior to allogeneic stem cell transplantation for patients with acute myeloblastic leukemia as a first-line treatment. Cancer 2005;104:1931–8.PubMedGoogle Scholar
  80. 80.
    Mutis T, Goulmy E. Hematopoietic system-specific antigens as targets for cellular immunotherapy of hematological malignancies. Semin Hematol. 2002;39:23–31.PubMedGoogle Scholar
  81. 81.
    Molldrem JJ. Vaccination for leukemia. Biol Blood Marrow Transplant. 2006;12:13–8.PubMedGoogle Scholar
  82. 82.
    de Lima M, Padua L, Giralt S, et al. A dose and schedule finding study of maintenance therapy with low-dose 5-azacitidine (AZA) after allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk AML or MDS. Blood (ASH Annual Meeting Abstracts). 2007;110:3012.Google Scholar
  83. 83.
    de Lima M, Champlin RE, Thall PF, et al. Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome. Leukemia 2008;22:258–64.PubMedGoogle Scholar
  84. 84.
    Casper J, Knauf W, Kiefer T, et al. Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation. Blood 2004;103:725–31.PubMedGoogle Scholar
  85. 85.
    van Besien KW, Khouri IF, Giralt SA, et al. Allogeneic bone marrow transplantation for refractory and recurrent low grade lymphoma—the case for aggressive management. J Clin Oncol. 1995;13:1096–102.PubMedGoogle Scholar
  86. 86.
    van Besien K, Keralavarma B, Devine S, Stock W. Allogeneic and autologous transplantation for chronic lymphocytic leukemia. Leukemia 2001;15:1317–25.PubMedGoogle Scholar
  87. 87.
    van Besien K, Loberiza FR, Bajorunaite R, et al. Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 2003;102:3521–9.PubMedGoogle Scholar
  88. 88.
    Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol. 2004;32:28–35.PubMedGoogle Scholar
  89. 89.
    Khouri IF, Saliba RM, Admirand J, et al. Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. Br J Haematol. 2007;137:355–63.PubMedGoogle Scholar
  90. 90.
    Sorror ML, Maris MB, Sandmaier BM, et al. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol. 2005;23:3819–29.PubMedGoogle Scholar
  91. 91.
    Rezvani AR, Storer B, Maris M, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26:211–7.PubMedGoogle Scholar
  92. 92.
    Khouri IF, Saliba RM, Giralt SA, et al. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 2001;98:3595–9.PubMedGoogle Scholar
  93. 93.
    Delgado J, Thomson K, Russell N, et al. Results of alemtuzumab-based reduced-intensity allogeneic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study. Blood 2006;107:1724–30.PubMedGoogle Scholar
  94. 94.
    Sorror ML, Storer BE, Maloney DG, et al. Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood 2008;111:446–52.PubMedGoogle Scholar
  95. 95.
    Kahl C, Storer BE, Sandmaier BM, et al. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2007;110:2744–8.PubMedGoogle Scholar
  96. 96.
    Faulkner RD, Craddock C, Byrne JL, et al. BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood 2004;103:428–34.PubMedGoogle Scholar
  97. 97.
    Robinson SP, Goldstone AH, Mackinnon S, et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 2002;100:4310–6.PubMedGoogle Scholar
  98. 98.
    Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol. 2003;21:4407–12.PubMedGoogle Scholar
  99. 99.
    Maris MB, Sandmaier BM, Storer BE, et al. Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 2004;104:3535–42.PubMedGoogle Scholar
  100. 100.
    Gajewski JL, Phillips GL, Sobocinski KA, et al. Bone marrow transplants from HLA-identical siblings in advanced Hodgkin’s disease. J Clin Oncol. 1996;14:572–8.PubMedGoogle Scholar
  101. 101.
    Anderlini P, Saliba R, Acholonu S, et al. Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s disease: low transplant-related mortality and impact of intensity of conditioning regimen. Bone Marrow Transplant. 2005;35:943–51.PubMedGoogle Scholar
  102. 102.
    Peggs KS, Hunter A, Chopra R, et al. Clinical evidence of a graft-versus-Hodgkin’s-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet 2005;365:1934–41.PubMedGoogle Scholar
  103. 103.
    Thomson KJ, Peggs KS, Smith P, et al. Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin’s lymphoma following autologous stem cell transplantation. Bone Marrow Transplant. 2008 May; 41(9):765–70. Epub 2008 Jan 14.Google Scholar
  104. 104.
    Sureda A, Robinson S, Canals C, et al. Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26:455–62.PubMedGoogle Scholar
  105. 105.
    Devetten MP, Hari P, Carerras J, et al. Unrelated donor nonmyeloablative/reduced intensity (NST/RIC) hematopoietic stem cell transplantation (HCT) for patients with relapsed and refractory Hodgkin’s lymphoma (HL). Blood (ASH Annual Meeting Abstracts). 2006;108:601.Google Scholar
  106. 106.
    Pant S, Copelan EA. Hematopoietic stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2007;13:877–85.PubMedGoogle Scholar
  107. 107.
    Bensinger WI. The current status of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma. Leukemia 2006;20:1683–9.PubMedGoogle Scholar
  108. 108.
    Maloney DG, Molina AJ, Sahebi F, et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003;102:3447–54.PubMedGoogle Scholar
  109. 109.
    Kroger N, Schwerdtfeger R, Kiehl M, et al. Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma. Blood 2002;100:755–60.PubMedGoogle Scholar
  110. 110.
    Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356:1110–20.PubMedGoogle Scholar
  111. 111.
    Garban F, Attal M, Michallet M, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood 2006;107:3474–80.PubMedGoogle Scholar
  112. 112.
    van Besien K, Bartholomew A, Stock W, et al. Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. Bone Marrow Transplant. 2000;26:445–9.PubMedGoogle Scholar
  113. 113.
    Horwitz ME, Spasojevic I, Morris A, et al. Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics. Biol Blood Marrow Transplant. 2007;13:1422–6.PubMedGoogle Scholar
  114. 114.
    Walters MC, Patience M, Leisenring W, et al. Barriers to bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant. 1996;2:100–4.PubMedGoogle Scholar
  115. 115.
    Lucarelli G, Gaziev J. Advances in the allogeneic transplantation for thalassemia. Blood Rev. 2008;22:53–63.PubMedGoogle Scholar
  116. 116.
    Martino R, Valcarcel D, Brunet S, Sureda A, Sierra J. Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission. Bone Marrow Transplant. 2008;41:33–8.PubMedGoogle Scholar
  117. 117.
    van Besien K, Artz A, Stock W. Unrelated donor transplantation over the age of 55. Are we merely getting (b)older? Leukemia. 2005;19:31–3.PubMedGoogle Scholar
  118. 118.
    Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005;106:2912–9.PubMedGoogle Scholar
  119. 119.
    Sorror ML, Giralt S, Sandmaier BM, et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 2007;110:4606–13.PubMedGoogle Scholar
  120. 120.
    Sorror M, Storer B, Sandmaier BM, et al. Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 2008 May 1;112(9):1992–2001.Google Scholar
  121. 121.
    Artz A, Pollyea D, Kocherginsky M, et al. Performance status and comorbidity predict transplant related mortality after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2006 Sep;12(9):954–64.Google Scholar
  122. 122.
    Armand P, Kim HT, Cutler CS, et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007;109:4586–8.PubMedGoogle Scholar
  123. 123.
    Dinner SN, Artz A, Kocherginsky M, et al. Biomarkers to predict outcome after allogeneic hematopoietic cell transplant (HCT). Blood (ASH Annual Meeting Abstracts). 2007;110:1100.Google Scholar
  124. 124.
    Giralt S, Saliba RM, Mendoza F, et al. Pre transplant values of C reactive protein (CRP) and brain natriuretic peptide (BNP) as predictors of transplant outcomes in patients with acute myelogenous leukemia or myelodysplastic syndromes (AML/MDS) undergoing allogeneic stem cell transplantation (AlloSCT). Blood (ASH Annual Meeting Abstracts). 2007;110:1984.Google Scholar
  125. 125.
    Sandmaier BM, Mackinnon S, Childs RW. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. Biol Blood Marrow Transplant. 2007;13:87–97.PubMedGoogle Scholar
  126. 126.
    Nieto Y, Patton N, Hawkins T, et al. Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation. Biol Blood Marrow Transplant. 2006;12:217–25.PubMedGoogle Scholar
  127. 127.
    Stelljes M, Bornhauser M, Kroger M, et al. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood 2005;106:3314–21.PubMedGoogle Scholar
  128. 128.
    Dasgupta RK, Rule S, Johnson P, et al. Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect. Bone Marrow Transplant. 2006;37:455–61.PubMedGoogle Scholar
  129. 129.
    Shaw BE, Russell NH, Devereux S, et al. The impact of donor factors on primary non-engraftment in recipients of reduced intensity conditioned transplants from unrelated donors. Haematologica 2005;90:1562–9.PubMedGoogle Scholar
  130. 130.
    Spitzer TR, McAfee S, Sackstein R, et al. Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol Blood Marrow Transplant. 2000;6:309–20.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Medical Oncology and Bone Marrow Transplantation, Yale University School of MedicineNew HavenUSA

Personalised recommendations