Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Reduced-intensity conditioned allogeneic SCT in adults with AML

Subjects

Abstract

AML is currently the most common indication for reduced-intensity conditioned (RIC) allo-SCT. Reduced-intensity regimens allow a potent GVL response to occur with minimized treatment-related toxicity in patients of older age or with comorbidities that preclude the use of myeloablative conditioning. Whether RIC SCT is appropriate for younger and more standard risk patients is not well defined and the field is changing rapidly; a prospective randomized trial of myeloablative vs RIC (BMT-CTN 0901) was recently closed when early results indicated better outcomes for myeloablative regimens. However, detailed results are not available, and all patients in that study were eligible for myeloablative conditioning. RIC transplants will likely remain the standard of care as many patients with AML are not eligible for myeloablative conditioning. Recent publication of mature results from retrospective and prospective cohorts provide contemporary efficacy and toxicity data for these attenuated regimens. In addition, recent studies explore the use of alternative donors, introduce regimens that attempt to reduce toxicity without reducing intensity, and identify predictive factors that pave the way to personalized approaches. These studies paint a picture of the future of RIC transplants. Here we review the current status of RIC allogeneic SCT in AML.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068–1073.

    CAS  PubMed  Google Scholar 

  2. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  3. Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990; 76: 2462–2465.

    CAS  PubMed  Google Scholar 

  4. Porter DL, Roth MS, McGarigle C, Ferrara JL, Antin JH . Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med 1994; 330: 100–106.

    CAS  PubMed  Google Scholar 

  5. Quesenberry PJ, Ramshaw H, Crittenden RB, Stewart FM, Rao S, Peters S et al. Engraftment of normal murine marrow into nonmyeloablated host mice. Blood Cells 1994; 20: 348–350.

    CAS  PubMed  Google Scholar 

  6. Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.

    CAS  PubMed  Google Scholar 

  7. Porter DL, Connors JM, Van Deerlin VM, Duffy KM, McGarigle C, Saidman SL et al. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol 1999; 17: 1234.

    CAS  PubMed  Google Scholar 

  8. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG 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.

    CAS  PubMed  Google Scholar 

  9. Feinstein L, Sandmaier B, Maloney D, McSweeney PA, Maris M, Flowers C et al. Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect. Ann N Y Acad Sci 2001; 938: 328–337 discussion 337–329.

    CAS  PubMed  Google Scholar 

  10. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P 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.

    CAS  PubMed  Google Scholar 

  11. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G 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 

  12. Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S 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.

    CAS  PubMed  Google Scholar 

  13. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009; 15: 1628–1633.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2009; 15: 367–369.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Alyea EP, Kim HT, Ho V, Cutler C, Gribben J, DeAngelo DJ 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.

    CAS  PubMed  Google Scholar 

  16. Chen YB, Aldridge J, Kim HT, Ballen KK, Cutler C, Kao G et al. Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts. Biol Blood Marrow Transplant 2012; 18: 805–812.

    PubMed  Google Scholar 

  17. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C 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.

    CAS  PubMed  Google Scholar 

  18. Valcarcel D, Martino R, Caballero D, Martin J, Ferra C, Nieto JB et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol 2008; 26: 577–584.

    CAS  PubMed  Google Scholar 

  19. Sayer HG, Kroger M, Beyer J, Kiehl M, Klein SA, Schaefer-Eckart K et al. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant 2003; 31: 1089–1095.

    CAS  PubMed  Google Scholar 

  20. Herr AL, Labopin M, Blaise D, Milpied N, Potter M, Michallet M et al. HLA-identical sibling allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning compared to autologous peripheral blood stem cell transplantation for elderly patients with de novo acute myeloid leukemia. Leukemia 2007; 21: 129–135.

    CAS  PubMed  Google Scholar 

  21. Giralt S, Logan B, Rizzo D, Zhang MJ, Ballen K, Emmanouilides C et al. Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program. Biol Blood Marrow Transplant 2007; 13: 844–852.

    PubMed  Google Scholar 

  22. Chevallier P, Szydlo RM, Blaise D, Tabrizi R, Michallet M, Uzunov M et al. Reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation in patients over 60 years: a report from the SFGM-TC. Biol Blood Marrow Transplant 2012; 18: 289–294.

    PubMed  Google Scholar 

  23. Blaise D, Tabrizi R, Boher JM, Le Corroller-Soriano AG, Bay JO, Fegueux N et al. Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: Prospective clinical and socioeconomic evaluation. Cancer 2013; 119: 602–611.

    CAS  PubMed  Google Scholar 

  24. Baron F, Labopin M, Peniket A, Jindra P, Afanasyev B, Sanz MA et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer e-pub ahead of print 25 November 2014; doi:10.1002/cncr.29163.

    PubMed  Google Scholar 

  25. Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V et al. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant 2013; 19: 1340–1347.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Storb R, Gyurkocza B, Storer BE, Sorror ML, Blume K, Niederwieser D et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol 2013; 31: 1530–1538.

    Article  CAS  PubMed  Google Scholar 

  27. Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol 2010; 28: 2859–2867.

    PubMed  PubMed Central  Google Scholar 

  28. Chen YB, Coughlin E, Kennedy KF, Alyea EP, Armand P, Attar EC et al. Busulfan dose intensity and outcomes in reduced-intensity allogeneic peripheral blood stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia. Biol Blood Marrow Transplant 2013; 19: 981–987.

    PubMed  Google Scholar 

  29. Oran B, Giralt S, Saliba R, Hosing C, Popat U, Khouri I 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: 454–462.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. van Besien K, Stock W, Rich E, Odenike O, Godley LA, O'Donnell PH et al. Phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18: 913–921.

    CAS  PubMed  Google Scholar 

  31. Chevallier P, Labopin M, Buchholz S, Ganser A, Ciceri F, Lioure B et al. Clofarabine-containing conditioning regimen for allo-SCT in AML/ALL patients: a survey from the Acute Leukemia Working Party of EBMT. Eur J Haematol 2012; 89: 214–219.

    CAS  PubMed  Google Scholar 

  32. Andersson BS, Valdez BC, de Lima M, Wang X, Thall PF, Worth LL et al. Clofarabine+/−fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS. Biol Blood Marrow Transplant 2011; 17: 893–900.

    CAS  PubMed  Google Scholar 

  33. Pagel JM, Gooley TA, Rajendran J, Fisher DR, Wilson WA, Sandmaier BM et al. Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood 2009; 114: 5444–5453.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Mawad R, Gooley TA, Rajendran JG, Fisher DR, Gopal AK, Shields AT et al. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome. Biol Blood Marrow Transplant 2014; 20: 1363–1368.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Chevallier P, Labopin M, Socie G, Tabrizi R, Furst S, Lioure B et al. Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial. Haematologica 2014; 99: 1486–1491.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Nemecek ER, Guthrie KA, Sorror ML, Wood BL, Doney KC, Hilger RA et al. Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies. Biol Blood Marrow Transplant 2011; 17: 341–350.

    CAS  PubMed  Google Scholar 

  37. Gyurkocza B, Gutman J, Nemecek ER, Bar M, Milano F, Ramakrishnan A et al. Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia. Biol Blood Marrow Transplant 2014; 20: 549–555.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Alatrash G, de Lima M, Hamerschlak N, Pelosini M, Wang X, Xiao L et al. Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life. Biol Blood Marrow Transplant 2011; 17: 1490–1496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Casper J, Holowiecki J, Trenschel R, Wandt H, Schaefer-Eckart K, Ruutu T et al. Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning. Bone Marrow Transplant 2012; 47: 1171–1177.

    CAS  PubMed  Google Scholar 

  40. Bornhauser M, Storer B, Slattery JT, Appelbaum FR, Deeg HJ, Hansen J et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood 2003; 102: 820–826.

    PubMed  Google Scholar 

  41. Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW et al. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol 2013; 31: 701–709.

    CAS  PubMed  Google Scholar 

  42. Liu H, Zhai X, Song Z, Sun J, Xiao Y, Nie D et al. Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study. J Hematol Oncol 2013; 6: 15.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Oudin C, Chevallier P, Furst S, Guillaume T, El Cheikh J, Delaunay J et al. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies. Haematologica 2014; 99: 1762–1768.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Schmid C, Schleuning M, Hentrich M, Markl GE, Gerbitz A, Tischer J et al. High antileukemic efficacy of an intermediate intensity conditioning regimen for allogeneic stem cell transplantation in patients with high-risk acute myeloid leukemia in first complete remission. Bone Marrow Transplant 2008; 41: 721–727.

    CAS  PubMed  Google Scholar 

  45. Schmid C, Schleuning M, Tischer J, Holler E, Haude KH, Braess J et al. Early allo-SCT for AML with a complex aberrant karyotype—results from a prospective pilot study. Bone Marrow Transplant 2012; 47: 46–53.

    CAS  PubMed  Google Scholar 

  46. Schneidawind D, Federmann B, Faul C, Vogel W, Kanz L, Bethge WA . Allogeneic hematopoietic cell transplantation with reduced-intensity conditioning following FLAMSA for primary refractory or relapsed acute myeloid leukemia. Ann Hematol 2013; 92: 1389–1395.

    CAS  PubMed  Google Scholar 

  47. Pfeiffer T, Schleuning M, Mayer J, Haude KH, Tischer J, Buchholz S et al. Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse. Haematologica 2013; 98: 518–525.

    PubMed  PubMed Central  Google Scholar 

  48. Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood 2011; 117: 6963–6970.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 2012; 26: 2462–2468.

    CAS  PubMed  Google Scholar 

  50. Baron F, Labopin M, Blaise D, Lopez-Corral L, Vigouroux S, Craddock C et al. Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2014; 49: 389–396.

    CAS  PubMed  Google Scholar 

  51. Hamadani M, Blum W, Phillips G, Elder P, Andritsos L, Hofmeister C et al. Improved nonrelapse mortality and infection rate with lower dose of antithymocyte globulin in patients undergoing reduced-intensity conditioning allogeneic transplantation for hematologic malignancies. Biol Blood Marrow Transplant 2009; 15: 1422–1430.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Devillier R, Crocchiolo R, Castagna L, Furst S, El Cheikh J, Faucher C et al. The increase from 2.5 to 5 mg/kg of rabbit anti-thymocyte-globulin dose in reduced intensity conditioning reduces acute and chronic GVHD for patients with myeloid malignancies undergoing allo-SCT. Bone Marrow Transplant 2012; 47: 639–645.

    CAS  PubMed  Google Scholar 

  53. Bashir Q, Munsell MF, Giralt S, de Padua Silva L, Sharma M, Couriel D et al. Randomized phase II trial comparing two dose levels of thymoglobulin in patients undergoing unrelated donor hematopoietic cell transplant. Leukemia Lymphoma 2012; 53: 915–919.

    CAS  PubMed  Google Scholar 

  54. Wong FL, Francisco L, Togawa K, Bosworth A, Gonzales M, Hanby C et al. Long-term recovery after hematopoietic cell transplantation: predictors of quality-of-life concerns. Blood 2010; 115: 2508–2519.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Diez-Campelo M, Perez-Simon JA, Gonzalez-Porras JR, Garcia-Cecilia JM, Salinero M, Caballero MD et al. Quality of life assessment in patients undergoing reduced intensity conditioning allogeneic as compared to autologous transplantation: results of a prospective study. Bone Marrow Transplant 2004; 34: 729–738.

    CAS  PubMed  Google Scholar 

  56. Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA et al. Protective conditioning for acute graft-versus-host disease. N Engl J Med 2005; 353: 1321–1331.

    CAS  PubMed  Google Scholar 

  57. Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB et al. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood 2009; 114: 1099–1109.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Siddiqi T, Blaise D . Does antithymocyte globulin have a place in reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation? Hematology Am Soc Hematol Educ Program 2012; 2012: 246–250.

    PubMed  Google Scholar 

  59. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012; 367: 1487–1496.

    CAS  PubMed  Google Scholar 

  60. Champlin RE, Schmitz N, Horowitz MM, Chapuis B, Chopra R, Cornelissen JJ et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood 2000; 95: 3702–3709.

    CAS  PubMed  Google Scholar 

  61. Nagler A, Labopin M, Shimoni A, Mufti GJ, Cornelissen JJ, Blaise D et al. Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission: a retrospective analysis from the Acute Leukemia Working Party of EBMT. Eur J Haematol 2012; 89: 206–213.

    PubMed  Google Scholar 

  62. Nagler A, Labopin M, Shimoni A, Niederwieser D, Mufti GJ, Zander AR et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2012; 18: 1422–1429.

    PubMed  Google Scholar 

  63. Mielcarek M, Storer BE, Sandmaier BM, Sorror ML, Maloney DG, Petersdorf E et al. Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors. Biol Blood Marrow Transplant 2007; 13: 1499–1507.

    PubMed  PubMed Central  Google Scholar 

  64. Peffault de Latour R, Brunstein CG, Porcher R, Chevallier P, Robin M, Warlick E et al. Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia. Biol Blood Marrow Transplant 2013; 19: 1355–1360.

    PubMed  Google Scholar 

  65. Ho VT, Kim HT, Liney D, Milford E, Gribben J, Cutler C et al. HLA-C mismatch is associated with inferior survival after unrelated donor non-myeloablative hematopoietic stem cell transplantation. Bone Marrow Transplant 2006; 37: 845–850.

    CAS  PubMed  Google Scholar 

  66. Nakamae H, Storer BE, Storb R, Storek J, Chauncey TR, Pulsipher MA et al. Low-dose total body irradiation and fludarabine conditioning for HLA class I-mismatched donor stem cell transplantation and immunologic recovery in patients with hematologic malignancies: a multicenter trial. Biol Blood Marrow Transplant 2010; 16: 384–394.

    CAS  PubMed  Google Scholar 

  67. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    CAS  PubMed  Google Scholar 

  68. Rocha V, Mohty M, Gluckman E, Rio B et al, Eurocord, Reduced-Intensity Conditioning Subcommittee of the Acute Leukaemia Working Party. Reduced-intensity conditioning regimens before unrelated cord blood transplantation in adults with acute leukaemia and other haematological malignancies. Curr Opin Oncol 2009; 21 (Suppl 1): S31–S34.

    PubMed  Google Scholar 

  69. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood 2011; 118: 282–288.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.

    CAS  PubMed  Google Scholar 

  71. Rizzieri DA, Koh LP, Long GD, Gasparetto C, Sullivan KM, Horwitz M et al. Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol 2007; 25: 690–697.

    CAS  PubMed  Google Scholar 

  72. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Kekre N, Antin JH . Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood 2014; 124: 334–343.

    CAS  PubMed  Google Scholar 

  74. Mohty M, Kuentz M, Michallet M, Bourhis JH, Milpied N, Sutton L et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100: 3128–3134.

    CAS  PubMed  Google Scholar 

  75. Ringden O, Labopin M, Ehninger G, Niederwieser D, Olsson R, Basara N et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol 2009; 27: 4570–4577.

    PubMed  Google Scholar 

  76. Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.

    CAS  PubMed  Google Scholar 

  77. Perez-Simon JA, Diez-Campelo M, Martino R, Brunet S, Urbano A, Caballero MD et al. Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation. Br J Haematol 2005; 130: 394–403.

    PubMed  Google Scholar 

  78. Couriel DR, Saliba RM, Giralt S, Khouri I, Andersson B, de Lima M et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant 2004; 10: 178–185.

    PubMed  Google Scholar 

  79. Luger SM, Ringden O, Zhang MJ, Perez WS, Bishop MR, Bornhauser M et al. Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS. Bone Marrow Transplant 2012; 47: 203–211.

    CAS  PubMed  Google Scholar 

  80. Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb HJ et al. 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.

    CAS  PubMed  Google Scholar 

  81. Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004; 104: 1550–1558.

    CAS  PubMed  Google Scholar 

  82. Martino R, de Wreede L, Fiocco M, van Biezen A, von dem Borne PA, Hamladji RM et al. Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with <10% BM blasts: a report from EBMT. Bone Marrow Transplant 2013; 48: 761–770.

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  84. Khera N, Emmert A, Storer BE, Sandmaier BM, Alyea EP, Lee SJ . Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens. Oncologist 2014; 19: 639–644.

    PubMed  PubMed Central  Google Scholar 

  85. Nakamae H, Kirby KA, Sandmaier BM, Norasetthada L, Maloney DG, Maris MB et al. Effect of conditioning regimen intensity on CMV infection in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009; 15: 694–703.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C 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: 961–968.

    CAS  PubMed  Google Scholar 

  87. Castermans E, Hannon M, Dutrieux J, Humblet-Baron S, Seidel L, Cheynier R et al. Thymic recovery after allogeneic hematopoietic cell transplantation with non-myeloablative conditioning is limited to patients younger than 60 years of age. Haematologica 2011; 96: 298–306.

    CAS  PubMed  Google Scholar 

  88. Tauro S, Craddock C, Peggs K, Begum G, Mahendra P, Cook G 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: 9387–9393.

    CAS  PubMed  Google Scholar 

  89. Nakamae H, Storer B, Sandmaier BM, Maloney DG, Davis C, Corey L et al. Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs. Haematologica 2011; 96: 1838–1845.

    PubMed  PubMed Central  Google Scholar 

  90. Silva Lde P, Patah PA, Saliba RM, Szewczyk NA, Gilman L, Neumann J et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica 2010; 95: 1183–1190.

    PubMed  Google Scholar 

  91. Junghanss C, Marr KA, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Incidence and outcome of bacterial and fungal infections following nonmyeloablative compared with myeloablative allogeneic hematopoietic stem cell transplantation: a matched control study. Biol Blood Marrow Transplant 2002; 8: 512–520.

    PubMed  Google Scholar 

  92. Weissinger F, Sandmaier BM, Maloney DG, Bensinger WI, Gooley T, Storb R . Decreased transfusion requirements for patients receiving nonmyeloablative compared with conventional peripheral blood stem cell transplants from HLA-identical siblings. Blood 2001; 98: 3584–3588.

    CAS  PubMed  Google Scholar 

  93. Fukuda T, Hackman RC, Guthrie KA, Sandmaier BM, Boeckh M, Maris MB et al. Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. Blood 2003; 102: 2777–2785.

    PubMed  Google Scholar 

  94. Parikh CR, Schrier RW, Storer B, Diaconescu R, Sorror ML, Maris MB et al. Comparison of ARF after myeloablative and nonmyeloablative hematopoietic cell transplantation. Am J Kidney Dis 2005; 45: 502–509.

    PubMed  Google Scholar 

  95. Hogan WJ, Maris M, Storer B, Sandmaier BM, Maloney DG, Schoch HG et al. Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients. Blood 2004; 103: 78–84.

    CAS  PubMed  Google Scholar 

  96. Shimoni A, Shem-Tov N, Chetrit A, Volchek Y, Tallis E, Avigdor A et al. Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning; the incidence is not reduced. Leukemia 2013; 27: 829–835.

    CAS  PubMed  Google Scholar 

  97. Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol 2012; 13: 1035–1044.

    PubMed  Google Scholar 

  98. Junghanss C, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. Blood 2002; 99: 1978–1985.

    CAS  PubMed  Google Scholar 

  99. Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 2003; 102: 827–833.

    CAS  PubMed  Google Scholar 

  100. Bevans MF, Marden S, Leidy NK, Soeken K, Cusack G, Rivera P et al. Health-related quality of life in patients receiving reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2006; 38: 101–109.

    CAS  PubMed  Google Scholar 

  101. Andersson I, Ahlberg K, Stockelberg D, Brune M, Persson LO . Health-related quality of life in patients undergoing allogeneic stem cell transplantation after reduced intensity conditioning versus myeloablative conditioning. Cancer Nurs 2009; 32: 325–334.

    PubMed  Google Scholar 

  102. Gupta V, Panzarella T, Li L, Khan J, Sharma A, Lipton JH et al. A prospective study comparing the outcomes and health-related quality of life in adult patients with myeloid malignancies undergoing allogeneic transplantation using myeloablative or reduced-intensity conditioning. Biol Blood Marrow Transplant 2012; 18: 113–124.

    PubMed  Google Scholar 

  103. McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol 2010; 28: 1878–1887.

    PubMed  PubMed Central  Google Scholar 

  104. Sorror ML, Giralt S, Sandmaier BM, De Lima M, Shahjahan M, Maloney DG 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: 4606–4613.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Wong R, Shahjahan M, Wang X, Thall PF, De Lima M, Khouri I et al. Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant 2005; 11: 108–114.

    PubMed  Google Scholar 

  106. Brunner AM, Kim HT, Coughlin E, Alyea EP 3rd, Armand P, Ballen KK et al. Outcomes in patients age 70 or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant 2013; 19: 1374–1380.

    PubMed  Google Scholar 

  107. Sorror ML, Sandmaier BM, Storer BE, Franke GN, Laport GG, Chauncey TR et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA 2011; 306: 1874–1883.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 2007; 25: 4246–4254.

    PubMed  Google Scholar 

  109. Lim ZY, Ingram W, Brand R, Ho A, Kenyon M, Devereux S et al. Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML. Bone Marrow Transplant 2010; 45: 633–639.

    CAS  PubMed  Google Scholar 

  110. Boehm A, Sperr WR, Leitner G, Worel N, Oehler L, Jaeger E et al. Comorbidity predicts survival in myelodysplastic syndromes or secondary acute myeloid leukaemia after allogeneic stem cell transplantation. Eur J Clin Invest 2008; 38: 945–952.

    CAS  PubMed  Google Scholar 

  111. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Barba P, Martino R, Perez-Simon JA, Fernandez-Aviles F, Castillo N, Pinana JL et al. Combination of the Hematopoietic Cell Transplantation Comorbidity Index and the European Group for Blood and Marrow Transplantation score allows a better stratification of high-risk patients undergoing reduced-toxicity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2014; 20: 66–72.

    PubMed  Google Scholar 

  113. Versluis J, Labopin M, Niederwieser D, Socie G, Schlenk RF, Milpied N et al. Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission. Leukemia 2014; 29: 51–57.

    PubMed  Google Scholar 

  114. Sorror ML, Storb RF, Sandmaier BM, Maziarz RT, Pulsipher MA, Maris MB et al. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol 2014; 32: 3249–3256.

    PubMed  PubMed Central  Google Scholar 

  115. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME et al. Validation and refinement of the disease risk index for allogeneic stem cell transplantation: a study from the CIBMTR. Blood 2014; 123: 3664–3671.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. van Besien K, Artz A, Smith S, Cao D, Rich S, Godley L 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.

    CAS  PubMed  Google Scholar 

  117. Wong R, Giralt SA, Martin T, Couriel DR, Anagnostopoulos A, Hosing C 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.

    CAS  PubMed  Google Scholar 

  118. Michallet M, Bilger K, Garban F, Attal M, Huyn A, Blaise D et al. Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome. J Clin Oncol 2001; 19: 3340–3349.

    CAS  PubMed  Google Scholar 

  119. Craddock C, Nagra S, Peniket A, Brookes C, Buckley L, Nikolousis E et al. Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 2010; 95: 989–995.

    PubMed  Google Scholar 

  120. Chevallier P, Labopin M, Milpied N, Cornelissen JJ, Blaise D, Petersen E et al. Impact of cytogenetics risk on outcome after reduced intensity conditioning allo-SCT from an HLA-identical sibling for patients with AML in first CR: a report from the acute leukemia working party of EBMT. Bone Marrow Transplant 2012; 47: 1442–1447.

    CAS  PubMed  Google Scholar 

  121. Baron F, Maris MB, Storer BE, Sandmaier BM, Panse JP, Chauncey TR et al. High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia 2005; 19: 822–828.

    CAS  PubMed  Google Scholar 

  122. Perez-Simon JA, Diez-Campelo M, Martino R, Sureda A, Caballero D, Canizo C et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood 2003; 102: 1108–1113.

    CAS  PubMed  Google Scholar 

  123. Torlen J, Ringden O, Le Rademacher J, Batiwalla M, Chen J, Erkers T et al. Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 2014; 20: 1418–1425.

    PubMed  PubMed Central  Google Scholar 

  124. Reshef R, Huffman AP, Gao A, Sell M, Luskin M, Luger S et al. CD8 cell dose in peripheral blood stem-cell grafts correlates with relapse and survival after reduced intensity allogeneic stem-cell transplantation. Blood 2014; 124: 1260.

    Google Scholar 

  125. Cao TM, Shizuru JA, Wong RM, Sheehan K, Laport GG, Stockerl-Goldstein KE et al. Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose. Blood 2005; 105: 2300–2306.

    CAS  PubMed  Google Scholar 

  126. Mohty M, Bagattini S, Chabannon C, Faucher C, Bardou VJ, Bilger K et al. CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Exp Hematol 2004; 32: 1097–1102.

    CAS  PubMed  Google Scholar 

  127. Reshef R, Hexner EO, Loren AW, Frey NV, Stadtmauer EA, Luger SM et al. Early donor chimerism levels predict relapse and survival after allogeneic stem-cell transplantation with reduced intensity conditioning. Biol Blood Marrow Transplant 2014; 20: 1758–1766.

    PubMed  PubMed Central  Google Scholar 

  128. Koreth J, Kim HT, Nikiforow S, Milford EL, Armand P, Cutler C et al. Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival. Biol Blood Marrow Transplant 2014; 20: 1516–1521.

    PubMed  PubMed Central  Google Scholar 

  129. Paietta E . Minimal residual disease in acute myeloid leukemia: coming of age. Hematology Am Soc Hematol Educ Program 2012; 2012: 35–42.

    PubMed  Google Scholar 

  130. Hokland P, Ommen HB . Towards individualized follow-up in adult acute myeloid leukemia in remission. Blood 2011; 117: 2577–2584.

    CAS  PubMed  Google Scholar 

  131. Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia 2012; 26: 381–389.

    CAS  PubMed  Google Scholar 

  132. Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R et al. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood 2012; 119: 1599–1606.

    CAS  PubMed  Google Scholar 

  133. Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A et al. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol 2010; 28: 405–411.

    PubMed  Google Scholar 

  134. Oran B, Giralt S, Couriel D, Hosing C, Shpall EJ, de Meis E et al. Treatment of AML and MDS relapsing after reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation. Leukemia 2007; 21: 2540–2544.

    CAS  PubMed  Google Scholar 

  135. Bethge WA, Storer BE, Maris MB, Flowers ME, Maloney DG, Chauncey TR et al. Relapse or progression after hematopoietic cell transplantation using nonmyeloablative conditioning: effect of interventions on outcome. Exp Hematol 2003; 31: 974–980.

    PubMed  Google Scholar 

  136. Pollyea DA, Artz AS, Stock W, Daugherty C, Godley L, Odenike OM et al. Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2007; 40: 1027–1032.

    CAS  PubMed  Google Scholar 

  137. Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 2007; 25: 4938–4945.

    CAS  PubMed  Google Scholar 

  138. Bethge WA, Hegenbart U, Stuart MJ, Storer BE, Maris MB, Flowers ME et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood 2004; 103: 790–795.

    CAS  PubMed  Google Scholar 

  139. Porter DL, Roth MS, Lee SJ, McGarigle C, Ferrara JL, Antin JH . Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 18: 975–980.

    CAS  PubMed  Google Scholar 

  140. Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    PubMed  Google Scholar 

  141. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  142. de Lima M, Giralt S, Thall PF, de Padua Silva L, Jones RB, Komanduri K et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer 2010; 116: 5420–5431.

    CAS  PubMed  Google Scholar 

  143. Choi J, Ritchey J, Prior JL, Holt M, Shannon WD, Deych E et al. In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood 2010; 116: 129–139.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 2012; 119: 3361–3369.

    CAS  PubMed  Google Scholar 

  145. de Lima M, Parmar S, Chen JJ, Giralt SA, Rondon G, Popat UR et al. Low dose azacitidine (AZA) reduces the incidence of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). ASH Annual Meeting Abstracts 2012; 120: 742.

    Google Scholar 

  146. Sockel K, Bornhaeuser M, Mischak-Weissinger E, Trenschel R, Wermke M, Unzicker C et al. Lenalidomide maintenance after allogeneic HSCT seems to trigger acute graft-versus-host disease in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia and del(5q): results of the LENAMAINT trial. Haematologica 2012; 97: e34–e35.

    PubMed  PubMed Central  Google Scholar 

  147. Ho VT, Vanneman M, Kim H, Sasada T, Kang YJ, Pasek M et al. Biologic activity of irradiated, autologous, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation. Proc Natl Acad Sci USA 2009; 106: 15825–15830.

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Kumar AJ, Hexner EO, Frey NV, Luger SM, Loren AW, Reshef R et al. Pilot study of prophylactic ex vivo costimulated donor leukocyte infusion after reduced-intensity conditioned allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19: 1094–1101.

    PubMed  Google Scholar 

  149. Massenkeil G, Nagy M, Lawang M, Rosen O, Genvresse I, Geserick G et al. Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved. Bone Marrow Transplant 2003; 31: 339–345.

    CAS  PubMed  Google Scholar 

  150. Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Zoumbos NC et al. High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transplant 2013; 19: 75–81.

    CAS  PubMed  Google Scholar 

  151. Shimoni A, Hardan I, Shem-Tov N, Yeshurun M, Yerushalmi R, Avigdor A 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: 322–328.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to acknowledge the Center for International Blood and Marrow Transplant Research for providing data on the use of reduced-intensity transplants in AML. This work was supported in part by the Margie and Andy Rooke Fund for Leukemia Research, The Greg Wolf Fund and by grants from the National Cancer Institute (CA178202), the Conquer Cancer Foundation (Career Development Award), the National Marrow Donor Program (Amy Strelzer Manasevit Award) and the Commonwealth of Pennsylvania (CURE Program).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to R Reshef or D L Porter.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reshef, R., Porter, D. Reduced-intensity conditioned allogeneic SCT in adults with AML. Bone Marrow Transplant 50, 759–769 (2015). https://doi.org/10.1038/bmt.2015.7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.7

This article is cited by

Search

Quick links