Table of Contents Author Guidelines Submit a Manuscript
Journal of Oncology
Volume 2010 (2010), Article ID 943823, 11 pages
http://dx.doi.org/10.1155/2010/943823
Review Article

Challenges in Treating Older Patients with Acute Myeloid Leukemia

Division of Hematology/BMT Unit, Patras University Hospital, Patras, Greece

Received 31 December 2009; Accepted 27 March 2010

Academic Editor: Thomas R. Chauncey

Copyright © 2010 Lagadinou D. Eleni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. A. Sekeres, R. M. Stone, D. Zahrieh et al., “Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome,” Leukemia, vol. 18, no. 4, pp. 809–816, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. J. Menzin, K. Lang, C. C. Earle, D. Kerney, and R. Mallick, “The outcomes and costs of acute myeloid leukemia among the elderly,” Archives of Internal Medicine, vol. 162, no. 14, pp. 1597–1603, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. B. Behringer, J. A. Pitako, R. Kunzmann et al., “Prognosis of older patients with acute myeloid leukemia receiving either induction or noncurative treatment: a single-center retrospective study,” Annals of Hematology, vol. 82, no. 7, pp. 381–389, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. A. Pulsoni, L. Pagano, R. Latagliata et al., “Survival of elderly patients with acute myeloid leukemia,” Haematologica, vol. 89, no. 3, pp. 296–302, 2004. View at Google Scholar · View at Scopus
  5. E. H. Estey, “Treatment of acute myeloid leukemia,” Haematologica, vol. 94, no. 1, pp. 10–16, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. W. Hiddemann, W. Kern, C. Schoch et al., “Management of acute myeloid leukemia in elderly patients,” Journal of Clinical Oncology, vol. 17, no. 11, pp. 3569–3576, 1999. View at Google Scholar · View at Scopus
  7. H. D. Klepin and L. Balducci, “Acute myelogenous leukemia in older adults,” Oncologist, vol. 14, no. 3, pp. 222–232, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. C. P. Leith, K. J. Kopecky, J. Godwin et al., “Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group Study,” Blood, vol. 89, no. 9, pp. 3323–3329, 1997. View at Google Scholar · View at Scopus
  9. P. J. Fialkow, J. W. Singer, and W. H. Raskind, “Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia,” The New England Journal of Medicine, vol. 317, no. 8, pp. 468–473, 1987. View at Google Scholar · View at Scopus
  10. C. S. Wilson, G. S. Davidson, S. B. Martin et al., “Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction,” Blood, vol. 108, no. 2, pp. 685–696, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. F. Ferrara and A. Pinto, “Acute myeloid leukemia in the elderly: current therapeutic results and perspectives for clinical research,” Reviews on Recent Clinical Trials, vol. 2, no. 1, pp. 33–41, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. B. D. Cheson, D. M. Jasperse, R. Simon, and M. A. Friedman, “A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes,” Journal of Clinical Oncology, vol. 4, no. 12, pp. 1857–1864, 1986. View at Google Scholar · View at Scopus
  13. A. K. Burnett, D. Milligan, A. G. Prentice et al., “A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment,” Cancer, vol. 109, no. 6, pp. 1114–1124, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. A. Wahlin, P. Hornsten, and H. Jonsson, “Remission rate and survival in acute myeloid leukemia: impact of selection and chemotherapy,” European Journal of Haematology, vol. 46, no. 4, pp. 240–247, 1991. View at Google Scholar · View at Scopus
  15. S. Fröhling, R. F. Schlenk, S. Kayser et al., “Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B,” Blood, vol. 108, no. 10, pp. 3280–3288, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. T. Prebet, N. Boissel, S. Reutenauer et al., “Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup,” Journal of Clinical Oncology, vol. 27, no. 28, pp. 4747–4753, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. D. A. Breems, W. L. J. Van Putten, G. E. de Greef et al., “Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype,” Journal of Clinical Oncology, vol. 26, no. 29, pp. 4791–4797, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. R. O'Donnell, F. R. Appelbaum, M. R. Baer et al., “Acute myeloid leukemia: clinical practice guidelines in oncology,” Journal of the National Comprehensive Cancer Network, vol. 4, no. 1, pp. 16–36, 2006. View at Google Scholar · View at Scopus
  19. E. Morra, G. Barosi, A. Bosi et al., “Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation,” Haematologica, vol. 94, no. 1, pp. 102–112, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. D. Grimwade, H. Walker, G. Harrison et al., “The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial,” Blood, vol. 98, no. 5, pp. 1312–1320, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. V. Gupta, K. Chun, Q.-L. Yi et al., “Disease biology rather than age is the most important determinant of survival of patients 60 years with acute myeloid leukemia treated with uniform intensive therapy,” Cancer, vol. 103, no. 10, pp. 2082–2090, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. T. Buchner, W. E. Berdel, C. Haferlach et al., “Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the german acute myeloid leukemia cooperative group,” Journal of Clinical Oncology, vol. 27, no. 1, pp. 61–69, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. R. F. Schlenk, K. Döhner, M. Kneba et al., “Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B,” Haematologica, vol. 94, no. 1, pp. 54–60, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. M. A. Sekeres, P. Elson, M. E. Kalaycio et al., “Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients,” Blood, vol. 113, no. 1, pp. 28–36, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. F. R. Appelbaum, H. Gundacker, D. R. Head et al., “Age and acute myeloid leukemia,” Blood, vol. 107, no. 9, pp. 3481–3485, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. H. Kantarjian, S. O'Brisn, J. Cortes et al., “Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome,” Cancer, vol. 106, no. 5, pp. 1090–1098, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. J.-V. Malfuson, A. Etienne, P. Turlure et al., “Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia,” Haematologica, vol. 93, no. 12, pp. 1806–1813, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. B. Lowenberg, R. Zittoun, H. Kerkhofs et al., “On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group,” Journal of Clinical Oncology, vol. 7, no. 9, pp. 1268–1274, 1989. View at Google Scholar · View at Scopus
  29. G. Juliusson, P. Antunovic, Å. Derolf et al., “Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry,” Blood, vol. 113, no. 18, pp. 4179–4187, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. T. Büchner, W. Hiddemann, W. Berdel et al., “Acute myeloid leukemia: treatment over 60,” Reviews in Clinical and Experimental Hematology, vol. 6, no. 1, pp. 46–59, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. J. K. H. Rees, R. G. Gray, and K. Wheatley, “Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study,” British Journal of Haematology, vol. 94, no. 1, pp. 89–98, 1996. View at Google Scholar · View at Scopus
  32. B. Lowenberg, G. J. Ossenkoppele, W. van Putten et al., “High-dose daunorubicin in older patients with acute myeloid leukemia,” The New England Journal of Medicine, vol. 361, no. 13, pp. 1235–1248, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. J. K. Weick, K. J. Kopecky, F. R. Appelbaum et al., “A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study,” Blood, vol. 88, no. 8, pp. 2841–2851, 1996. View at Google Scholar · View at Scopus
  34. T. Buchner, W. Hiddemann, W. E. Berdel et al., “6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group,” Journal of Clinical Oncology, vol. 21, no. 24, pp. 4496–4504, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. G. Schiller and M. Lee, “Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for older patients with acute myelogenous leukemia,” Leukemia and Lymphoma, vol. 25, no. 1-2, pp. 111–119, 1997. View at Google Scholar
  36. J. Reiffers, F. Huguet, A.-M. Stoppa et al., “A prospective randomized trial of idarubicin vs daunorubicin in combination chemotherapy for acute myelogenous leukemia of the age group 55 to 75,” Leukemia, vol. 10, no. 3, pp. 389–395, 1996. View at Google Scholar · View at Scopus
  37. M. S. Tallman, D. G. Gilliland, and J. M. Rowe, “Drug therapy for acute myeloid leukemia,” Blood, vol. 106, no. 4, pp. 1154–1163, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. J. Miyauchi, C. A. Kelleher, C. Wang, S. Minkin, and E. A. McCulloch, “Growth factors influence the sensitivity of leukemic stem cells to cytosine arabinoside in culture,” Blood, vol. 73, no. 5, pp. 1272–1278, 1989. View at Google Scholar · View at Scopus
  39. S. Amadori, S. Suciu, U. Jehn et al., “Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study,” Blood, vol. 106, no. 1, pp. 27–34, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. H. Dombret, C. Chastang, P. Fenaux et al., “A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia,” The New England Journal of Medicine, vol. 332, no. 25, pp. 1678–1683, 1995. View at Publisher · View at Google Scholar · View at Scopus
  41. D. W. Milligan, K. Wheatley, T. Littlewood, J. I. O. Craig, and A. K. Burnett, “Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial,” Blood, vol. 107, no. 12, pp. 4614–4622, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. K. Wheatley, A. H. Goldstone, T. Littlewood, A. Hunter, and A. K. Burnett, “Randomized placebo-controlled trial of granulocyte colony stimulating factor (G-CSF) as supportive care after induction chemotherapy in adult patients with acute myeloid leukaemia: a study of the United Kingdom Medical Research Council Adult Leukaemia Working Party,” British Journal of Haematology, vol. 146, no. 1, pp. 54–63, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. B. Nervi, P. Ramirez, M. P. Rettig et al., “Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100,” Blood, vol. 113, no. 24, pp. 6206–6214, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. G. L. Uy, M. P. Rettig, and K. M. Mcfarland, “Mobilization and chemosensitization of AML with the CXCR4 antagonist plerixafor (AMD3100): a phase I/II study of AMD3100+MEC in patients with relapsed or refractory disease,” Blood, vol. 112, no. 11, 2008, abstract 1944. View at Google Scholar
  45. P. Matsouka, M. Pagoni, P. Zikos et al., “Addition of cyclosporin-A to chemotherapy in secondary (post-MDS) AML in the elderly. A multicenter randomized trial of the Leukemia Working Group of the Hellenic Society of Hematology,” Annals of Hematology, vol. 85, no. 4, pp. 250–256, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. A. F. List, K. J. Kopecky, C. L. Willman et al., “Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study,” Blood, vol. 98, no. 12, pp. 3212–3220, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. P. L. Greenberg, S. J. Lee, R. Advani et al., “Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995),” Journal of Clinical Oncology, vol. 22, no. 6, pp. 1078–1086, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. H. P. Erba, “Prognostic factors in elderly patients with AML and the implications for treatment,” Hematology, pp. 420–428, 2007. View at Google Scholar
  49. A. K. Burnett, D. Milligan, A. Goldstone et al., “The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial,” British Journal of Haematology, vol. 145, no. 3, pp. 318–332, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. L. D. Cripe, X. Li, M. Litzow et al., “A randomized, placebocontrolled, double blind trial of the MDR modulator zosuquidar, during conventional induction and postremission therapy for pts > 60 years of age with newlydiagnosed acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (HR-MDS): ECOG 3999,” Blood, vol. 108, article 129a, 2006. View at Google Scholar
  51. A. K. Burnett, M. Baccarani, P. Johnson, J. Yin, and N. Russell, “Clofarabine in previously untreated elderly (>65 yrs) AML patients with an unfavourable cytogenetic profile who are considered unfit for standard intensive chemotherapy,” Blood, vol. 24, no. 18S, 2006, abstract 6513. View at Google Scholar
  52. H. P. Erba, H. M. Kantarjian, D. Claxton et al., “Phase II study of single agent clofarabine in previously untreated older adult patients with acute myelogenous leukemia (AML) unlikely to benefit from standard induction chemotherapy,” Journal of Clinical Oncology, no. 20S, 2008, abstract 7025. View at Google Scholar
  53. S. Faderl, F. Ravandi, X. Huang et al., “A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome,” Blood, vol. 112, no. 5, pp. 1638–1645, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. J. E. Karp, D. Rizzieri, N. Vey et al., “Cloretazine is an effective induction therapy in elderly patients (pts) with poor-risk de novo AML,” Journal of Clinical Oncology, vol. 24, no. 18S, 2006. View at Google Scholar
  55. J. E. Karp, D. Rizzieri, N. Vey et al., “Cloretazine is an effective induction therapy in elderly patients (pts) with poor-risk de novo AML,” Journal of Clinical Oncology, vol. 24, no. 18S, 2006. View at Google Scholar
  56. M. Daskalakis, T. T. Nguyen, C. Nguyen et al., “Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-aza-2-deoxycytidine (decitabine) treatment,” Blood, vol. 100, no. 8, pp. 2957–2964, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. E. Kaminskas, A. Farrell, S. Abraham et al., “Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes,” Clinical Cancer Research, vol. 11, no. 10, pp. 3604–3608, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. P. Fenaux, G. J. Mufti, E. Hellstrom-Lindberg et al., “Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study,” The Lancet Oncology, vol. 10, no. 3, pp. 223–232, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. P. Fenaux, G. J. Mufti, E. Hellström-Lindberg et al., “Azacitidine prolongs overall survival (OS) and reduces infections and hospitalizations in patients (Pts) with WHO-defined acute myeloid leukemia (AML) compared with conventional care regimens (CCR),” Blood, vol. 112, 2008, abstract 3636. View at Google Scholar
  60. F. Ravandi, J.-P. Issa, G. Garcia-Manero et al., “Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities,” Cancer, vol. 115, no. 24, pp. 5746–5751, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. M. Lubbert, B. Ruter, R. Claus et al., “Continued low-dose decitabine (DAC) is an active first-line treatment in all cytogenetic subgroups of older AML patients: results of the FR00331 multicenter phase II study,” Blood, vol. 110, no. 95a, 2007, abstract 300. View at Google Scholar
  62. R. A. Larson, E. L. Sievers, E. A. Stadtmauer et al., “Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence,” Cancer, vol. 104, no. 7, pp. 1442–1452, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. J. Doyen, A. Italiano, F. Peyrade, C. Bouyer, and A. Thyss, “Gemtuzumab ozogamicin plus cytarabine in elderly patients with relapsed or refractory acute myeloid leukaemia,” British Journal of Haematology, vol. 141, no. 5, pp. 744–745, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. L. Fianchi, L. Pagano, F. Leoni et al., “Gemtuzumab ozogamicin, cytosine arabinoside, G-CSF combination (G-AraMy) in the treatment of elderly patients with poor-prognosis acute myeloid leukemia,” Annals of Oncology, vol. 19, no. 1, pp. 128–134, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. S. Amadori, S. Suciu, R. Willemze et al., “Sequential administration of gemtuzumab ozogamicin and conventional chemotherapy as first line therapy in elderly patients with acute myeloid leukemia: a phase II study (AML-15) of the EORTC and GIMEMA leukemia groups,” Haematologica, vol. 89, no. 8, pp. 950–956, 2004. View at Google Scholar · View at Scopus
  66. M. Clavio, L. Vignolo, A. Albarello et al., “Adding low-dose gemtuzumab ozogamicin to fludarabine, Ara-C and idarubicin (MY-FLAI) may improve disease-free and overall survival in elderly patients with non-M3 acute myeloid leukaemia: results of a prospective, pilot, multi-centre trial and comparison with a historical cohort of patients,” British Journal of Haematology, vol. 138, no. 2, pp. 186–195, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. S. Nand, J. Godwin, S. Smith et al., “Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial,” Leukemia and Lymphoma, vol. 49, no. 11, pp. 2141–2147, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. J.-L. Harousseau, G. Martinelli, W. W. Jedrzejczak et al., “A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older,” Blood, vol. 114, no. 6, pp. 1166–1173, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. S. Knapper, A. K. Burnett, T. Littlewood et al., “A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy,” Blood, vol. 108, no. 10, pp. 3262–3270, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. H. J. Deeg, H. M. Shulman, J. E. Anderson et al., “Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age,” Blood, vol. 95, no. 4, pp. 1188–1194, 2000. View at Google Scholar · View at Scopus
  71. W. Du, R. Dansey, E. M. Abella et al., “Successful allogeneic bone marrow transplantation in selected patients over 50 years of age—a single institution's experience,” Bone Marrow Transplantation, vol. 21, no. 10, pp. 1043–1047, 1998. View at Google Scholar · View at Scopus
  72. H. Bertz, K. Potthoff, and J. Finke, “Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia,” Journal of Clinical Oncology, vol. 21, no. 8, pp. 1480–1484, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. E. Estey, M. de Lima, R. Tibes et al., “Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS),” Blood, vol. 109, no. 4, pp. 1395–1400, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. J. Finke and A. Nagler, “Viewpoint: what is the role of allogeneic haematopoietic cell transplantation in the era of reduced-intensity conditioning—is there still an upper age limit? A focus on myeloid neoplasia,” Leukemia, vol. 21, no. 7, pp. 1357–1362, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  75. U. Hegenbart, D. Niederwieser, B. M. Sandmaier et al., “Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors,” Journal of Clinical Oncology, vol. 24, no. 3, pp. 444–453, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  76. A. Y. L. Ho, A. Pagliuca, M. Kenyon 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, vol. 104, no. 6, pp. 1616–1623, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. N. Kroger, M. Bornhäuser, G. Ehninger et al., “Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia,” Annals of Hematology, vol. 82, no. 6, pp. 336–342, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. M. B. Maris, D. Niederwieser, B. M. Sandmaier et al., “HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies,” Blood, vol. 102, no. 6, pp. 2021–2030, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. R. Marks, K. Potthoff, J. Hahn et al., “Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies,” Blood, vol. 112, no. 2, pp. 415–425, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. M. Mohty, H. de Lavallade, J. El-Cheikh et al., “Reduced intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia: long term results of a ‘donor’ versus ‘no donor’ comparison,” Leukemia, vol. 23, no. 1, pp. 194–196, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. O. Ringden, M. Labopin, G. Ehninger et al., “Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia,” Journal of Clinical Oncology, vol. 27, no. 27, pp. 4570–4577, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. A. Shimoni, N. Kröger, T. Zabelina et al., “Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age>55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning,” Leukemia, vol. 19, no. 1, pp. 7–12, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  83. S. Slavin, A. Nagler, E. Naparstek 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, vol. 91, no. 3, pp. 756–763, 1998. View at Google Scholar · View at Scopus
  84. A. Spyridonidis, H. Bertz, G. Ihorst, C. Grüllich, and J. Finke, “Hematopoietic cell transplantation from unrelated donors as an effective therapy for older patients (60 years) with active myeloid malignancies,” Blood, vol. 105, no. 10, pp. 4147–4148, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  85. R. Wong, S. A. Giralt, T. Martin et al., “Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years,” Blood, vol. 102, no. 8, pp. 3052–3059, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. C. Schmid, M. Schleuning, G. Ledderose, J. Tischer, and H.-J. Kolb, “Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome,” Journal of Clinical Oncology, vol. 23, no. 24, pp. 5675–5687, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. N. H. Russell, J. I. Byrne, and S. P. Robinson, “Defining conditioning regimens for BMT-recognition of “regimens of intermediate intensity”,” Biology of Blood and Marrow Transplantation, vol. 15, no. 7, pp. 890–891, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. M. de Lima, A. Anagnostopoulos, M. Munsell 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, vol. 104, no. 3, pp. 865–872, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  89. A. Shimoni, I. Hardan, N. Shem-Tov et al., “Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: The role of dose intensity,” Leukemia, vol. 20, no. 2, pp. 322–328, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. M. de Lima, D. Couriel, P. F. Thall 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, vol. 104, no. 3, pp. 857–864, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  91. J. Casper, W. Knauf, T. Kiefer et al., “Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation,” Blood, vol. 103, no. 2, pp. 725–731, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. F. B. Petersen and C. D. Ford, “Maximum supportive care, standard conditioning and allogeneic stem cell transplantation for elderly patients with acute myelogenous leukemia,” Current Opinion in Oncology, vol. 21, supplement 1, pp. S7–S9, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. M. E. D. Flowers, F. Traina, B. Storer et al., “Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning,” Bone Marrow Transplantation, vol. 35, no. 3, pp. 277–282, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. J. Schetelig, M. Bornhäuser, C. Schmid et al., “Matched unrelated or matched sibling donors result in comparable survival after allogeneic stem-cell transplantation in elderly patients with acute myeloid leukemia: a report from the cooperative German transplant study group,” Journal of Clinical Oncology, vol. 26, no. 32, pp. 5183–5191, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  95. H. G. Sayer, M. Kröger, J. Beyer 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 Transplantation, vol. 31, no. 12, pp. 1089–1095, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. J. E. Anderson, T. A. Gooley, G. Schoch et al., “Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy,” Blood, vol. 89, no. 7, pp. 2578–2585, 1997. View at Google Scholar · View at Scopus
  97. E. Jabbour, S. Giralt, H. Kantarjian et al., “Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia,” Cancer, vol. 115, no. 9, pp. 1899–1905, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  98. M. de Lima, L. D. P. Silva, S. Giralt et al., “Maintenance therapy with low-dose azacitidine (AZA) after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed AML or MDS: a dose and schedule finding study,” Blood, vol. 112, no. 11, 2008, abstract 1134. View at Google Scholar
  99. M. L. Sorror, M. B. Maris, B. Storer et al., “Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities,” Blood, vol. 104, no. 4, pp. 961–968, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus