Challenges in treating older patients with acute myeloid leukemia

Lagadinou D Eleni, Zoumbos C Nicholas, Spyridonidis Alexandros, Lagadinou D Eleni, Zoumbos C Nicholas, Spyridonidis Alexandros

Abstract

Whereas in younger patients diagnosed with acute myeloid leukemia (AML) treatment is straightforward and the goal is cure, the optimal treatment decision for older adults remains highly controversial. Physicians need to determine whether palliation, "something" beyond palliation, intensive therapy, or an investigational therapy is the most appropriate treatment option. This requires understanding of the biology and risk profile of the AML, clinical judgment in evaluating the functional status of the patient, communication skills in understanding the patient's wishes and social background, and medical expertise in available therapies. The physician has to accurately inform the patient about (a) the unique biological considerations of his leukemia and his prognosis; (b) the risks and benefits of all available treatment options; (c) novel therapeutic approaches and how the patient can get access to these treatments. Last but not least, he has to recommend a treatment. This paper tries to discuss each of these issues.

References

    1. Sekeres MA, Stone RM, Zahrieh D, et al. Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia. 2004;18(4):809–816.
    1. Menzin J, Lang K, Earle CC, Kerney D, Mallick R. The outcomes and costs of acute myeloid leukemia among the elderly. Archives of Internal Medicine. 2002;162(14):1597–1603.
    1. Behringer B, Pitako JA, Kunzmann R, et al. Prognosis of older patients with acute myeloid leukemia receiving either induction or noncurative treatment: a single-center retrospective study. Annals of Hematology. 2003;82(7):381–389.
    1. Pulsoni A, Pagano L, Latagliata R, et al. Survival of elderly patients with acute myeloid leukemia. Haematologica. 2004;89(3):296–302.
    1. Estey EH. Treatment of acute myeloid leukemia. Haematologica. 2009;94(1):10–16.
    1. Hiddemann W, Kern W, Schoch C, et al. Management of acute myeloid leukemia in elderly patients. Journal of Clinical Oncology. 1999;17(11):3569–3576.
    1. Klepin HD, Balducci L. Acute myelogenous leukemia in older adults. Oncologist. 2009;14(3):222–232.
    1. Leith CP, Kopecky KJ, Godwin J, 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. 1997;89(9):3323–3329.
    1. Fialkow PJ, Singer JW, Raskind WH. Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia. The New England Journal of Medicine. 1987;317(8):468–473.
    1. Wilson CS, Davidson GS, Martin SB, et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood. 2006;108(2):685–696.
    1. Ferrara F, Pinto A. Acute myeloid leukemia in the elderly: current therapeutic results and perspectives for clinical research. Reviews on Recent Clinical Trials. 2007;2(1):33–41.
    1. Cheson BD, Jasperse DM, Simon R, Friedman MA. A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes. Journal of Clinical Oncology. 1986;4(12):1857–1864.
    1. Burnett AK, Milligan D, Prentice AG, 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. 2007;109(6):1114–1124.
    1. Wahlin A, Hornsten P, Jonsson H. Remission rate and survival in acute myeloid leukemia: impact of selection and chemotherapy. European Journal of Haematology. 1991;46(4):240–247.
    1. Fröhling S, Schlenk RF, Kayser S, 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. 2006;108(10):3280–3288.
    1. Prebet T, Boissel N, Reutenauer S, 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. 2009;27(28):4747–4753.
    1. Breems DA, Van Putten WLJ, de Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. Journal of Clinical Oncology. 2008;26(29):4791–4797.
    1. O’Donnell MR, Appelbaum FR, Baer MR, et al. Acute myeloid leukemia: clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network. 2006;4(1):16–36.
    1. Morra E, Barosi G, Bosi A, 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. 2009;94(1):102–112.
    1. Grimwade D, Walker H, Harrison G, 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. 2001;98(5):1312–1320.
    1. Gupta V, Chun K, Yi Q-L, 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. 2005;103(10):2082–2090.
    1. Buchner T, Berdel WE, Haferlach C, 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. 2009;27(1):61–69.
    1. Schlenk RF, Döhner K, Kneba M, 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. 2009;94(1):54–60.
    1. Sekeres MA, Elson P, Kalaycio ME, et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood. 2009;113(1):28–36.
    1. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107(9):3481–3485.
    1. Kantarjian H, O’Brisn S, Cortes J, 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. 2006;106(5):1090–1098.
    1. Malfuson J-V, Etienne A, Turlure P, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica. 2008;93(12):1806–1813.
    1. Lowenberg B, Zittoun R, Kerkhofs H, 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. 1989;7(9):1268–1274.
    1. Juliusson G, Antunovic P, Derolf Å, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009;113(18):4179–4187.
    1. Büchner T, Hiddemann W, Berdel W, et al. Acute myeloid leukemia: treatment over 60. Reviews in Clinical and Experimental Hematology. 2002;6(1):46–59.
    1. Rees JKH, Gray RG, Wheatley K. 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. 1996;94(1):89–98.
    1. Lowenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. The New England Journal of Medicine. 2009;361(13):1235–1248.
    1. Weick JK, Kopecky KJ, Appelbaum FR, 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. 1996;88(8):2841–2851.
    1. Buchner T, Hiddemann W, Berdel WE, 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. 2003;21(24):4496–4504.
    1. Schiller G, Lee M. Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for older patients with acute myelogenous leukemia. Leukemia and Lymphoma. 1997;25(1-2):111–119.
    1. Reiffers J, Huguet F, Stoppa A-M, 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. 1996;10(3):389–395.
    1. Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood. 2005;106(4):1154–1163.
    1. Miyauchi J, Kelleher CA, Wang C, Minkin S, McCulloch EA. Growth factors influence the sensitivity of leukemic stem cells to cytosine arabinoside in culture. Blood. 1989;73(5):1272–1278.
    1. Amadori S, Suciu S, Jehn U, 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. 2005;106(1):27–34.
    1. Dombret H, Chastang C, Fenaux P, 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. 1995;332(25):1678–1683.
    1. Milligan DW, Wheatley K, Littlewood T, Craig JIO, Burnett AK. 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. 2006;107(12):4614–4622.
    1. Wheatley K, Goldstone AH, Littlewood T, Hunter A, Burnett AK. 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. 2009;146(1):54–63.
    1. Nervi B, Ramirez P, Rettig MP, et al. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood. 2009;113(24):6206–6214.
    1. Uy GL, Rettig MP, Mcfarland KM. 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. 2008;112(11) abstract 1944.
    1. Matsouka P, Pagoni M, Zikos P, 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. 2006;85(4):250–256.
    1. List AF, Kopecky KJ, Willman CL, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2001;98(12):3212–3220.
    1. Greenberg PL, Lee SJ, Advani R, 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. 2004;22(6):1078–1086.
    1. Erba HP. Prognostic factors in elderly patients with AML and the implications for treatment. Hematology. 2007:420–428.
    1. Burnett AK, Milligan D, Goldstone A, 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. 2009;145(3):318–332.
    1. Cripe LD, Li X, Litzow M, 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. 2006;108, article 129a
    1. Burnett AK, Baccarani M, Johnson P, Yin J, Russell N. Clofarabine in previously untreated elderly (>65 yrs) AML patients with an unfavourable cytogenetic profile who are considered unfit for standard intensive chemotherapy. Blood. 2006;24(18S) abstract 6513.
    1. Erba HP, Kantarjian HM, Claxton D, 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. 2008;(20S) abstract 7025.
    1. Faderl S, Ravandi F, Huang X, 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. 2008;112(5):1638–1645.
    1. Karp JE, Rizzieri D, Vey N, et al. Cloretazine is an effective induction therapy in elderly patients (pts) with poor-risk de novo AML. Journal of Clinical Oncology. 2006;24(18S)
    1. Karp JE, Rizzieri D, Vey N, et al. Cloretazine is an effective induction therapy in elderly patients (pts) with poor-risk de novo AML. Journal of Clinical Oncology. 2006;24(18S)
    1. Daskalakis M, Nguyen TT, Nguyen C, et al. Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-aza-2′-deoxycytidine (decitabine) treatment. Blood. 2002;100(8):2957–2964.
    1. Kaminskas E, Farrell A, Abraham S, et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clinical Cancer Research. 2005;11(10):3604–3608.
    1. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, 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. 2009;10(3):223–232.
    1. Fenaux P, Mufti GJ, Hellström-Lindberg E, 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. 2008;112 abstract 3636.
    1. Ravandi F, Issa J-P, Garcia-Manero G, 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. 2009;115(24):5746–5751.
    1. Lubbert M, Ruter B, Claus R, 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. 2007;110(95a) abstract 300.
    1. Larson RA, Sievers EL, Stadtmauer EA, 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. 2005;104(7):1442–1452.
    1. Doyen J, Italiano A, Peyrade F, Bouyer C, Thyss A. Gemtuzumab ozogamicin plus cytarabine in elderly patients with relapsed or refractory acute myeloid leukaemia. British Journal of Haematology. 2008;141(5):744–745.
    1. Fianchi L, Pagano L, Leoni F, 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. 2008;19(1):128–134.
    1. Amadori S, Suciu S, Willemze R, 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. 2004;89(8):950–956.
    1. Clavio M, Vignolo L, Albarello A, 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. 2007;138(2):186–195.
    1. Nand S, Godwin J, Smith S, 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. 2008;49(11):2141–2147.
    1. Harousseau J-L, Martinelli G, Jedrzejczak WW, 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. 2009;114(6):1166–1173.
    1. Knapper S, Burnett AK, Littlewood T, 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. 2006;108(10):3262–3270.
    1. Deeg HJ, Shulman HM, Anderson JE, et al. Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood. 2000;95(4):1188–1194.
    1. Du W, Dansey R, Abella EM, et al. Successful allogeneic bone marrow transplantation in selected patients over 50 years of age—a single institution’s experience. Bone Marrow Transplantation. 1998;21(10):1043–1047.
    1. Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. Journal of Clinical Oncology. 2003;21(8):1480–1484.
    1. Estey E, de Lima M, Tibes R, 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. 2007;109(4):1395–1400.
    1. Finke J, Nagler A. 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. 2007;21(7):1357–1362.
    1. Hegenbart U, Niederwieser D, Sandmaier BM, 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. 2006;24(3):444–453.
    1. Ho AYL, Pagliuca A, Kenyon M, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood. 2004;104(6):1616–1623.
    1. Kroger N, Bornhäuser 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. Annals of Hematology. 2003;82(6):336–342.
    1. Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003;102(6):2021–2030.
    1. Marks R, Potthoff K, Hahn J, et al. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008;112(2):415–425.
    1. Mohty M, de Lavallade H, El-Cheikh J, 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. 2009;23(1):194–196.
    1. Ringden O, Labopin M, Ehninger G, et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. Journal of Clinical Oncology. 2009;27(27):4570–4577.
    1. Shimoni A, Kröger N, Zabelina T, 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. 2005;19(1):7–12.
    1. 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(3):756–763.
    1. Spyridonidis A, Bertz H, Ihorst G, Grüllich C, Finke J. Hematopoietic cell transplantation from unrelated donors as an effective therapy for older patients (≥60 years) with active myeloid malignancies. Blood. 2005;105(10):4147–4148.
    1. Wong R, Giralt SA, Martin T, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood. 2003;102(8):3052–3059.
    1. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb H-J. 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. 2005;23(24):5675–5687.
    1. Russell NH, Byrne JI, Robinson SP. Defining conditioning regimens for BMT-recognition of “regimens of intermediate intensity”. Biology of Blood and Marrow Transplantation. 2009;15(7):890–891.
    1. de Lima M, Anagnostopoulos A, Munsell M, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood. 2004;104(3):865–872.
    1. 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(2):322–328.
    1. de Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104(3):857–864.
    1. 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(2):725–731.
    1. Petersen FB, Ford CD. Maximum supportive care, standard conditioning and allogeneic stem cell transplantation for elderly patients with acute myelogenous leukemia. Current Opinion in Oncology. 2009;21(supplement 1):S7–S9.
    1. Flowers MED, Traina F, Storer B, et al. Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning. Bone Marrow Transplantation. 2005;35(3):277–282.
    1. Schetelig J, Bornhäuser M, Schmid C, 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. 2008;26(32):5183–5191.
    1. Sayer HG, Kröger M, Beyer J, 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. 2003;31(12):1089–1095.
    1. Anderson JE, Gooley TA, Schoch G, et al. Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy. Blood. 1997;89(7):2578–2585.
    1. Jabbour E, Giralt S, Kantarjian H, et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer. 2009;115(9):1899–1905.
    1. de Lima M, Silva LDP, Giralt S, 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. 2008;112(11) abstract 1134.
    1. 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(4):961–968.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi