Expert Insights into the Contemporary Management of Older Adults with Acute Myeloid Leukemia

Siegel R. , Naishadham D. , Jemal A. . CA Cancer J Clin. 2013; 63(1): 11–30.

Juliusson G. , Antunovic P. , Derolf A. . 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.

Alibhai S.M. , Leach M. , Minden M.D. . Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer. 2009; 115(13): 2903–2911.

Kantarjian H. , O'Brien S. . Questions regarding frontline therapy of acute myeloid leukemia. Cancer. 2010; 116(21): 4896–4901.

Thein M.S. , Ershler W.B. , Jemal A. . Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer. 2013; 119(15): 2720–2727.

Meyers J. , Yu Y. , Kaye J.A. . Medicare fee-for-service enrollees with primary acute myeloid leukemia: an analysis of treatment patterns, survival, and healthcare resource utilization and costs. Appl Health Econ Health Policy. 2013; 11(3): 275–286.

Tilly H. , Castaigne S. , Bordessoule D. . Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol. 1990; 8(2): 272–279.

Löwenberg B. , Zittoun R. , Kerkhofs H. . 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. J Clin Oncol. 1989; 7(9): 1268–1274.

Quintás-Cardama A. , Ravandi F. , Liu-Dumlao T. . Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood. 2012; 120(24): 4840–4845.

Sekeres M.A. , Elson P. , Kalaycio M.E. . Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood. 2009; 113(1): 28–36.

Patel J.P. , Gönen M. , Figueroa M.E. . Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012; 366(12): 1079–1089.

Kantarjian H. , O'Brien S. , Cortes J. . 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.

Krug U. , Röllig C. , Koschmieder A. . Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet. 2010; 376(9757): 2000–2008.

Röllig C. , Thiede C. , Gramatzki M. . A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood. 2010; 116(6): 971–978.

Appelbaum F.R. , Gundacker H. , Head D.R. . Age and acute myeloid leukemia. Blood. 2006; 107(9): 3481–3485.

Othus M. , Kantarjian H. , Petersdorf S. . Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson. Leukemia. 2013 Jun 13. Epub ahead of print.

Hurria A. , Cirrincione C.T. , Muss H.B. . Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011; 29(10): 1290–1296.

Extermann M. , Boler I. , Reich R.R. . Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012; 118(13): 3377–3386.

Wheatley K. , Brookes C.L. , Howman A.J. . Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRFAML14 trials. Br J Haematol. 2009; 145(5): 598–605.

Bross P.F. , Beitz J. , Chen G. . Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001; 7(6): 1490–1496.

Petersdorf S. , Kopecky K. , Stuart R.K. . Preliminary results of Southwest Oncology Group Study S0106: an International Intergroup Phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additional therapy for previously untreated acute myeloid leukemia. Blood (ASH Ann Meet Abstr). 2009; 114(22): 790. Abstract.

Castaigne S. , Pautas C. , Terré C. . Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012; 379(9825): 1508–1516.

Kantarjian H.M. , Erba H.P. , Claxton D. . Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol. 2010; 28(4): 549–555.

Pollyea D.A. , Zehnder J. , Coutre S. . Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica. 2013; 98(4): 591–596.

Pollyea D.A. , Kohrt H.E. , Gallegos L. . Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia. 2012; 26(5): 893–901.

Fehniger T.A. , Uy G.L. , Trinkaus K. . A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood. 2011; 117(6): 1828–1833.

Blum W.G. , Klisovic R. , Liu S. . Efficacy of a novel schedule of decitabine in previously untreated AML, age 60 or older. J Clin Oncol 2009 ASCO Ann Meet Proc (Post-Meet Ed). 2009; 27(15s May 20 suppl): 7010. Abstract.

Kantarjian H.M. , Thomas X.G. , Dmoszynska A. . Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012; 30(21): 2670–2677.

Fenaux P. , Mufti G.J. , Hellström-Lindberg E. . Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010; 28(4): 562–569.

van der Helm L.H. , Scheepers E.R. , Veeger N.J. . Azacitidine might be beneficial in a subgroup of older AML patients compared to intensive chemotherapy: a single centre retrospective study of 227 consecutive patients. J Hematol Oncol. 2013; 6(1): 29.

Cortes J.E. , Perl A.E. , Dombret H. . Final results of a phase 2 open-label, monotherapy efficacy and safety study of quizartinib (AC220) in patients ≥ 60 years of age with FLT3 ITD positive or negative relapsed/refractory acute myeloid leukemia. Blood (ASH Ann Meet Abstr). 2012; 120(21): 48. Abstract.

Ravandi F. , Alattar M.L. , Grunwald M.R. . Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013; 121(23): 4655–4662.

Lancet J.E. , Cortes J.E. , Kovacsovics T. . CPX-351 is effective in newly diagnosed older patients with AML and with multiple risk factors. Blood (ASH Ann Meet Abstr). 2012; 120(21): 3626. Abstract.

Roboz G.J. , Lancet J.E. , Cripe L.D. . Final results of a phase II pharmacokinetic/pharmacodynamic (PK/PD) study of combination voreloxin and cytarabine in patients with relapsed or refractory acute myeloid leukemia. J Clin Oncol. 2010 ASCO Ann Meet Proc (Post-Meet Ed). 2010; 28(15s May 20 suppl): 6526. Abstract.

Maertens J. , Lübbert M. , Fiedler W. . Phase I/II study of volasertib (BI 6727), an intravenous polo-like kinase (PLK) inhibitor, in patients with acute myeloid leukemia (AML): results from the randomized phase II part for volasertib in combination with low-dose cytarabine (LDAC) versus LDAC monotherapy in patients with previously untreated AML ineligible for intensive treatment. Blood (ASH Ann Meet Abstr). 2012; 120(21): 411. Abstract.

Bennett J.M. , Young M.L. , Andersen J.W. . Long-term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group experience. Cancer. 1997; 80(11 suppl): 2205–2209.

Löwenberg B. , Pabst T. , Vellenga E. . Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011; 364(11): 1027–1036.

Rowe J.M. , Kim H.T. , Cassileth P.A. . Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis: a report on 1980 patients registered to 6 studies conducted by the Eastern Cooperative Oncology Group. Cancer. 2010; 116(21): 5012–5021.

Burnett A.K. , Hills R.K. , Milligan D. . Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011; 29(4): 369–377.

Borthakur G. , Kantarjian H. , Wang X. . Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer. 2008; 113(11): 3181–3185.

Byrd J.C. , Mrózek K. , Dodge R.K. . Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002; 100(13): 4325–4336.

Löwenberg B. , Ossenkoppele G.J. , van Putten W. . High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009; 361(13): 1235–1248.

Burnett A. , Milligan D. , Prentice A. . 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.

Cashen A.F. , Schiller G.J. , O'Donnell M.R. . Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010; 28(4): 556–561.

Dombret H. , Gardin C. . An old AML drug revisited. N Engl J Med. 2009; 361(13): 1301–1303.

Faderl S. , Wetzler M. , Rizzieri D. . Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012; 30(20): 2492–2499.

Cortes J. , Feldman E. , Yee K. . Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study. Lancet Oncol. 2013; 14(4): 354–362.

Lancet J.E. , Ravandi F. , Ricklis R.M. . A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia. Leukemia. 2011; 25(12): 1808–1814.

Blum W. , Schwind S. , Tarighat S.S. . Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia. Blood. 2012; 119(25): 6025–6031.

Attar E.C. , Johnson J.L. , Amrein P.C. . Bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine for consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study 10502. J Clin Oncol. 2013; 31(7): 923–929.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Acute Myeloid Leukemia. Version 2.2013. http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed September 6, 2013.

Rogers B.B. . Advances in the management of acute myeloid leukemia in older adult patients. Oncol Nurs Forum. 2010; 37(3): E168–E179.

Higa G.M. , Gockerman J.P. , Hunt A.L. . The use of prophylactic eye drops during high-dose cytosine arabinoside. Cancer. 1991; 68: 1691–1693.

Jabbour E.J. , Estey E. , Kantarjian H.M. . Adult acute myeloid leukemia. Mayo Clin Proc. 2006; 81(2): 247–260.

Harris D.J. , Eilers J. , Harriman A. . Putting evidence into practice: evidence-based interventions for the management of oral mucositis. Clin J Oncol Nurs. 2008; 12(1): 141–152.