The last 3 decades have demonstrated improvements in AML (acute myeloid leukemia) mostly in those under the age of 65 years.1 This unfortunately is not the case in elderly patients who represent the majority of patients diagnosed with this malignancy. With the median age of diagnosis being 67, most older patients with AML fare significantly worse than their younger counterparts. Consider the following:
- Ten percent to 20% of the elderly die of complications during induction chemotherapy;
- Forty-five percent to 65% achieve complete remissions;
- Seventy percent will die of AML within 1 year following diagnosis;
- No more than 15% of those in remission will survive long term.2-4
These statistics are troublesome for several reasons. First, is that individuals aged 65 in the western world have a life expectancy of an additional 20 years. Hence, the elderly with AML are not living to this projected lifespan. Second, is that with the graying of developed countries, the relative number and percentage of elderly is expected to rise exponentially. This will result in considerable increases in the majority of adult malignancies characterized by advanced age being a major risk factor.5, 6 Thus, the optimum treatment of AML in older adults represents a major problem now and most certainly in the future.
AML emanates from abnormal proliferation and differentiation of clonal populations of myeloid stem cells. An accumulation of these stem cells in the bone marrow and peripheral blood result in leukocytosis and bone marrow failure with clinical manifestations at initial presentation of anemia, thrombocytopenia, fatigue, anorexia, and weight loss. The elderly also have evidence of an adverse cytogenetic profile such as chromosomal translocations and genetic mutations.2 Additionally, they demonstrate expression of multidrug resistance proteins.3 These poor-risk cytogenetics, along with advanced age, poor performance status, and history of prior myelodysplasia, combine to characterize patients with a poor prognosis or heightened likelihood of treatment-related mortality.
Other prognostic factors include the presence of comorbidity and polypharmacy, and cognitive status.4 The elderly, like other developmental subsets, are a heterogeneous group. Hence, chronological age alone is not predictive of treatment tolerability or therapeutic outcome. Rather physiologic age should be the primary consideration as should other factors.
Almeida and Ramos4 identified four main factors that should guide treatment planning: the patientís clinical condition, disease characteristics, patient wishes, and social support. These take into account the important variables of the presence of comorbidity and related polypharmacy, cytogenetic profile, individual decision-making preferences, and the availability of family support to assist with needs related to dependency such as basic activities, transportation, meals, monitoring, and medication adherence.
Only 40% of elderly patients with AML receive treatment within 3 months of diagnosis.7 It is unclear whether this is due to patient factors precluding therapy, patient/family preferences, or provider bias. Regardless, optimum therapies for the elderly with AML have not been established.2
Standard therapy (i.e., ď3+7Ē followed by two to three courses of consolidation with high-dose cytarabine) is often inappropriate and unsuccessful in elderly patients.4 This regimenís demands on hematologic and immune function, as well as major organs, makes its tolerability minimal in most older adults. The same is true of allogeneic hematopoietic cell transplantation (HCT) where only 17% of recipients are between the ages of 60 and 80 years.8
The hypomethylating agent azacitidine (Vidaza) is currently the most common therapy given to older adults newly diagnosed with AML.9 Additionally, the drug clofaradine (Clolar), a second generation purine nucleoside analog that has been approved for relapsed or refractory acute lymphocytic leukemia in children, is well tolerated when added to low-dose cytarabine in the elderly unable to tolerate standards therapy.2 Novel agents likely to become available in the future include monoclonal antibody-directed therapies and the immune-modulating and antiangiogenic agent lenalidomide (Revlimid) in high doses.3
Currently, while success in treating AML in the elder majority is marginal at best, evolving laboratory and clinical research will hopefully change the future treatment landscape for older adults. This represents only one element of the geriatric oncology paradigm that requires pressing attention.
- Burnett AK. Treatment of acute myeloid leukemia: Are we making progress? Am Soc Hematol Educ Program. 2012;2012:1-6.
- De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: A comprehensive review and 2016 update. Blood Cancer J. 2016 Jul 1;6(7):e441.
- Amadori S, Del Principe MI, Venditti A. Advances in the treatment of elderly and frail patients with acute myeloid leukemia. Curr Opin Oncol. 2014 Nov;26(6):663-9.
- Almeida AM, Ramos F. Acute myeloid leukemia in the older adult. Leukemia Res Reports. 2016; 6: 1-7.
- Edwards BK, Howe H, Ries L, et al. Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden. Cancer. 2002 May 15;94(10):2766-92.
- Hurria A, Naylor M, Cohen HJ. Improving the quality of cancer care in an aging population: Recommendations from an IOM report. JAMA. 2013 Nov 6;310(17):1795-6.
- Medeiros BC, Satram-Hoang S, Hurst D, et al. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015 Jul;94(7):1127-38.
- Sorror ML, Estey E. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults. Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):21-33.
- Estey E. Acute myeloid leukemia: 2016 update on risk-stratification and management. Am J Hematol. 2016 Aug;91(8):824-46.