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Acute myeloid leukemia (AML) is a disease of the elderly, but less than half of these patients are offered therapy despite the evidence of better survival with treatment in this patient population. Assessing fit, vulnerable, and frail older adults with AML remains a challenge for the treating oncologist. A majority of AML patients are elderly and often have significant comorbidities, lack of social support, and older caregivers. Performance status (PS), a subjective measure of how a patient will tolerate cancer chemotherapy, has been strongly correlated with mortality in older AML patients. However, a large portion of older adults have poor PS as a result of their underlying AML, and these patients may end up being undertreated. Conversely, some patients with excellent PS unexpectedly end up with excessive toxicity and mortality. The treating physician thus needs a more objective and comprehensive method to differentiate patients along the fit-frail spectrum irrespective of their chronological age. For more than a decade, comprehensive geriatric assessment has been shown to improve routine oncology assessment by adding information about the functional, emotional, cognitive, and social status of older patients with cancer. In addition to the chronological and functional age, there is an attempt to quantify a patient's biological age to aid in better decision making. This chapter attempts to review the clinical challenges of AML treatment in the elderly population and to highlight the current literature and future research required to be able to assess fitness and maximize therapeutic options in this heterogeneous patient population., (© 2016 by The American Society of Hematology. All rights reserved.)

Acute myeloid leukemia (AML) accounts for approximately 80% of acute leukemias diagnosed in adults. The elderly are disproportionately affected by AML, as 35% of newly diagnosed patients are aged >or=75 and the median age at diagnosis is 67. Elderly individuals also respond less well to standard chemotherapy than do younger individuals, as reflected by lower complete remission and relapse-free survival rates in major clinical trials. A higher prevalence of comorbid conditions as well as the unique biological features of elderly AML patients account for the relatively poor response to therapy observed in this population. Compared with AML in younger individuals, for example, AML in the elderly more often emerges from a preceding myelodysplastic syndrome and is more frequently associated with poor-prognosis karyotypes such as 5q- or 7q-. The introduction of novel therapies over the past decade has already altered the treatment paradigm of elderly individuals with AML. The first of these to emerge was gemtuzumab ozogamicin. Other agents are currently under evaluation in clinical trials, including inhibitors of multidrug resistance, farnesyltransferase inhibitors, novel nucleoside analogues, and inhibitors of the FMS-like tyrosine kinase-3. This review describes the biological features of AML in the elderly and summarizes both the current and emerging strategies for the treatment of this disease in older individuals.

Background: Biological agents are proving to be increasingly useful and exciting additions to the antineoplastic armamentarium, but many clinicians are unfamiliar with the properties of these types of agents., Objectives: This review focuses on monoclonal antibodies (MAbs) that are used in the treatment of hematologic malignancies. Our goal was to provide the reader with information on trials that led to US Food and Drug Administration (FDA) approval of commonly used MAbs in hematologic malignancies, including their mechanisms of action and pharmacokinetics, with specific emphasis on use in elderly patients; we also present data on toxicities and precautions to be aware of when administering these drugs., Methods: Materials for this review were gathered based on a computerized literature search (English-language articles only) using the PubMed database covering the period January 1998 to December 2005. Search terms used included the following: elderly, monoclonal antibodies, and neoplasms., Results: Alemtuzumab is a recombinant DNA-derived, humanized MAb directed against the CD52 B-cell antigen. It is indicated for the treatment of B-cell chronic lymphocytic leukemia (CLL) in patients who have been treated with alkylating agents and who have failed to respond to fludarabine therapy. Gemtuzumab ozogamicin is an MAb conjugated with a cytotoxic antitumor antibiotic, calicheamicin. It has been approved for use in patients with CD33-positive acute myeloid leukemia (AML) in first relapse who are aged > or =60 years and who are not considered candidates for other cytotoxic chemotherapy. Rituximab, one of the first MAbs approved by the FDA for use in human cancers, is an antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. It is extensively used in the treatment of B-cell malignancies, such as CLL, and non-Hodgkin's lymphomas (NHLs), such as follicular lymphoma and diffuse large B-cell lymphoma., Conclusions: It is noteworthy that while there have been a number of studies using these agents in the younger population, there continues to be a paucity of clinical trials targeting the elderly patient in particular; this continues to be an area of research interest. More clinical studies of these agents--conducted specifically in elderly patients with CLL, NHL, AML, and other hematologic malignancies--are needed.