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Hematological Malignancies Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma Loretta J Nastoupil, MD, 1 Rajni Sinha, MD 2 and Christopher R Flowers, MD, MS 3 1. Fellow; 2. Assistant Professor; 3. Director, Lymphoma Program and Associate Professor, Department of Hematology and Oncology, Winship Cancer Institute Abstract Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the aging population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more comorbid illnesses, worse performance status, less hematologic reserve, and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated. Keywords Diffuse large B-cell lymphoma, non-Hodgkin lymphoma, elderly, treatment, cancer, lymphoma, age, therapy Disclosure: Loretta J Nastoupil, MD, has no conflicts of interest to declare. Rajni Sinha, MD, has received research funding from Celgene. Christopher R Flowers, MD, MS, has received consultancy fees from Spectrum, Celgene, and Seattle Genetics, has undertaken unpaid consultancy for Millennium/Takeda and Genentech/Roche, and has received research funding from Spectrum, Millenium Takeda, Celgene, and Novartis. Received: February 3, 2012 Accepted: February 14, 2012 Citation: Oncology & Hematology Review, 2012;8(1):71–5 Correspondence: Christopher R Flowers, MD, MS, Department of Hematology and Oncology, Winship Cancer Institute, 1365 Clifton Road, N.E. Building B, Suite 4302, Emory University Atlanta, GA 30322. E: crflowe@emory.edu Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non-Hodgkin lymphoma (NHL), accounting for approximately one-third of adult lymphomas. There was an unprecedented rise in NHL incidence (3–4 % per year) from the 1970s to the mid-1990s, comparable only to the rise in skin cancers. 1 It is estimated that there will be 70,140 new NHL cases in 2012, making NHL the seventh most common cancer. 2 DLBCL most commonly presents in the sixth decade, but there is some racial variation in the age of onset, with white Americans presenting at a mean age of 64 compared with a mean age of 54 for black patients. 3 Although there appears to be a stabilization in the incidence of lymphoma since the late 1990s in young patients, this does not appear to be true for elderly patients, the majority of whom present over the age of 65. 4,5 The median age of the world’s population is increasing, with the proportion of the US population aged ≥65 years projected to increase from 12.4  % in 2000 to 19.6  % in 2030. 6 It is expected that the prevalence of NHL will increase with the aging population, and it is well recognized that this patient population would benefit from the most appropriate modern therapy. © TOUCH BRIEFINGS 2012 Although heterogeneous, DLBCL has an aggressive natural history, with a median survival of one year in untreated patients. 7 In the majority of studies conducted before 2000, older patients were systematically considered to be poor candidates for standard therapy and were treated with less intensive regimens. 8,9 The dilemma when managing elderly patients is that, with aggressive treatment, DLBCL is curable in the majority of patients; however, providing adequate therapy to this patient population can be complicated by comorbid conditions, decreased drug metabolism, and worse performance status when compared with younger patients. Herein, we examine emerging trends in the clinical management and biology of DLBCL in the elderly patient population, and explore findings from recent meetings and publications that will aid in further defining our management of this disease. Age, Clinical, or Biologic Predictor Age has been one of the most important adverse prognostic features in NHL. Numerous studies have associated older age with inferior outcomes. 10–13 Age, stratified at >60 years, is a component of the international prognostic index (IPI), developed in the 1990s as a clinical 71