Introduction to a review series on hematologic disease at older age

The incidence of hematologic disease progressively increases with age. This is true for almost all of the hematologic malignancies as well as a variety of benign hematologic disorders. Hematologic conditions in the elderly pose specific challenges with regard to not only their diagnosis but also their treatment options. The biology of “healthy” aging is associated with numerous and widely diverse alterations in cellular function and typically may be coupled to a loss of organ function. The alterations induced or accelerated by external factors set the stage for the development of diseases with distinct genotypes and characteristic phenotypes. Emerging insights into the underlying biology have uncovered novel mechanisms of “hematologic” aging and disclosed the complexity of the pathogenetic pathways and molecular features of these disorders. Hematologic disease at older age frequently also requires a specific, adjusted therapeutic approach. In addition, the context of the reduced functional vitality of the nonhematopoietic organs (lung, heart, kidney) may have implications for how older subjects with hematologic disease will respond to treatment. Altogether, the subject of hematologic disease in the elderly has become a subject of broad scientific and considerable clinical significance.

The series of reviews published in this issue of Blood and written by leaders in the field highlight biologic and clinical concepts related to hematologic disease associated with aging. The first 3 reviews examine our current knowledge of the biology of aging. The fourth and fifth reviews discuss aspects of the diagnostic and therapeutic management of older patients with hematologic disease as they commonly present in clinical practice.

1. “Aging of hematopoietic stem cells” by Gerald de Haan and Seka Simone Lazare. Hematopoietic stem cells ensure a balanced production of all blood cells, and loss of regenerative abilities impacts severe dysfunction. In the first review, the authors discuss how particular molecular mechanisms contribute to stem cell aging challenging an individual’s health.

2. “DNA damage responses and p53 in the aging process” by Hui-Ling Ou and Björn Schumacher. In their comprehensive overview, the authors highlight the substantial impact of genotoxic insults on the genome during aging and the profound role of accumulating DNA damage on age-associated biologic alterations in the development of disease.

3. “Age-related clonal hematopoiesis” by Liran I. Shlush. The continued reduction of the genetic diversity of the hematopoietic stem cell pool that is seen with progressive age affects the health of the aging individual and colors the biology of a variety of diseases, both hematopoietic and nonhematopoietic, in the elderly. The author examines the clinical impact of “age-related clonal hematopoiesis.” Age-related clonal expansions in the human hematopoietic stem cell pool characterized by specific genetic variants become evident in individuals with no or not yet apparent hematologic disease.

4. “Anemia at older age: etiologies, clinical implications, and management” by Reinhard Stauder, Peter Valent, and Igor Theurl. In the fourth article, the authors review current concepts and the clinical challenges of anemia, a highly common disorder in people of older age.

5. “Frailty and the management of hematologic malignancies” by Gregory A. Abel and Heidi D. Klepin. In the last article of this series of reviews, Abel and Klepin define “frailty” as a “vulnerable state that arises from decreased reserve in multiple organ systems, which are initiated by disease, lack of activity, inadequate nutritional intake, stress, and/or the physiologic changes of aging.” They highlight the importance of recognizing frailty for the clinical management of patients of older age with hematologic disease, and they identify issues relevant to our daily clinical practice.