Hematology in Aging

Published on 04/03/2015 by admin

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Chapter 73 Hematology in Aging

Andrew S. Artz, William B. Ershler

Table 73-1 Anemia Definitions

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Adapted from Beutler E, Waalen J: The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 107:1747, 2006.

Table 73-2 Hematopoietic Changes Associated With Advancing Age

Diminished bone marrow cellularity

Reduced CD34+ cell mobilization to G-CSF administration in healthy donors

Decreased stem cell telomeres

Reduced hematopoietic cell proliferative capacity

Increased numbers of hematopoietic stem cells

Reduction in lymphocyte function

Reduced response to vaccination

Development of unexplained anemia*

G-CSF, Granulocyte colony-stimulating factor.

*Guralnik JM, Eisenstaedt RS, Ferrucci L, et al: Prevalence of anemia in persons 65 years and older in the United States: Evidence for a high rate of unexplained anemia. Blood 104:2263, 2004.

Evaluating Anemia in Older Adults

Anemia in older adults is a common finding and frequently results in a request for hematology consultation.

To define anemia, we follow the hemoglobin criteria defined by Beutler and Waalen in Table 73-1. However, hemoglobin trajectory over time is as important. Based on the fact that the average hemoglobin level declines in older adults about 1 g/dL over 15 years or more, we consider decline of 1 g/dL in less than 5 years or 2 g/dL over 10 years significant and supports a complete evaluation. We work diligently to retrieve remote blood counts. Older adults frequently have had blood counts obtained either routinely in the past, before a procedure, or at the time of hospital admission. Counts at the time of hospital admission may be the least reliable because they occur in the context of an illness.

To elicit symptoms, both the patient and family members or caregivers who know the patient are asked about functional changes (walking, naps, activity level) over the short-term (weeks) and longer term (months to years). Many older adults will often attribute functional changes to “old age.”

Our basic evaluation begins with a complete blood count, red cell indices, and review of the peripheral smear. The red cell size by mean corpuscular volume is helpful but imperfect. We also perform a reticulocyte count, but 95% or more of anemias in older adults are hypoproliferative. Because anemia can be mixed or multifactorial, we routinely perform the same panel on most patients: serum ferritin, serum iron, total iron-binding capacity, serum creatinine (and estimated renal function), vitamin B12, and thyrotropin levels. We also have found c-reactive protein and serum erythropoietin to be very useful. High c-reactive protein level, such as above 10 mg/L, is frequently associated with inflammatory illnesses and raises caution in interpreting the serum ferritin level. Serum erythropoietin levels are typically in the reference range (i.e., inappropriately low) for most older anemic adults except for iron deficiency, hematologic malignancy, or hyperproductive anemias. Folate levels are rarely low, at least in the United States, where dietary folate supplementation is universal. The remainder of the laboratory tests will be performed as indicated. We do not routinely evaluate for a serum monoclonal gammopathy unless unexplained renal dysfunction, elevated total protein level, elevated calcium level, or bone pain is present.

A ferritin level of less than 50 ng/mL will prompt a complete evaluation for iron deficiency. At a minimum, we embark on an oral iron trial and fecal tests for blood. The lower the iron stores and more evidence for iron deficiency anemia, the more we recommend endoscopic gastrointestinal evaluation, assuming no other cause is clearly established. Other measures exist for diagnosing iron deficiency, such as reticulocyte counts, serum transferrin receptor, or intravenous iron trials. We also empirically treat if vitamin B12 levels are less than 200 pg/mL with oral vitamin B12 at 1000 mcg for 8 to 12 weeks. If there is no response, we discontinue therapy.

A bone marrow examination is recommended if any of the following are present: unexplained requirement for red blood cell transfusion therapy, unexplained mean corpuscular volume of 97 fL or greater, thrombocytopenia below 120 × 109/L, neutropenia below 1000 × 109/L, or suspicious peripheral smear. If the bone marrow is nondiagnostic, we only repeat the marrow examination at the time of clinical progression (e.g., red blood cell transfusion required, the development of more significant cytopenias).

When the anemia has no established cause, the hemoglobin level is above 10 g/dL, the patient lacks major symptoms, and the hemoglobin kinetics are stable (i.e., fall of less than 1 g/dL over 5 years), we follow up with blood cell counts every 6 months and then annually. Any significant fall in hemoglobin will prompt repeat evaluation. We do not routinely administer erythropoiesis-stimulating agents for unexplained anemia.

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Figure 73-1 CATEGORIZATION OF PRIMARY ANEMIA ETIOLOGY OR UNEXPLAINED ANEMIA IN THE ELDERLY (UAE) IS SHOWN.

IDA, Iron deficiency anemia; ACI, anemia of chronic inflammation; Heme malig, hematologic malignancy; CKD, chronic kidney disease; Thal, thalassemia trait; Oth, other. (Other includes hemolysis, 4; alcohol, 3; hypothyroidism, 1; vitamin B12 deficiency, 1; medication, 1.)

(From Artz AS, Thirman MF: Unexplained anemia predominates despite an intensive evaluation in a racially diverse cohort of older adults from a referral anemia clinic. J Gerontol A Biol Sci Med Sci 66:925, 2011.)

Table 73-3 Differential Diagnosis for Common Causes of Cytopenias in Older Adults

Cytopenia of one or more lineages

Hematologic neoplasm

Vitamin B12 deficiency

Autoimmune disorder

Consumptive coagulopathy

Systemic inflammation

Alcohol

Splenomegaly

Thyroid dysfunction

Human immunodeficiency virus

Assessment of Older Adults With Hematologic Malignancies

Optimal treatment for a hematologic condition in an older patient must be measured in terms of both efficacy and anticipated toxicity. Assessing patients’ reserve before treatment not only promotes tailoring treatment, but also provides an objective baseline assessment and an opportunity to direct interventions for these limitations.

For all adults over 50 years, we screen for age-associated vulnerabilities. Cataloging comorbid conditions and assessing performance status (PS) play a central role. Estimating PS alone provides only a crude estimate of tolerance to treatment. An Eastern Cooperative Oncology Group (ECOG) PS of 2 or more suggests important health limitations, but one must recognize that a PS of 0 to 1 covers a broad range of health, from robust to substantial limitations. In older patients, it is important to estimate PS before the current illness, because this is more likely to provide insight into vulnerability. We find insufficient data to recommend a specific comorbidity tool or index. However, certain tools such as the Charlson comorbidity index or hematopoietic cell transplantation–comorbidity index have been validated in the context of certain diseases and their treatments and thus may be invaluable in specific situations.

The PS and comorbidity index should be complemented by screening for other vulnerabilities, particularly in those older patients with a PS of 0 to 2 for whom intensive therapy is under consideration. Limitations in the following domains also suggest vulnerability:

• Instrumental activities of daily living, which are the skills required to live independently in the community (e.g., transportation, paying bills, shopping)

• Poor caregiver support

• Cognition

• Age 70 years and older

One should not overlook inquiring specifically about whether patients perceive problems for the recommended treatment. Patients will often relay difficulties not recognized by a standard medical examination (e.g., caring for an ill-spouse, limited prescription coverage, and poor perceived health). More formal screening instruments are available and useful if familiarity can be achieved (e.g., Vulnerable Elders Survey-13).

Knowledge of disease-based response rates will allow further individualizing treatment decisions. Responses to imatinib for chronic-phase chronic myeloid leukemia do not differ substantially by age, whereas acute myeloid leukemia induction results in lower responses, shorter disease-free survival, and greater toxicity relative to younger adults, even among relatively “young” healthy adults in their seventh decade of life.

Although disease-based therapy exists on a spectrum, we generally divide therapy into low-intensity, intermediate-intensity, or high-intensity therapy. High-intensity treatment entails strategies such as AML induction and autologous or allogeneic hematopoietic cell transplantation, and these have high rates of early death for patients with health limitations. Prior treatment and disease status influence the expected complication rate. Refractory or relapsed disease or multiple prior regimens may escalate the expected complications and may warrant providing traditionally less-intensive therapy instead of high-intensity treatment strategies. We typically reserve high-intensity therapy for patients with a preserved PS. We recommend that a patient with any vulnerability on screening undergo a more comprehensive geriatric assessment, if available, before curative-intent intensive therapy. Clinics focusing on issues and research in geriatric oncology are becoming available, and identifying experts (physician and nonphysician) in aging with an interest in oncology is invaluable. They often can connect patients with resources for specific problems (e.g., home care, transportation, financial help, assisted living).

Intermediate-intensity therapy such as CHOP (cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone)-like regimens and fludarabine plus cyclophosphamide may be somewhat more likely to produce manageable toxicity-related morbidity in older patients, but they remain efficacious and can be administered safely to those with a PS of 2 or better. Demethylating agents span the gap between low- and intermediate-intensity therapy. Low-intensity therapies, such as imatinib or supportive care alone, generally require only a reasonable nondisease life expectancy of more than a couple of months and can be given with an ECOG PS of 3 or less.

Patient support often extends past the traditional nuclear family and may include friends, business associates, or extended relatives. We strongly encourage a family meeting before initiating treatment at which goals and expectations are clearly discussed. Not only will insights be gained into the available support system, but communicating to the entire team harmonizes goals for providers and patients alike. Supportive care should be addressed prospectively before treatment plans and with the entire “treatment family.” Standard guidelines for infectious disease prophylaxis and growth factor support should be supplemented with plans to address limitations found in the initial assessment.

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