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Am Fam Physician. 2023;107(4):397-405

Patient information: See related handout on leukemia.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Leukemia is caused by an abnormal proliferation of hematopoietic stem cells in the bone marrow. The four general subtypes are acute lymphoblastic, acute myelogenous, chronic lymphocytic, and chronic myelogenous. Acute lymphoblastic leukemia primarily occurs in children, whereas the other subtypes are more common in adults. Risk factors include certain chemical and ionizing radiation exposures and genetic disorders. Common symptoms include fever, fatigue, weight loss, joint pain, and easy bruising or bleeding. Diagnosis is confirmed with bone marrow biopsy or peripheral blood smear. Hematology-oncology referral is recommended in patients with suspected leukemia. Chemotherapy, radiation, targeted molecular therapy, monoclonal antibodies, or hematopoietic stem cell transplantation are common treatments. Complications from treatment include serious infections from immunosuppression, tumor lysis syndrome, cardiovascular events, and hepatotoxicity. Long-term sequelae in leukemia survivors include secondary malignancies, cardiovascular disease, and musculoskeletal and endocrine disorders. Five-year survival rates are highest in younger patients and those diagnosed with chronic myelogenous or chronic lymphocytic leukemia.

Leukemia is one of the most common malignancies in childhood, but it also often occurs in adults. It is caused by disruptions in the normal cell regulatory process that leads to uncontrolled proliferation of hematopoietic stem cells in bone marrow. From 2015 to 2019, the age-adjusted incidence of leukemia in the United States was 14.1 per 100,000 people per year.1 In the past decade, the incidence of leukemia has been decreasing while survival rates have been increasing due to advancements in diagnosis and treatment.1 The four general leukemia subtypes are acute lymphoblastic, acute myelogenous, chronic lymphocytic, and chronic myelogenous. Primary care physicians should be familiar with common presentations, initial diagnostic evaluation, principles of therapy, and long-term sequelae in survivors.

RecommendationSponsoring organization
Do not perform baseline or routine surveillance computed tomography in patients with asymptomatic, early-stage chronic lymphocytic leukemia.American Society of Hematology

Risk Factors

Many leukemia cases do not have an identifiable cause, but people exposed to ionizing radiation, such as atomic bomb survivors and patients receiving chemoradiation therapy for other cancers, have an increased risk of developing acute and chronic myelogenous leukemia and acute lymphoblastic leukemia.2,3 Individuals exposed to Agent Orange are at higher risk of developing chronic lymphocytic leukemia.4 Cumulative exposure to ionizing radiation from computed tomography increases the risk of leukemia, especially in children, although the risk is small.5 In children younger than five years, the incidence of leukemia is 1 in 5,250 head scans, whereas the incidence in children 10 to 14 years of age is 1 in 21,160 head scans.6

Long-term exposure to benzene, a chemical found in tobacco smoke, motor vehicle exhaust, and some pesticides, is a known risk factor for leukemia, especially acute myelogenous leukemia.7 Using hair dye does not appear to increase the risk of leukemia.8 People with genetic disorders, including Down syndrome, Klinefelter syndrome, and Fanconi anemia, are at higher risk of developing acute leukemia.2,3 About 30% of patients with myelodysplastic syndrome will develop a secondary leukemia, most likely acute myelogenous leukemia.2 Patients with hepatitis C virus infection have a higher incidence of chronic lymphocytic leukemia.4 Obesity is a risk factor for leukemia and adversely affects overall survival.9,10

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