Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
- John Anastasi, MD
John Anastasi, MD
- Associate Professor
- University of Chicago
Acute myeloid leukemia (AML, also known as acute myelogenous leukemia) consists of a group of relatively well-defined hematopoietic neoplasms involving precursor cells committed to the myeloid line of cellular development (ie, those giving rise to granulocytic, monocytic, erythroid, or megakaryocytic elements).
AML is characterized by a clonal proliferation of myeloid precursors with a reduced capacity to differentiate into more mature cellular elements. As a result, there is an accumulation of leukemic blasts or immature forms in the bone marrow, peripheral blood, and occasionally in other tissues, with a variable reduction in the production of normal red blood cells, platelets, and mature granulocytes. The increased production of malignant cells, along with a reduction in these mature elements, results in a variety of systemic consequences including anemia, bleeding, and an increased risk of infection. (See "Pathogenesis of acute myeloid leukemia".)
The presenting signs and symptoms and diagnosis of AML will be reviewed in this topic. The subclassification, prognosis, cytogenetics, treatment, and complications of AML and issues related to one of the AML variants, acute promyelocytic leukemia (AML-M3), are discussed separately. (See "Classification of acute myeloid leukemia" and "Prognosis of acute myeloid leukemia" and "Cytogenetics in acute myeloid leukemia" and "Induction therapy for acute myeloid leukemia in younger adults" and "Treatment of acute myeloid leukemia in older adults" and "Overview of the complications of acute myeloid leukemia" and "Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults".)
AML is the most common acute leukemia in adults and accounts for approximately 80 percent of cases in this group [1,2]. In the United States and Europe, the incidence has been stable at 3 to 5 cases per 100,000 population [3-5]. In contrast, AML accounts for less than 10 percent of acute leukemias in children less than 10 years of age.
In adults, the median age at diagnosis is approximately 65 years. The incidence increases with age with approximately 1.3 and 12.2 cases per 100,000 population for those under or over 65 years, respectively. The male:female ratio is approximately 5:3. This incidence is similar among persons of different races. In one study, non-Hispanic Whites had the highest incidence (4 cases per 100,000 population), while Hispanic Whites, Blacks, and Asian Pacific Islanders had a slightly lower incidence (3 cases per 100,000 population) .
- Yamamoto JF, Goodman MT. Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997-2002. Cancer Causes Control 2008; 19:379.
- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017.
- Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116:3724.
- Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011; 105:1684.
- Dores GM, Devesa SS, Curtis RE, et al. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood 2012; 119:34.
- Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62:10.
- Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 2005; 104:788.
- Nebgen DR, Rhodes HE, Hartman C, et al. Abnormal Uterine Bleeding as the Presenting Symptom of Hematologic Cancer. Obstet Gynecol 2016; 128:357.
- Daly PA, Schiffer CA, Wiernik PH. Acute promyelocytic leukemia--clinical management of 15 patients. Am J Hematol 1980; 8:347.
- Ratnam KV, Khor CJ, Su WP. Leukemia cutis. Dermatol Clin 1994; 12:419.
- Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood 2011; 118:3785.
- Desai A, Desai A, Staszewski H, Cunha BA. An unusual initial manifestation of acute leukemia. Am J Med 2012; 125:1173.
- Castagnola C, Nozza A, Corso A, Bernasconi C. The value of combination therapy in adult acute myeloid leukemia with central nervous system involvement. Haematologica 1997; 82:577.
- Cassileth PA, Sylvester LS, Bennett JM, Begg CB. High peripheral blast count in adult acute myelogenous leukemia is a primary risk factor for CNS leukemia. J Clin Oncol 1988; 6:495.
- Dekker AW, Elderson A, Punt K, Sixma JJ. Meningeal involvement in patients with acute nonlymphocytic leukemia. Incidence, management, and predictive factors. Cancer 1985; 56:2078.
- Shihadeh F, Reed V, Faderl S, et al. Cytogenetic profile of patients with acute myeloid leukemia and central nervous system disease. Cancer 2012; 118:112.
- Blum W, Mrózek K, Ruppert AS, et al. Adult de novo acute myeloid leukemia with t(6;11)(q27;q23): results from Cancer and Leukemia Group B Study 8461 and review of the literature. Cancer 2004; 101:1420.
- Williford SK, Salisbury PL 3rd, Peacock JE Jr, et al. The safety of dental extractions in patients with hematologic malignancies. J Clin Oncol 1989; 7:798.
- Byrd JC, Mrózek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100:4325.
- Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002; 94:1739.
- Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 1995; 13:1800.
- Neiman RS, Barcos M, Berard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981; 48:1426.
- Paydas S, Zorludemir S, Ergin M. Granulocytic sarcoma: 32 cases and review of the literature. Leuk Lymphoma 2006; 47:2527.
- Choi EK, Ha HK, Park SH, et al. Granulocytic sarcoma of bowel: CT findings. Radiology 2007; 243:752.
- Seok JH, Park J, Kim SK, et al. Granulocytic sarcoma of the spine: MRI and clinical review. AJR Am J Roentgenol 2010; 194:485.
- Shinagare AB, Krajewski KM, Hornick JL, et al. MRI for evaluation of myeloid sarcoma in adults: a single-institution 10-year experience. AJR Am J Roentgenol 2012; 199:1193.
- Tsimberidou AM, Kantarjian HM, Wen S, et al. Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia. Cancer 2008; 113:1370.
- Mizock BA, Franklin C, Lindesmith P, Shah PC. Confirmation of spurious hypoxemia using continuous blood gas analysis in a patient with chronic myelogenous leukemia. Leuk Res 1995; 19:1001.
- Kaleem Z, Crawford E, Pathan MH, et al. Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med 2003; 127:42.
- Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood 2008; 111:3941.
- Baer MR, Stewart CC, Dodge RK, et al. High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361). Blood 2001; 97:3574.
- Haferlach T, Kohlmann A, Wieczorek L, et al. Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol 2010; 28:2529.
- Yendamuri S, Calin GA. The role of microRNA in human leukemia: a review. Leukemia 2009; 23:1257.
- Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127:2391.
- Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115:453.
- van den Ancker W, Westers TM, de Leeuw DC, et al. A threshold of 10% for myeloperoxidase by flow cytometry is valid to classify acute leukemia of ambiguous and myeloid origin. Cytometry B Clin Cytom 2013; 84:114.
- CLINICAL PRESENTATION
- Central nervous system
- Myeloid sarcoma
- METABOLIC AND ELECTROLYTE ABNORMALITIES
- PATHOLOGIC FEATURES
- Peripheral blood
- Bone marrow biopsy and aspirate
- - Blast count
- - Cell origin
- - Bone marrow infiltration
- - Cytogenetic features
- - Molecular studies
- DIFFERENTIAL DIAGNOSIS
- WHO CLASSIFICATION
- INFORMATION FOR PATIENTS