General Information About Adult Acute Myeloid Leukemia
Incidence and Mortality
Note: Estimated new cases and deaths from acute myeloid leukemia (AML) in the United States in 2013:
- New cases: 14,590.
- Deaths: 10,370.
Advances in the treatment of AML (also called acute myelogenous leukemia, acute nonlymphocytic leukemia [ANLL]) have resulted in substantially improved complete remission (CR) rates. Treatment should be sufficiently aggressive to achieve CR because partial remission offers no substantial survival benefit. Approximately 60% to 70% of adults with AML can be expected to attain CR status following appropriate induction therapy. More than 25% of adults with AML (about 45% of those who attain CR) can be expected to survive 3 or more years and may be cured. Remission rates in adult AML are inversely related to age, with an expected remission rate of more than 65% for those younger than 60 years. Data suggest that once attained, duration of remission may be shorter in older patients. Increased morbidity and mortality during induction appear to be directly related to age. Other adverse prognostic factors include central nervous system involvement with leukemia, systemic infection at diagnosis, elevated white blood cell count (>100,000/mm3), treatment-induced AML, and history of myelodysplastic syndromes or another antecedent hematological disorder. Patients with leukemias that express the progenitor cell antigen CD34 and/or the P-glycoprotein (MDR1 gene product) have an inferior outcome.[2-4] AML associated with an internal tandem duplication of the FLT3 gene (FLT3/ITD mutation) has an inferior outcome that is attributed to a higher relapse rate.[5,6]
Cytogenetic analysis provides some of the strongest prognostic information available, predicting outcome of both remission induction and postremission therapy, as seen in a trial from the Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG) (E-3489). Cytogenetic abnormalities that indicate a good prognosis include t(8; 21), inv(16) or t(16;16), and t(15;17). Normal cytogenetics portend average-risk AML. Patients with AML that is characterized by deletions of the long arms or monosomies of chromosomes 5 or 7; by translocations or inversions of chromosome 3, t(6; 9), t(9; 22); or by abnormalities of chromosome 11q23 have particularly poor prognoses with chemotherapy. These cytogenetic subgroups, as seen in the trial from the Medical Research Council (MRC-LEUK-AML11), predict clinical outcome in older patients with AML as well as in younger patients. The fusion genes formed in t(8; 21) and inv(16) can be detected by reverse transcriptase–polymerase chain reaction (RT–PCR) or fluorescence in situ hybridization (FISH), which will indicate the presence of these genetic alterations in some patients in whom standard cytogenetics was technically inadequate. RT–PCR does not appear to identify significant numbers of patients with good-risk fusion genes who have normal cytogenetics.
The classification of AML has been revised by a group of pathologists and clinicians under the auspices of the World Health Organization (WHO). While elements of the French-American-British classification have been retained (i.e., morphology, immunophenotype, cytogenetics and clinical features), the WHO classification incorporates more recent discoveries regarding the genetics and clinical features of AML in an attempt to define entities that are biologically homogeneous and that have prognostic and therapeutic relevance.[10-12] Each criterion has prognostic and treatment implications but, for practical purposes, antileukemic therapy is similar for all subtypes.
A long-term follow-up of 30 patients who had AML that was in remission for at least 10 years has demonstrated a 13% incidence of secondary malignancies. Of 31 younger-than-40-years, long-term, female survivors of AML or acute lymphoblastic leukemia, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, 2 congenital problems occurred.
The differentiation of AML from acute lymphocytic leukemia has important therapeutic implications. Histochemical stains and cell surface antigen determinations aid in discrimination.References
- American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed October 24, 2013.
- Myint H, Lucie NP: The prognostic significance of the CD34 antigen in acute myeloid leukaemia. Leuk Lymphoma 7 (5-6): 425-9, 1992. [PUBMED Abstract]
- Geller RB, Zahurak M, Hurwitz CA, et al.: Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My10) Br J Haematol 76 (3): 340-7, 1990. [PUBMED Abstract]
- Campos L, Guyotat D, Archimbaud E, et al.: Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79 (2): 473-6, 1992. [PUBMED Abstract]
- Kottaridis PD, Gale RE, Frew ME, et al.: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98 (6): 1752-9, 2001. [PUBMED Abstract]
- Yanada M, Matsuo K, Suzuki T, et al.: Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 19 (8): 1345-9, 2005. [PUBMED Abstract]
- Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96 (13): 4075-83, 2000. [PUBMED Abstract]
- Grimwade D, Walker H, Harrison G, et al.: The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98 (5): 1312-20, 2001. [PUBMED Abstract]
- Mrózek K, Prior TW, Edwards C, et al.: Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study. J Clin Oncol 19 (9): 2482-92, 2001. [PUBMED Abstract]
- Brunning RD, Matutes E, Harris NL, et al.: Acute myeloid leukaemia: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 77-80.
- Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33 (4): 451-8, 1976. [PUBMED Abstract]
- Cheson BD, Cassileth PA, Head DR, et al.: Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 8 (5): 813-9, 1990. [PUBMED Abstract]
- Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 113 (2): 443-5, 2001. [PUBMED Abstract]