General Information
Note: Estimated new cases and deaths from acute myeloid leukemia (AML) in the United States in 2008:[1]
- New cases: 13,290.
- Deaths: 8,820.
Advances in the treatment of AML (also called
acute myelogenous leukemia, acute nonlymphocytic leukemia, or ANLL) have resulted in substantially improved
complete remission rates.[2] Treatment should be sufficiently aggressive to
achieve complete remission because partial remission offers no substantial
survival benefit. Approximately 60% to 70% of adults with AML can be expected
to attain complete remission status following appropriate induction therapy.
More than 25% of adults with AML (about 45% of those who attain complete
remission) 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.[3-5]
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.[6,7]
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 and the Eastern Cooperative Oncology Group (SWOG/ECOG) (S-9034/E-3489).[8] 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-IFI), predict clinical
outcome in older patients with AML as well as in younger patients.[9] 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.[10]
The classification of AML has been revised by a group of pathologists and clinicians under the auspices of the World Health Organization (WHO).[11] 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.[11-13] 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 long-term female survivors of AML or acute lymphoblastic leukemia younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, 2 congenital problems occurred.[14]
The differentiation of AML from acute lymphocytic leukemia has important
therapeutic implications. Histochemical stains and cell
surface antigen determinations aid in discrimination.
References
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American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008.
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Sheinberg DA, Maslak PG, Weiss MA: Acute leukemias. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 2088-116.
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Myint H, Lucie NP: The prognostic significance of the CD34 antigen in acute myeloid leukaemia. Leuk Lymphoma 7 (5-6): 425-9, 1992.
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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.
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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.
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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.
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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.
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