General Information
Advances in the treatment of adult acute myeloid leukemia (AML; also called
acute nonlymphocytic leukemia or ANLL) have resulted in substantially improved
complete remission rates.[1] 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 15% of adults with AML (about 25% 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 >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 syndrome. Leukemias that
express the progenitor cell antigen CD34 and/or the P-glycoprotein (MDR1 gene
product) have an inferior outcome.[2-4]
Cytogenetic analysis provides some of the strongest prognostic information
available, predicting outcome of both remission induction and postremission
therapy.[5] Cytogenetic abnormalities that indicate a good prognosis include
t(8;21), inv(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 predict clinical
outcome in elderly patients with AML as well as in younger patients.[6] The
fusion genes formed in t(8;21) and inv(16) can be detected by
reverse-transcriptase polymerase chain reaction (RT-PCR), 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.[7]
The classification of AML has been revised by a group of pathologists and clinicians under the auspices of the World Health Organization (WHO).[8] 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.[8-10] Each criterion has prognostic and treatment implications but, for practical purposes, antileukemic
therapy is similar for all subtypes.
Long-term follow-up of 30 patients with AML 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.[11] The differentiation of AML from acute lymphocytic leukemia has important
therapeutic implications. Histochemical stains and cell
surface antigen determinations aid in discrimination.
References
- Scheinberg DA, Maslak P, Weiss M: Acute leukemias. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2001, pp 2404-32.
- 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]
- 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]
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