ACUTE MYELOID LEUKEMIA
Acute myeloid leukemia also known as acute myeloyenous leukemia or acute non-lymphocytic leukemia (ANLL) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells.
Acute myeloid leukemia is the most common acute leukemia affecting adults, and its incidence increase, with age. Although AML is a relatively rare disease, accounting for approximately 1.2% of cancer death in the United States, (Jemal et al., 2002), its incidence is expected to increase as the population ages.
The symptoms of AML are caused by replacement of normal bone marrow with leukemia cells, which cause a drop in red blood cells, platelets, and normal white blood cells.
These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Several risk factors and chromosomal abnormalities have been identified but the specific cause is not clear. As acute leukemia progresses rapidly and is typically fatal within weeks or months if left untreated.
AML has several subtypes; treatment and prognosis varies among subtypes. Five-years survival varies from 15-70%, and relapse rate varies from 33-78% depending on subtype.
AML is treated initially with chemotherapy aimed at inducing a remission; patients may go on to receive additional chemotherapy or a haematopoietic stem transplant. Recent research into the genetics of AML has resulted in the availability of tests that can predict which drug or drugs may work best for a particular patient, as well as how long that patient is likely to survive.
Classification of Acute Myeloid Leukemia
The two most commonly used classification schemata for AML are the older French-American-British (FAB) system and the new World Health organization (WHO) system.
World Health Organisation (WHO)
The World Health organization (WHO) classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than th FAB criteria. Each of the WHO categories contains numerous descriptive subcategories of interest to the haematopathologist and oncologist. However, most of the clinically significant information in the WHO schemata is communicated via categorization into one of the subtypes listed below:
Table 2.1: The WHO subtypes of AML are: (Vardiman et al., 2002)
|Acute myeloid leukemia||· AML with translocation between chromosome 8 and 21 (t(8;21) (ICD-09896/3); RUNX1/RUNX1T1(Runt-related transcription factor 1;translocated to,1)· AML with invasions in chromosomal [inv(16)] (ICD-09871/3); CBFB/MYH11
· APL with translocation between chromosome 15 and 17[t(15;17)] (ICD-0986613); RARA; PML
· AML with translocations in chromosomes a and 11 [t(9;11)]; MLLT3-MLL
|AML with multilineage dysplasia||Patients with AML in this category generally have a high rate of remission and a better prognosis compared to other types of AML. This category includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into AML. This category of AML occurs most often in elderly patients and often has a worse prognosis.|
|AML and MDS, therapy related||This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop AML or MDS. These leukemias may be characterised by specific chromosomal abnormalities, and often carry a worse prognosis.|
|AML not otherwise categorized||Includes subtypes of Acute myeloid leukemia that do fall into the above categories.|
Acute leukemias of ambiguous lineage (also known as mixed phenotype or biphenotypic acute leukemia) occur when the leukemia cells cannot be classified as either myeloid or lymphoid cells, or where both cell types are present.
The French-American-British (FAB) classification system divides AML into eight subtypes, M through to M7, based on the type of cell from which leukemia developed and its degree of maturity. This is done by examining the appearance of the malignant cells with light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities. The subtypes have varying prognoses and responses to therapy. Although the WHO classification (see above) may be more useful, the FAB system is still widely used.
Table 2.2: Eight FAB subtypes were proposed in 1976. (Bennett et al., 1976).
|Type||Name||Cytogenetics||Percentage of adult AML patients|
|M||Minimally differentiated acute myeloblastic leukemia||5%|
|M1||Acute myeloblastic leukemia, without maturation||15%|
|M2||Acute myeloblastic leukemia, with granulocytic maturation||t(8,21) (q22;922),t (6,9)||25%|
|M3||Promyelocytic, or acute promyelocytic leukemia (APL)||t (15;17)||10%|
|M4||Acute myelomonocytic leukemia||inv (16), (p13q22), del(16q)||20%|
|M4eo||Myelomonocytic together bone marrow eosinophilia||inv (16), t (16;16)||5%|
|M5||Acute monoblastic leukemia (M5a) or acute monocytic leukemia||(M56) del (11q) + (9;19)||10%|
|M6||Acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b)||5%|
The morphologic subtypes of AML also include rare types not included in the FAB systems, such acute basophilic leukemia, which was proposed as ninth subtype, M8, in 1999 (Duchayne et al., 1999).
SIGNS AND SYMPTOMS OF AML
Diffusely swollen gums due to infiltration by leukemia cells in a person with acute myelomonocytic leukemia. Most signs and symptoms of AML are caused by the replacement of normal blood cells with leukaemic cells. A lack of normal white blood cell production makes the patient susceptible to infections; while the leukaemic cells themselves are derived from white blood cell precursors, they have no infection-fighting capacity. (Hoffman et al., 2005).
A drop in red blood cell count (anemia) can cause fatigue, paleness, and shortness of breath. A lack of platelets can lead to easy bruising or bleeding with minor trauma.
The early signs of AML are often vague and non specific, and may be similar to those of influenza or other common illness, some generalised symptoms include:
- Weight loss
- Loss of appetite
- Sshortness of breath
- Easy bruising or bleeding
- Petechiae (flat, pin-head sized spots caused by bleeding )
- Bone and joint
- Persistent or frequent infection. (Hoffman et al., 2005).
Enlargement of the spleen may occur in AML but it is typically mild and asymptomatic, lymph node swelling is rare in AML, in contrast acute lymphoblastic leukemia. The skin involved about 10% of the time in the form of leukemia cutis. Rarely, Sweet’s syndrome, a paraneoplastic inflammation of the skin, can occur with AML. (Hoffman et al. 2005).
Some patients with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Rarely, the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow, called chloroma. Occasionally, a person may show no symptom, and the leukemia may be discovered incidentally during a routine blood test.
CAUSES OF ACUTE MYELOID LEUKEMIA
A number of risk factors for developing AML have been indentified, including: other blood disorders, chemical exposures, ionizing radiation, and genetics.
Preleukemic blood disorder, such as myelodysplastic syndrome or myeloproliferative disease, can evolve into acute myeloid leukemia, the exact risk depends on the type of MDS/MPS. (Sanz et al.,1989).
Exposure to anticancer thermotherapy, in particular alkylating agents, can increase the risk of subsequently developing AML. The risk is the highest, about three to five years after chemotherapy. (LeBeau et al., 1986). Other chemotherapy agents, specifically epipodephyllotoxins and anthracyclines, have also been associated with treatment-related leukemia. These treatment-related leukemias are often associated with special chromosomal abnormalities in the leukemia cells. (Thirman et al., 1993). Occupational chemical exposure to benzene and other aromatic organic solvents is controversial as cause of AML. Benzene and many of its derivatives are known to be carcinogenic in vitro. While some studies have suggested a link between occupational exposure to benzene and increased risk of AML, (Austin et al., 1988). Others have suggested the attributable risk, if any, is slight (Linet, 1985).
Ionizing radiation exposure can increase the risk of AML. Survivours of the atomic bombings of Hiroshima and Nagaski had an increased rate of AML. (Bizzozero et al., 1966), as did radiologists exposed to high levels of x-rays prior to the adoption of modern radiation safety practices. (Yoshinaga et al., 2004).
A hereditary risk for AML appears to exist. Multiple cases of AML developing in a family at a rate higher than predicted by chance alone have been reported. (Taylor et al., 1986). The risk of developing AML increased three fold in first degree relatives of patients with AML. (Gunz et al., 1969)
Several congenital conditions may increase the risk of leukemia; the most common is probably Down Syndrome which is associated with a 10-to18-fold increase in the risk of AML. (Evans et al., 1972).