Aml 3n6e14

ACUTE

MYELOID

LEUKEMIA Marc Delvin C Quero

Acute Myeloid Leukemia

CLINICAL OVERVIEW • Cancer of blood and bone marrow cells. • It affects myeloid cells. • Blood cell production process is abnormal

• Large numbers of immature myeloid cells are produced. • Acute myeloid leukemia is the most common form of acute

leukemia during the first few months of life.

Acute Myeloid Leukemia

SIGNS AND SYMPTOMS • Fatigue

• Shortness of breath on exertion • Easy bruising • Petechiae • Bleeding in the nose or from the gums • Prolonged bleeding from minor cuts • Recurrent minor infections or poor healing of minor cuts • Loss of appetite or weight loss • Mild fever

Acute Myeloid Leukemia

SIGNS AND SYMPTOMS • Total WBC Count between 5x109/L and 30x109/L with myeloblasts in the peripheral blood smear • Bone and t pain are the first symptoms in 25% of patients. • Elevated serum lysozyme (especially in monocytic subtypes), hyperuricemia (caused by increased cellular turnover), hyperkalemia (caused by cell breakdown), hyperphosphatemia, and hypocalcemia. • Renal failure, tetany, and lethal heart arrhythmias may develop.

Acute Myeloid Leukemia

RISK FACTORS •Age Older adults are more likely to develop AML

•Smoking 20% of AML cases are linked to smoking Doubles the risk of disease in people older than 60

•Genetic disorders Down syndrome, Fanconi’s anemia

Acute Myeloid Leukemia

RISK FACTORS •High doses of radiation Long-term survivors of atomic bombs

•Previous chemotherapy treatment Breast cancer, ovarian cancer, lymphoma

•Exposure to industrial chemicals Benzene

Acute Myeloid Leukemia

CLINICAL OVERVIEW

Acute Myeloid Leukemia

CLINICAL OVERVIEW

Acute Myeloid Leukemia

WHO CLASSIFICATION

•Acute myeloid leukemia with recurrent genetic abnormalities •Acute myeloid leukemia with t(8;21)(q22;q22), (AML1/ETO) •Acute myeloid leukemia with abnormal bone marrow eosinophils and inv(16)(p13q22) or t(16;16)(p13;q22), (CBFb/MYH11) •Acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RARa) and variants •Acute myeloid leukemia with 11q23 (MLL) abnormalities •Acute myeloid leukemia with multilineage dysplasia •Following MDS or MDS/MPD •Without antecedent MDS or MDS/MPD, but with dysplasia in at least 50% of cells in two or more myeloid lineages •Acute myeloid leukemia and myelodysplastic syndromes, therapy-related •Alkylating agent, radiation-related type •Topoisomerase II inhibitor–related type (some may be lymphoid) •Others •Acute myeloid leukemia, not otherwise categorized; classify as: •Acute myeloid leukemia, minimally differentiated •Acute myeloid leukemia without maturation •Acute myeloid leukemia with maturation •Acute myelomonocytic leukemia •Acute monoblastic, acute monocytic leukemia •Acute erythroid leukemia (erythroid-myeloid and pure erythroleukemia) •Acute megakaryoblastic leukemia •Acute basophilic leukemia

Acute Myeloid Leukemia

DIAGNOSIS Myeloblasts

Monoblasts

Generally have central nuclei with fine, uncondensed chromatin and often prominent nucleoli (usually three to five) but have variable cytoplasm and may have some cytoplasmic granules.

Monoblasts are frequently large with abundant cytoplasm, diffuse chromatin and often prominent nucleoli.

Primitive myeloblasts are identified by monoclonal Monoblasts are characterized by strong reaction antibodies against myeloid-associated antigens with alpha-naphthyl acetate esterase (ANA), which (MPO, CD13, CD33, CD117). is inhibited in monocytes by sodium fluoride as More mature myeloblasts can also be identified by well as alpha-naphthyl butyrate esterase (ANB), or cytochemical reactions with graulocyte-associated antibodies including antilysozyme, CD68, CD64, enzymes using myeloperoxidase, Sudan Black B, and CD36. and ASd-chloroacetate esterase (CAE) assays.

AML requires 20% blasts in blood or marrow for diagnosis.

Acute Myeloid Leukemia

DIAGNOSIS

Acute Myeloid Leukemia

DIAGNOSIS

The presence of the following inclusions is helpful in the diagnosis of AML: Auer rods, eosinophilic rod-like cytoplasmic inclusions derived from myeloperoxidase-positive primary granules. Phi bodies, strings of eosinophilic bead-like granules from catalase-positive microperoxisomes.

Acute Myeloid Leukemia

DIAGNOSIS

Acute Myeloid Leukemia

DIAGNOSIS

Acute Myeloid Leukemia

DIAGNOSIS

Myelocytes Myelocytes

Acute Myeloid Leukemia

DIAGNOSIS

Myeloblasts

Acute Myeloid Leukemia

TREATMENT

A number of chemotherapy medications are effective against AML. Common remission induction regimens include cytarabine (IV) for 7 days, daunorubicin or idarubicin (IV), an anthracycline drug given in a single IV dose for the first three days of treatment. These drugs kill AML cells over the first 7 to 14 days; it then takes the normal bone marrow about 14 days to recover and produce normal blood cells again. Post-remission therapy includes additional chemotherapy or a stem cell transplant.

Acute Myeloid Leukemia

SOURCES

Rodak, B., Fritsma, G., and Doig, K. Hematology: Clinical Principles and Applications. 3rd Ed. Mherson, R., and Pincus, M. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st Ed. Pollyea DA, Kohrt HE, Medeiros BC. Acute myeloid leukaemia in the elderly: a review. Br J Haematol 2011; 152:524.

Fernandez HF. New trends in the standard of care for initial therapy of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2010; 2010:56.

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