Acute Myelogenous Leukemia

Acute Non-Lymphocytic Leukemia (ANLL); Acute Myelogenous Leukemia (AML)

Definition = clonal malignant disorder of the hematopoietic stem cell characterized by the proliferation of abnormal (leukemic) blast cells and the suppression of normal hematopoiesis.

Incidence – predominant type of leukemia in the neonatal period and in adults where the incidence steadily Ý with age.

Etiology

de novo acute leukemia – unknown

secondary acute leukemia (poor prognosis) – ?radiation exposure (seen in Hiroshima survivors); chemicals (benzene, alkylating agents); genetic predisposition (Down’s syndrome, Fanconi’s anemia and Bloom’s syndrome); end stage of other disorders (myeloproliferative disorders, myelodysplasia, PNH)

Pathophysiology – malignant transformation of a single stem cell followed by clonal proliferation and accumulation

Clinical features

leukemic cell proliferation Þ bone pain, skin or gum infiltration; lymphadenopathy, hepatosplenomegaly; infiltration of peripheral nerves, CNS; hyperleukocytosis (CBC demonstrates circulating blasts); presence Auer rod = AML

bone marrow failure Þ anemia (exercise intolerance, CHF); thrombocytopenia (bleeding, bruising or a petechial rash); granulocytopenic (infection); Ý Ý WBC – hyperleukocytosis (respiratory distress, stupor, CNS bleeds, retinal engorgement, priapism); metabolic and electrolyte abnormalities

Lab features: anemia (normochromic, normocytic), ß reticulocytes, thrombocytopenia; circulating blasts in blood; difficult to differentiate from ALL by morphology alone, although auer rods (found in approx 30% of cases) confirm ANLL

Cytochemistry in Acute Leukemia: myeloperoxidase, sudan black, non-specific esterase Þ + in AML and not in c-ALL and T-ALL; Periodic acid-Schiff is + in c-ALL and AML.

Chromosome abnormality: Philadelphia chromosome – t(9;22); Others – t(8;21), t(15;17), del(5q), del(7q), inv(16)

Morphological classification: M1-acute myeloblastic without maturation; M2-acute myeloblastic with maturation (most common subtype), usually t(8;21) with Auer rods; M3-acute promyelocytic; M4-acute myelomonocytic (2^nd most common); M5-acute monocytic; M6-acute erythroleukemia; M7-acute megakaryoblastic

Acute promyelocytic leukemia (M3): 10% of ANLL; median age 31 yrs; >30% promyelocytes in marrow; coagulopathy (DIC); t(15;17) resulting in abnormalities of the retinoic acid receptor located on chrom 17; Treatment = trans-retinoic acid

Therapy

Remission induction: goal – eradicate all leukemic cells; intensive chemotherapy; complications – prolonged myelosuppression, bleeding, infection; results – complete remission in 90% of children, 70% young adults, 50% middle aged adults, 30% of elderly

Post remission therapy: essential to prevent relapse; intensive chemotherapy; ? bone marrow transplantation (auto or allo); long term disease free survival – 25% of adults with CR, 60% of children with CR

Good prognosis – young age, low white count and certain chrom abnormalities (t8;21, inv 16)

Poor prognosis – elderly patients; secondary leukemias; abnormalities of chr 5, 7 or Ph1 chrom; complicating medical illnesses.