Acute Leukemia

Definition

• Clonal proliferation of hematopoietic precursor with i ability to differentiate into mature elements • I blasts in bone marrow and periphery -» I RBCs. platelets, and neutrophils

Epidemiology and risk factors

• Acute myelogenous leukemia (AML): -12.000 cases y; median age 65 y; >80% of adult acute leukemia cases

• Acute lymphocytic leukemia (ALL): 4000 cases y, median age 10 y; bimodal with

2nd peak in elderly

• Risk factors: radiation, chemotherapy (alkylating agents and topoisomerase II

inhibitors), benzene, smoking

• Acquired hematopoietic diseases: MDS, MPD (especially CML), aplastic anemia, PNH

• Inherited: Down's & Klinefelters, Fanconis anemia, Bloom syndrome, ataxia telangiectasia

Clinical manifestations

• Cytopenias — fatigue (anemia), infection (neutropenia), bleeding (thrombocytopenia)

leukostasis (when blast count >50.000 |xl): occluded microcirculation -» local hypoxemia and hemorrhage — headache, blurred vision.TIA CVA, dyspnea, hypoxia; look for hyperviscosity retinopathy (vascular engorgement, exudates, hemorrhage) DIC (especially with APML)

leukemic infiltration of skin, gingiva (especially with monocytic subtypes M4 and M5) chloroma: extramedullary tumor of leukemic cells, virtually any location

bone pain, lymphadenopathy, hepatosplenomegaly (also seen in monocytic AML) CNS involvement ( -15%): cranial neuropathies, nausea and vomiting, headache anterior mediastinal mass (especially inT-cell ALL) tumor lysis syndrome (see "Oncologic Emergencies")

Diagnostic evaluation

• Peripheral smear anemia, thrombocytopenia, variable WBC (50% p w T WBC.

50% p w normal or i WBC) * circulating blasts (seen in >95%)

• Bone marrow: hypercellular with >20% blasts; cytogenetics, flow cytometry

• Tumor lysis syndrome (rapid cell turnover): î UA, I LDH, î K, î PO«, 1 Ca

• Coagulation studies to r o DIC: PT. PTT, fibrinogen. D-dimer

• LP (w co-admin of intrathecal chemotherapy to avoid seeding CSF w circulating blasts) for all Pts (CNS is sanctuary site) and for AML w CNS sx

• TTE if prior cardiac history or before use of anthracydines

• HLA typing of Pt. siblings, and parents for potential allogeneic HSCT candidates

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