Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (335 page)

BOOK: Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis
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Bone marrow aspirate and biopsy
are mandatory for cytochemical, immunophenotypic, cytogenetic, and genetic studies. The WHO classification defines AML as with either >20% blasts in bone marrow or PBS or with specific cytogenetic findings: t(8;21)(q22;q22) RUNX1-RUNX1T1; inv(16)p;(13.1q22); 6(16:16)(p13.1;q22 CBFB-MYH11; t(15;17)(q24.1;q21.1) PML-RARA. The bone marrow is hypercellular in most cases, with a predominance of early progenitor cells (myeloblasts and promyelocytes or monoblasts and promonocytes) depending on the leukemic subtype. Initial assessment is based on counting 500 cells on the aspirate. AML–erythroleukemia is established when >50% of precursor cells are erythroid, and myeloblasts comprise >20% of nonerythroid cells. Careful assessment of megakaryocytes and the degree of marrow fibrosis are also part of the initial studies.
   
Coagulation studies.
Bleeding, a severe complication of AML, is usually due to the severe thrombocytopenia, compounded by platelet functional defects. In addition, patients with the t(15;17) and hypergranular promyelocytes frequently develop a proteolytic state akin to DIC either spontaneously or following the initial chemotherapy. The mechanism is thought to be release of tissue factor from the promyelocytes’ granules. PT and PTT are elongated, FDP and latex
D
-dimers are elevated, and fibrinogen, initially elevated, decreases dramatically.
   Metabolic and electrolyte abnormalities are common; the patients must be monitored carefully, especially during induction chemotherapy. Renal failure from multifactorial causes is common.
   Hyperuricemia is the most frequent biochemical abnormality. Hyperuricuria may also be present.
   Tumor lysis syndrome may develop during induction chemotherapy. It is characterized by rapid development of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia.
   Acute promyelocytic leukemia (APL) differentiation syndrome (previously the retinoic acid syndrome) develops in 2–27% of patients in the 1st to 3rd week after initiating all-trans retinoic acid (ATRA) therapy for this type of AML. The most susceptible patients are those with hyperleukocytosis and abnormal serum creatinine. Lactic acidosis has been described in patients with AML.
   Hypokalemia is common and may be profound.
   Lysozyme is released from the leukemic cells and may induce renal tubular damage.
   Hypercalcemia and hypocalcemia have been reported.
   Spuriously high potassium and decreased serum glucose may be the result of circulating metabolically active white cells.
   CNS involvement is infrequent in AML (5–7% of patients). It is more common in patients with a monocytic predominant clone, with hyperleukocytosis, and patients under 2 years of age. MLL rearrangements, inv(16) and complex karyotypes may also predispose to CNS involvement.

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