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leukemiaHematology An uncommon–incidence, US 3.5/105/yr—malignant clonal expansion of myeloid or lymphoid cells characterized by an ↑ in circulating WBCs; leukemias may be an incidental finding when evaluating an unrelated clinical problem, or when the expansion compromises BM production of one or more cell lines causing anemia, thrombocytopenia, granulocytopenia; leukemias are divided by chronology–acute or chronic, by cell lineage–lymphoid, myeloid/myelocytic, monocytic or megakaryocytic and divided by stage of maturation or cell size Clinical BM infiltration by leukemia, resulting in anemia, thrombocytopenia, granulocytopenia, immune paralysis, ↓ B cells and CD4–helper T cells, ↑ CD8–suppressor T cells, infiltration and leukostasis, cranial nerve palsies, meningitis, lymphadenopathy, hepatosplenomegaly, testicular and cutaneous involvement, metabolic derangements–eg, ↑ Ca2+, K+, LD, ammonia, weight loss, less commonly, autoimmune hemolytic anemia, pallor and arthralgia Diagnosis Hx, physical exam, peripheral smear Management Chemotherapy, RT, BMT. See Accelerated leukemia, Acute leukemia, Acute lymphocytic leukemia, Acute myelocytic leukemia, Acute promyelocytic leukemia, Adult T-cell leukemia-lymphoma, Aleukemic leukemia, Biphenotypic leukemia, Central nervous system leukemia, Chemotherapy-induced leukemia, Chronic leukemia, Chronic lymphocytic leukemia, Chronic myelocytic leukemia, Chronic myelomonocytic leukemia, Congenital leukemia, Erythroleukemia, FAB classification, Hairy cell leukemia, Hand mirror cell leukemia, Herald state of leukemia, Mast cell leukemia, Megakaryoblastic leukemia, Multilineage leukemia, Plasma cell leukemia, Preleukemia, Prolymphocytic leukemia, Promyelocytic leukemia, Smoldering myeloid leukemia.
Leukemia Acute v. Chronic
Acute leukemia More common in children, 80% are ALL, often before age 10, peak at ages 3–7 in whites, ♂:♀ ratio, 1.3:1 Cell types Early pre-B cell 67%; pre-B cell 18%; B cell 1%; T cell 14%; 50-85% are cALLA positive–common acute lymphocytic leukemia antigen, CD10; 5% have Philadelphia chromosome Clinical ALL is more abrupt than AML, with petechial hemorrhage, bone and abdominal pain, headache and vomiting due to ↑ intracranial pressure, lymphadenopathy, splenomegaly, hepatomegaly Lab 70% have low-grade lymphocytosis–< 20 x 109 when diagnosed Evaluation Acute leukemia immunophenotypic profile Specimen EDTA–lavender top tube and sodium heparin–green top tube, peripheral blood smears Method of analysis Flow cytometry, immunofluorecesence Markers measured CD1, -2, -3, -4, -5, -7, -8, -10, -19. -20, -21, -33, -34, -56, megakaryocytic markers, HLA D/DR, kappa, lambda, TdT Management Protocols vary according to standard- or high-risk clinical features, and may include BMT
Chronic leukemia More common in adults/older children, often myelocytic; CML is Philadelphia chromosome positive; may occur < age 5 with myelomonocytosis, anemia, thrombocytopenia, lymphadenopathy; WBC count < 50 x 109, ≠ HbF, ≠ muraminidase; adult CML comprises 20% of all leukemias Clinical Gradual onset of fatigability, anorexia, splenomegaly; lymphadenopathy is uncommon Lab > 25 x 109/L leukemic cells in blood–often an absolute lymphocytosis of > 15 x 1010/L, < 10% blasts in BM, myeloid:erythroid ratio is 10-30:1, 90% of cases have low-to-absent leukocyte alkaline phosphatase and rarely also, ≠ vitamin B12 and B12-binding capacity Evaluation Chronic leukemia immunophenotype profile Specimen EDTA–lavender top tube and sodium heparin–green top tube, peripheral blood smears Method of analysis Flow cytometry, immunofluorescence Markers measured CD3, -5, -19, -20, -21, kappa, lambda Management see Chemotherapy, Induction Prognosis see Remission.
Acute lymphocytic leukemia
Good Age 2-10, CD10 positivity, hyperdiploid karyotype
Poor Age < 2; >10, B-cell phenotype, especially L2 phenotype by FAB classification, presence of chromosome translocations, CNS involvement, mediastinal masses, high initial WBC count
Acute myelocytic leukemia
Good Younger, presence of Auer rods, rapid therapeutic response
Poor Older, prior malignancy or therapy, multiple chromosome defects