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28 Cards in this Set
- Front
- Back
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CML
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Cancer of the white blood cells
Malignant cell is relatively immature stem cell Result is excess production of mature cells of multiple lineages |
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CBC for CML
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Elevated total white cell count
Differential reveals elevated numbers of neutrophils, bands, myelocytes, metamyelocytes, eosinophils, basophils, platelets |
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Diagnosing CML
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Find the Philadelphia chromosome
t(9;22) Chromosome 9: abl gene (Abelson leukemia virus) Chromosome 22: bcr gene (breakpoint cluster region) |
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abl protein
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The abl protein is a tyrosine kinase, which is an enzyme involved in signal transduction
When the t(9;22) is present, the tyrosine kinase is always phosphorylated (ie always “on”) This provides a constant signal to certain pathways that results in cell growth that exceeds apoptosis |
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chromosome 22 and bcr gene
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Chromosome 22 can break in different regions within the bcr gene, resulting in different sizes of bcr-abl protein products:
p190 (190 kDa protein): seen in ALL p210 (210 kDa protein): seen in CML |
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Different phases of CML
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Chronic phase: <5% blasts in the marrow
Accelerated phase: Many different criteria 5-20% blasts in the marrow Blast crisis: >20% blasts in the marrow Just like any other acute leukemia Can be myeloid or lymphoid (flow cytometry) |
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Treatment of CML past and present
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Pre-Gleevec era:
High dose interferon Very toxic: fever, flu-like symptoms, fatigue Allogeneic stem cell transplant Very high associated morbidity and mortality Gleevec (imatinib mesylate) TKI (tyrosine kinase inhibitor) STI (signal transduction inhibitor) Small molecule inhibitor Pill taken once a day Side effects: Mild nausea and vomiting Periorbital edema Pleural effusions Well-tolerated |
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Gleevec
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Binds to c-kit
On GISTs (GI stromal tumors) Binds to PDGFR-alpha Seen in hypereosinophilic syndrome FDA approved in 2001 for CML No real long term follow-up Gleevec resistance is developing Some via T315I mutations |
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Second generation Tyrosine Kinase inhibitors
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Dasatinib
Nilotinib Neither are effective against the T315I mutation |
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treament of accelerated phase
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Gleevec
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Blast crisis
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treated like the acute leukemia
Myeloid blast crisis: “7+3” cytarabine x 7 days with daunorubicin x 3 days Lymphoid blast crisis: Complex multi-agent chemotherapy regimen; exactly what we would use for de novo ALL |
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CLL
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Cancer of the white blood cells
Malignant cell is more differentiated than CML Results in excess numbers of mature-appearing lymphocytes Continuum with SLL (small lymphocytic lymphoma) that has no circulating neoplastic cells and resides in lymph nodes |
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CBC for CLL
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Elevated total white cell count
Differential is primarily lymphocytic Hemoglobin and platelets are normal Except in advanced stages of disease when Hb and platelets can be low |
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Diagnosis of CLL
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Peripheral blood sample for flow cytometry
Do not need a bone marrow for diagnosis (+) CD5, CD19, CD23 (+/-) CD20 (weak expression) (+) surface immunoglobulin Light chain restriction Only kappa or lambda, not both Send chromosomal studies to get information on prognosis |
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steroids are only cytotoxic to
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lymphoid cells
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p210 kDa protein (bcr-abl)
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indicative of CML
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CLL stage 0
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Lymphocytosis only
>10yr survival low risk |
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CLL stage I
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intermediate risk
Lymphocytosis Lymphadenopathy >8yr survival |
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CLL stage II
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Lymohocytosis, splenomegaly, intermediate risk
~5yr survival |
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CLL stage III
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high risk, lymphocytosis, Hb<11 due to progression of CLL in marrow
Survival 8-12 months |
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CLL sateg IV
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lymphocytosis
plts<100K due to progression of CLL in marrow high risk 8-12 month survival |
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CLL and immune dysregulation
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Difficult to fight infection
Often need prolonged courses of antibiotics Hypogammaglobulinemic Quantitative immunoglobulins often reveal patients to be pan-hypoglobulinemic If patients have persistent infections or infections severe enough to require hospitalization, will treat with IVIG |
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CLL and overactive immune system
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Inappropriate destruction of “self” cells
Autoimmune hemolytic anemia Immune thrombocytopenic purpura Labs for AIHA are the same as with any other: Elevated LDH, bilirubin Low Hb, haptoglobin Can be Coombs positive Generally treat with steroids Don’t need a bone marrow to make this diagnosis |
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Richter’s transformation
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Development of diffuse large B cell lymphoma arising from one CLL clone
May have B symptoms, one area of lymphadenopathy out of proportion to others PET scan will show transformed sites CLL is not PET avid DLBCL is very PET avid Must document with biopsy to prove transformed disease Treat with DLBCL regimen such as R-CHOP CLL chemo is ineffective Pts are still left with underlying CLL after treatment complete |
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Transformation to prolymphocytic leukemia
CLL |
>55% prolymphocytes
Treatment is different from standard CLL treatment |
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CLL treatment
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Chemotherapy
Purine analog based Fludarabine based Pentostatin based Patients are at significant risk for tumor lysis syndrome with the first cycle of treatment Hydration and frequent lab monitoring is important |
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Hairy Cell Leukemia
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Comprises 2% of all leukemias
Very slow-growing B cell malignancy (CD19, 20, 22) Has aberrant expression of T cell marker CD103 TRAP-positive (tartrate-resistant acid phosphatase), a stain Clinically, notable for very large spleens, and dry taps on bone marrows In the bone marrow, cells look like fried eggs Marrow also has lots of fibrosis Treatment is also with purine analogs Cladribine |
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Hairy cell leukemia treatment
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clarabine- purine analog
so slow growing may only get one treatment in a lifetime |
