Term
| what is the definition of acute leukemia? |
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Definition
| a block or arrest on maturation leading to accumuation of immature cells (myeloblasts/lymphoblasts) in the bone marrow/blood. these have a high N:C ratio, are larger and have nucleoli present |
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Term
| what are the histological differences between myeloblasts and lymphoblasts? |
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Definition
| myeloblasts have flattened nuclei and are larger, both have visible nucleoli |
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Term
| what is a myeloblast with visible granules called? |
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Definition
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Term
| what is AML characterized by? |
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Definition
| massive accumulation of blast cells in marrow (>20%), which is fatal if untreated, incidence rises sharply with age and long-term survival rate is 20-40% for adult-onset leukemias |
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Term
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Definition
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Term
| what are risk factors for AML? |
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Definition
| chemicals (benzene)/radiation, cytoxic drugs used in CA therapy, genetic factors (down's syndrome pts @ increased risk), and infection with certain viruses (human T-cell lymphotropic virus type 1- HTLV-1 and EBV) |
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Term
| who gets AML slightly more? |
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Definition
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Term
| what does the multistep process of AML pathobiology consist of? |
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Definition
| genetic changes in hematopoietic precursor cells and uncoupling of normal hematopoietic growth and differentiation (tumor suppressor genes/oncogenes) |
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Term
| what are 2 common translocations that lead to AML? |
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Definition
| t(15:17) M2, and t(8:21) M3 |
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Term
| what is characteristic of chemo-induced AML? |
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Definition
| accumulation of additional genetic lesions - classically after alkylating agents. the latency period varies (generally around 15 yrs) |
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Term
| what is significant about acute promyelocytic leukemia? what is the treatment specific for it? |
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Definition
| it is caused by a unique translocation involving RAR alpha on chromosome 17, t(15:17), a chimeric fusion transcript. this causes RAR alpha to bind to the retinoid X receptor -> the resulting heterodimer then binds to retioic acid reponsive elements and regulate transcription. it is treated with high dose retionic acid, which can help unblock leukemias and progress forward |
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Term
| how does AML present clinically? |
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Definition
| bruising, nonspecific fatigue, weakness, fever, weight loss, epistaxis |
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Term
| what are dx tests for AML? |
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Definition
| *CBC, differential coagulation -including fibrinogen (tendency for DIC w/AML), blood electrolytes/chemistry (including creatinine, uric acid, calcium and phosphorus), examination of peripheral blood smear, examination of bone marrow aspirate smear/bx, leukemia blast cell surface phenotype (cytogenics and molecular genetics, and examination of CSF if indicated |
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Term
| what is the dx profile for AML? |
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Definition
| anemia, thrombocytopenia (bone marrow being replaced w/leukemia cells), WBC count can be normal/reduced/elevated (b/c they may just stay in the marrow), peripheral smear should show blasts, blood chemistry should be normal (but there may be elevated creatinine - evidence of adavanced disease), and a **bone marrow bx is needed to make a final dx |
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Term
| what type of AML has the highest incidence? |
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Definition
| M2 @ 25% (has myeloblasts with some maturation and t(8:21)), the next is M4 @ 20% (has no distinct genetic pattern) |
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Term
| what are prognostic factors for AML? |
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Definition
| age (older: worse), antecedent hematological disorder/secondary AML (more complex cytogenetics), complex cytogenetics, poor performance status (high comorbidity), multidrug resistance (encodes p glycoprotein transmembranous protein “pumps out” chemotherapy ), high WBC at dx (extremely low is also bad) |
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Term
| what is the survival rate for pts with AML? |
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Definition
| 60% 5 yrs, 70-80% will have a complete response (leukemia is undetectable), 25-30% will be cured |
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Term
| what is the treatment goal for AML? |
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Definition
| eradication of leukemic clone and re-establishment of normal hematopoiesis |
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Term
| what is the induction phase of chemo? consolidation phase? |
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Definition
| induction: goal is to induce a CR (<5% blasts, may be mult rounds). consolidation: lengthen CR, eradicate residual leukemic cells |
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Term
| what is the chemotherapy used for AML? |
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Definition
| anthracycline (tetracyline/topoisomerase II) and cytaramine (pyrimidine antimetabolite) and intensive postremission therapy is required for CR (no maintenance usually needed) |
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Term
| what is the specific treatment regimen for AML? |
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Definition
| 3+7 regimen, usually daunorubicin for 3 days, Ara-C for 7 (maybe have to be repeated to induce a full CR). (cardiotoxicity is dose dependent on anthracycline) |
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Term
| who does ALL generally occur in? what are clinical symptoms? |
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Definition
| children under the age of 13. clinical symptoms of liver/spleen/node enlargement, cytopenias, and *bone pain |
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Term
| what are the FAB classifications of ALL? |
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Definition
| L1 (small cells predominate), L2 (large cells predominate), L3 (large homogenous cells) |
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Term
| what is the more common leukemia? |
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Definition
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Term
| what are some general characteristics of chronic leukemias? |
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Definition
| no maturation arrest - *but not functional, predominance of mature (myeloid/lymphoid) cells (commonly named by by the predominant cell), and it occurs in older pts. they are much more common and manageable (all doctors except pediatricians will see it) |
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Term
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Definition
| clonal expansion of the myeloid lineage with *basophila (one of the few times you see this) and *splenomegaly. it is due to the philadelphia chromosome t(9:22) (bcr-abl rearrangement) and makes up 15-20% of all adult leukemias |
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Term
| what are the 3 phases of CML? |
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Definition
| chronic phase (3-4 yrs, high WBC), accelerated phase (progressive maturation arrest, therapy resistance, more blasts in marrow, as the WBC count increases it will basically become acute leukemia), and blast crisis |
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Term
| what are clinical features of CML? |
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Definition
| splenomegaly (generally asymptomatic, but early satiety can occur with impinging on stomach or upper L quadrant pain), anemia, hepatomegaly, purpura, fatigue, anorexia, weight loss, sweats, hyperleukocytosis (^WBC), and priapism |
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Term
| what laboratory tests are done for suspected CML pts? |
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Definition
| LAP (leukocyte alkaline phosphatase which stains granulocytes for counting - high = reactive/low = CML), bcr:abl gene test (should be 0), and bone marrow bx (more important for lymphoma) and aspirate (more important for leukemia) |
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Term
| if a bone bx is really hard and white what is it likely? |
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Definition
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Term
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Definition
| a drug which binds to the promoter region of the bcr:abl gene, preventing ATP from binding and cuasing the translocation -> is effective at all stages of CML. resistance can develop, but there are secondary drugs available |
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Term
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Definition
| a predominance of mature lymphocytes, which is exceedingly common in men >60. it has a low risk of thrombosis (high WBC counts are not as bad as with ALL/AML, these cells are small, relatively mature and non-sticky) |
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Term
| what is the clinical presentation for pts with CLL? |
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Definition
| some are asymptomatic, lymphadenopathy, splenomegaly (very big), night sweats, fatigue, ealy satiety, bruising, and exaggerated response to insect bites |
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Term
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Definition
| the classification of the 4 stages of CML with nodes/spleen/liver/anemia being stage 4 and lymphocytosis being stage 1 |
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Term
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Definition
| no, but pts generally do well for a good amount of time |
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Term
| what is the therapy for CLL? |
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Definition
| none, fludarabine, alkylating agents, ritumimab, alemtuzumab and ofatumimab |
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