Term
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Definition
shows symptoms of bone marrow failure:
o Leukostasis – increased viscosity of blood with pulmonary/cerebral effects (SOB at rest)
o Extramedullary disease – myeloblastomas
o Infiltration – leukemic infiltration of skin, gingiva, liver, spleen, lymph nodes, CNS
o DIC – from increased viscosity & platelet dysfunction |
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Term
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Definition
| acquired genetic defect of unregulated myeloid growth w/ limited or no differentiation |
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Term
| diagnosis of AML via lab reports... |
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Definition
| • Lab Dx – patient will have hyperuricemia, hypokalemia, and spurious hypoxemia |
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Term
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Definition
• Etiology – can be a part of a syndrome, or reactive from an insult:
o Radiation, toxins (benzene) – can induce an AML state
o Treatment-related – alkylating agents (cyclophosphamide), topoisomerase II inhibitors
o Congenital DNA Repair Disorders – Fanconi’s syndrome, Bloom’s syndrome
o Myeloproliferative & Myelodysplastic Disorders, Aplastic Anemia – can progress to AML
o Treatment related – alkylating agents (5-7 yrs later), topoisomerase II inhibitors (1-2 years later) |
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Term
| AML prognosis - age, performance, karyotypes, multi-drug resistance? |
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Definition
• AML Prognosis – include age, blast karyotype, MDR phenotype, patient Hx, molecular indicators
o Age – although common in children, increased incidence & severity w/ age
o Performance Status – if patient feels bad, disease prognosis is bad
o Karyotype – certain karyotypes good, others bad prognosis:
t(15;17) – karyotype with good prognosis; associated w/ acute promyelocytic leukemia
t(8;21), inv(16) – other karyotypes with good prognosis (better remission)
5del, 7del, Phl chromosome – poor prognosis
Core binding factors (CBFα and -β) – TFs for blood cell production, lost in t(15;17)
o Multi-Drug Resistant (MDR) Phenotype – have toxin pumps can’t treat as easily! |
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Term
| a mutation in which receptor (not karyotype dependent) => bad prognosis and what does it cause? |
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Definition
• AML Molecular Prognosis – mutations in FLT3 receptor can make for bad prognosis
o FLT3 Activation – mutations in areas of gene will activate receptor
o Function – receptor binds ligand and signals cell growth high WBC, FLT3/ITD+ => bad outcome!
o Prognosis – associated with a worse outcome, and remains negative prognostic factor following HSCT
o Karyotype – associated with normal karyotypes |
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Term
| • CCAAT/CEBPA mutations in both copies => outcome? |
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Definition
| – when both copies are mutated, patients did better than single mutation. |
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Term
| AML ... C-Kit mutation => outcome? |
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Definition
| RTK – high WBC count at dx and higher incidence of extramedullary infiltrates |
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Term
| nucleophosmin1 mutation in AML => outcome? |
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Definition
mutation results in better prognosis
o Mutation – frameshift mutation results in nuclear export signal so protein goes to cytoplasm
o Prognosis – in younger patients with normal cytogenetics, NPM1 mutation predicts favorable prognosis |
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Term
| Induction of AML Treatment: goal, hte actual chemotherapeutic, what's better for children? |
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Definition
induce a complete remission of AML through combination chemotherapy
o Leukemic blast clearance – remove all leukemic blasts by morphologic review
o Anthracycline + Ara-Cytarbine – wipe out marrow (aplasia), an induction chemotherapeutic
o G-CSF Priming – give simultaneously w/ Ara-C, induce cell division (Ara-C only kills dividing)
Bad idea – “priming” hasn’t proven to be helpful except young pts w/ normal karyotype
o MDR Modulation – stop MDR pump from working, but more toxicity elsewhere (bad idea)
o Intense Ara-C – higher doses better in children, who can tolerate more |
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Term
| • Complications of Induction: |
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Definition
| induction of DIC, tumor lysis syndrome, nausea/vomiting, severe myelosuppression, neutropenic infx (pneumonia), mucositis, drug rash, cardiac toxicity, hepatic/renal toxicity, death! |
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Term
| • Post-Remission Therapy – |
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Definition
weigh issues; maintain remission & replenish blood cells:
o More chemotherapy – maintain remission, make sure few remaining leukemic cells don’t resurge
o Bone marrow transplant – need to replenish blood cells eventually, treatment of choice in peds, has better outcomes than chemotherapy, but the toxicity is high esp when donors are exactly matched => relapse!
o Age – young patients easier to get into remission, can take more chemo |
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Term
| Acute promyelocytic Leukemia - histology, genetics, treatment, prognosis, how to treat relapse? |
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Definition
occurs in younger patients, associated with biologically targeted Tx:
o Histology – leukocytes cells are hypergranular with isthmus-shaped nuclei, Auer rods
o Genetics – involves t(15;17) fusion protein
o Treatment – fusion protein can respond to large doses of all trans retinoic acid combined w/ chemo
SEs – capillary leak syndrome (wt gain, hypoxia, pleuropericardial effusions, lung infiltrates, fever); onset day 2 to week 3, hyperluekocytosis, rapidly fatal; treat w/ dexamethasone
Adding arsenic is good! Much better outcomes…can give JUST arsenic => 80% remission! Maybe we don’t need chemotherapy!?
o Prognosis – targeting with RA makes for good prognosis
o Relapse – treat with Arsenic trioxide also moderately successful (same types of SEs as ATRA) |
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Term
| • Acute Lymphoid Leukemia – who? and prognosis factors... |
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Definition
much less common in adults; more common in children
• Prognosis – determined by age, cytogenetics, immunophenotype:
o Age – children 2-9 yo have best prognosis, because like to have t(12;21)
o Cytogenetics – t(12;21) = good prognosis
o Philadelphia Chromosome – can be present in adults w/ ALL (not just CML), poor prognosis
o Immunophenotype – those affecting T cell lineage = better prognosis (than B cell lineage) |
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Term
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Definition
– give an extended induction & post-remission treatment
o Induction – give anthracycline plus steroids, vincristine 2-3 years length of therapy! b/c maintenance therapy is very important! CNS is likely target for relapsing!
o Post-Remission – chemotherapy is prolonged compared to AML; eventually allogenic transplant
o CNS prophylaxis – ALL likes to lie dormant in CNS, need to prevent relapse here |
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Term
| best treatment for Ph Chromosome in ALL |
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Definition
| • Imatinib/Dasatinib + chemo in PhChromosome + ALL= best outcomes! |
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Term
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Definition
| 80-90% can go into remission, but survival poor 30% adults, 70% children; HSCT is recommended in adults w/ high risk features or relapse |
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