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52 Cards in this Set
- Front
- Back
AML – basic characteristics
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Complex CLONAL disease with considerable phenotypical and genotypical heterogeneity
Proliferation and accumulation of immature haematopoietic cells in the bone marrow and blood Evalutaion and prognosis hase changed over 20 years, however, still most patients will die of the disease or of the therapy. |
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AML - epidemiology
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1,2% of all cancer deaths
Median age at diagnosis: 60-65 years AML: 60-90% of adult leukemias in adults |
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AML - etiology
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No firm etiology factor known at this point. except the regular: smoking inhertance etc.
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Pathogenesis of AML (7)
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Inappropriate proliferation
Differentiation blockade Escape from programmed cell death Self renewal Loss of cell cycle control Genomic instability Leukemia cell dissemination |
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What is a leukemic stem cell?
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only few leukemic blasts have capacity of self renewal. 1 in 10^5 leukemia cells.
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phenotype of leukemia stem cell
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CD34+CD38-
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What differentiation factor is the most comman in AML?
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Transcription factors:
In AML commonly disrupted by chromosomal translocation or point mutations. ---> STOP in differantiation, Increased self renewal capacity |
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Inappropriate proliferation
Which molecules are the most important? Which is expressed in almoast all AML? Other? |
Receptor tyrosine kinase and Intracellular thyrosine kinase are crucial.
FLT3 tyrosine kinase: expressed almost in all AML Other tyrosine kinases involved: c-KIT, JAK-2 etc. |
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How does AML escape apoptosis?
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TK activation-->PI-3 kinase---> Increased BCL-2 (antiapoptotic)
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How is AML classified?
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According to FAB (M0-M7) or WHO classification.
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What is an Auer rod?
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Auer rods can be seen in the leukemic blasts of acute myeloid leukemia. Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts.
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What is an Auer rod?
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Auer rods can be seen in the leukemic blasts of acute myeloid leukemia. Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts.
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Diagnosis of AML, special consideration
Spleen, LN, Skin, mtb and electrolyes. |
Splenomegaly: rare
Lymphadenopathy: rare CNS involvement: 5-7% Skin involvement: 10% Metabolic and electrolyte derrangement |
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Peripheral blood finding to make diaagnosis of AML?
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leucocytosis with blasts + anemia, thrombocytopenia in 90%
10%: pancytopenia (or normal leukocyte count with blasts) |
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AML – risk assesment is based on what?
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Chromosomal abberations and age.
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General strategy and stratification of treatment of AML when: >65 yo
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Palliative approach
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General strategy and stratification of treatment of AML when: <65 yo
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Intensive chemo with curative intent +- BMT
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General strategy and stratification of treatment of AML when: Acute promyelocytic leukemia (APL)
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ATRA + chemotherapy
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Overal survival (OS) in AML?
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40% in 5 years
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Epidemiology, etiology of ALL
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Incidence: 1,1 – 1,4/100 000
Double peak incidence: 4 years and 50-80 Etiology: not known Risks: Inherited chromosomal aberrations: +21, |
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T- ALL involves more frequently?
B-ALL involves more frequently? |
T- ALL involves more frequently mediastinal lymph nodes
B- ALL: spleen, liver |
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Patophysiology of ALL
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ALL is derived from morphologically immature precursors of lymphocytes
Primarily involves bone marrow Infiltrates: lymph nodes, spleen, liver, testicules, other parenchymatous orgáns, CNS. T- ALL involves more frequently mediastinal lymph nodes B- ALL: spleen, liver |
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Cytogenetics ALL
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t(9,22) = Ph chromosome, other: t(4;11), t(8;21), t(2;8), t(8;14)
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ALL: classification. acc to FAB
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L1-L3
Does not have influence of the mangement of ALL |
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ALL – making diagnosis: Blood
Bone marrow smear |
Blood counts: leukocytosis + blasts >20%, leukopenia, anemia, thrombocytopenia
Bone marrow smear: blasts >20%, PAS positivity |
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What is Imatinib mesylate (Glivec®)?
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first specific TKI (TyrosineKnase Inhibitor) of bcr/abl
mechanism: occupation of the binding site for ATP first significant breakpoint in the CML management: |
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Myeloprolipherative diseases (MPD):
Common signes? |
Common signes: proliferation 1-3 cell lines with excess in peripheral blood, extramedullary haemopoiesis, bone marrow fibrosis
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Myeloprolipherative diseases (4)
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Chronic myeloid leukemia (CML)
Polycythaemia Vera (PV) Essential thrombocytopenia (ET) Primary myelofibrosis (MF) |
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Which translocation os super important when it comes to MPD?
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Philadelphia!!!
(BCR-abl |
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Chronic myeloid leukemia (CML) definition:
Epidemiology, risk factor, pathophys? |
Definition: myeloprolipherative clonal disease derived from a stem cell, bcr/abl rearrangement involved
Epidemiology: incidence 1/100 000 Etiology: unknown Risk factors: radiation Pathophysiology: gene rearrangment bcr, abl bcr/abl – tyrosinkinase. Cytogenetic marker: t(9;22) = Ph chromosome. |
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CML pathophys:
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Pathophysiology: gene rearrangment bcr, abl bcr/abl – tyrosinkinase. Cytogenetic marker: t(9;22) = Ph chromosome.
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What is the ccourse of CML? What happens during the phases?
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Chronic phase: 50% patients diagnosed incidentialy: sweating, weight loss, pruritus, left hypochondrium pressure
Acceleration phase: symptoms stressed, treatment with decreased effect (need for increase effect) Blastic phase: anaemic syndrome, infection, haemorhagia, left hypochondrial tension – splenomegaly |
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Diagnosis of CML, blood in different phases?
+ bonemarrow histo |
Blood counts:
Chronic phase: leukocytosis with left shift to myeloblasts Acceleration phase: Number of blasts in peripheral blood or bone marrow: 10-30%, eosinophils and basophils: > 20% Blastic phase: blasts >30%, blasts and promyelocytes > 50% Bone marrow - histology: different degree of fibrosis |
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What is the risk assement of CML called?
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Hasford's index.
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Treatment of CML?
How does it work? |
Imatinib mesylate (Glivec®)
first specific inhibitor of tyrosinkinase bcr/abl (TKI) mode of action: occupies binding site ATP standard dose: 400mg/D p.o. 90,3% of patients survive after 54 months of therapy Tolerance: very good Side effects: swellings, rush, neutropenia |
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When can there be resistant to Imatinib (in CML treatment)
What do you do then? |
When mutation of BCR-ABL.
Give Nilotinib (Obtained by crystalic projecting of imatinib ) |
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What is Dasatinib?
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multi target“ kinase inhibitor (Bcr-Abl, SRC, TEC, PDGFR, kit etc)
In CML treatment But is not active against some mutations. |
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Polycythaemia vera (PV)
incidence Median age etiology Definition Pathophys |
Incidence: 0,5 – 0,8/100 000
Median: 60 years Etiology: unknown in most cases (some: ionizing radiation) Definition: myeloprolipherative clonal disease derived from a stem cell with major erythrocyte prolipheration Patophysiology: > 25% erythrocyte mass, erythrocytosis, hyperviscosity, hyperuricaemia, trend to vessel complications |
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What must be done for PV diagnosis?
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1. exclude secondary or relative erythrocytosis
2. Exclude othe MPDs (if Jak-2 is + then it is not PV) |
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PV treatment
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Blood draw
if not work:Litalir (in older pat) All pat will get anti aggregation (aspirin) |
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Essential thrombocythaemia (ET)
Incidence Definition Blood Symptoms acc to blood count? |
Incidence: 0,1/100000
In majority clonal disease with accelerated proliferation of megakaryocyte line Peripheral blood count: PLT > 600 x109/l, slight leukocytosis with a left shift. Blood counts: 1. Bleeding (PLT > 1500 x109/l), 2. Thrombosis (PLT < 1500 x109/l). Thrombosis in atypical sites: v. jugularis, v. portae etc. |
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Treatment of ET
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Hydroxyurea (Litalir, as in PV) in men, women after fertile age
Interferon - (3MU 3 x in a week) in women in fertile age Anagrelide |
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Definition of myeloma?
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Definition: abnormal proliferation and accummulation of plasma cells producing one type of paraproteins . Clinical course has typical picture
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Multiple myeloma: epidemiology
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Approximately 1% of all cancers
second most prevalent haematological cancer (After lymphomas) Median age at diagnosis: 71 years |
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Pathogenesis of MM
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MM arises from a B cell of the normal germinal centre. Initially, MM is confined to the bone marrow, but tumours can acquire the ability to grow outside the bone marrow
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Bone marrow pathophysiology in MM
Compare Osteoblast and osteoclast activity. |
In normal bone, osteoblast and osteoclast function is balanced by the actions of RANKL and OPG
In MM, RANKL is increased, OPG is decreased, resulting in increased osteoclast activity |
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In monoclonal gammopathy of undetermined significance (MGUS), How are the proteins, clonal cells, others?
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In monoclonal gammopathy of undetermined significance (MGUS), the monoclonal protein is <30 g/l with <10% bone marrow clonal cells and no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis
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Which is the most common serum onoclonal antibody in MM?
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IgGkappa
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Diagnosis and investigation
of MM? |
Patients typically present with bone pain, renal impairment, anemia, or a combination of these
Myeloma should also be considered in patients with unexplained backache, loss of height, or radiologic evidence of osteoporosis, recurrent bacterial infection |
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What staging sytem (not the international one) is used for MM? What is it based on?
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In the Durie-Salmon Staging System, the clinical stage of disease (Stage I, II, or III) is based on several measurements, including levels of M protein, the number of bone lesions, haemoglobin values, and serum calcium levels. Stages are divided further according to kidney function, which is determined by serum creatinine levels (classified as A or B)
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What is the internatioanl staging system of MM based on?
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A combination of serum b2-microglobulin and serum albumin provided a simple, powerful, and reproducible 3-stage classification
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Treatment.. Do not understand it.
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Treatment.. Do not understand it.
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