S31 Acute Leukemias Flashcards
CD34 is expressed on
most stem cells
TdT expression defines a
lymphoid lineage
AML is characterized by what immunological markers usually
CD13, CD33, CD117
B-ALL is characterized by what immunological markers
TDT, CD10, CD19, cCD22
T-ALL is characterized by what markers
TdT, CD2, CD3, CD7
AML can occur with what recurrent genetic abnormalities
t(8;21) inv(16) t(15;17)(q22;q12); PML-RARA
AML with recurrent genetic abnormalities and diagnostic criteria
detections of genetic abnormalities means that bone marrow blast cell count does not need to exceed 20% in order to make a diagnosis. have good prognosis.
AML with myelodypslasia-related changes
AML associated with microscopic features of dysplasia in a least 50% of cells in at least two lineages.
Therapy-related myeloid neoplasms (t-AML)
arises in patients who have been previously treated with drugs such as etoposide or alkylating agents commonly exhibit mutations in MLL gene. clinical response usually poor.
AML, not otherwise specified
absence of cryogenic abnormalities and comprises around 30% of all cases. Mutations in NPM! and FLT3 genes r more freq in those with normal cryogenetics
Myeloid sarcoma
rare refers to disease resembles a solid tumor but is composed of myeloid blast cells
Myeloid proliferations related to down’s syndrome
children w/ Down’s syndrome increased risk of acute leukemia two myeloid variants recognized: - transient abnormal myelopoiesis, self-limiting leucocytosis -AML
Mixed phenotype acute leukaemia
express two markers for both myeloid and lymphoid differentiation either on same blast cells or on two different cell populations. poor prognosis.
Clinical features of AML
down marrow failure due to accumulation of malignant cells within marrow infections- frequent profound anaemia and thrombocytopenia promyelocytic variant for AML: bleeding tendency due to thrombocytopenia and disseminated intravascular coagulation (DIC) Tumour cells infiltrate variety of tissues Myelomonocytic (involves a proliferation of CFU-GM myeloblasts and monoblasts) and monocytes subtypes: Gum hypertrophy and infiltration by leukemia cells, skin involvement and CNS disease
Favorable cytogenetics for AML
t(15:17), t(8;21), inv(16), Trisomy 8 No FLT3 mutation Nucleophosmin-1 mutation CEBPa mutation
Unfavorable cytogenetics for AML
11q23 abnormality - MLL gene deletions of chromosome 5 or 7 TP53 mutated Abnormal (3q) t(6;11), (10;11), (9;22) FLT3 internal tandem repeat
AML treatment overview
supportive and specific Induction- determine by age, cytogenetics and performance status CR 66-85% no maintenance CNS treatment - neuro deficit or headache - M4, M5 supportive care Hematopoietic cell transplantation: High risk disease, relapsed disease
AML treatment drugs
most commonly used drugs: cytosine arabinoside and daunorubicin Idarubicin, mitoxantrone ALL-trans retinoid acid (ATRA) and Arsenic trioxide is used in promyelocytic leukemia (presents with bleeding)
Neutropenia
decreased number of circulating neutrophils
Causes of Neutropenia
Drug Toxicity (e.g. chemotherapy with alkylating drugs): damage to stem cells results in decreased production of WBCs, especially neutrophils
Severe infection (e.g., gram-negative sepsis)- Increased movement of neutrophils into tissues results in decreased circulating neutrophils
What can be used a treatment to boost granulocyte production
GM-CSF
G-CSFf
lymphopenia
decreased number of circulating lymphocytes
Lymphopenia is caused by
Immunodeficiency (e.g. DiGeorge syndrome or HIV)
High cortisol state (exogenous corticosteroids, or cushing syndrome): induces apoptosis of lymphocytes
Autoimmune destruction (systemic lupus erythematosus)
Whole Body radiation- lymphocytes are highly sensitive to radiation; lymphopenia is earliest change to emerge after whole body radiation.
