3.25 GOORHA Acute Leukemia-Biology, Clinical feats. and Therapy Flashcards Preview

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Flashcards in 3.25 GOORHA Acute Leukemia-Biology, Clinical feats. and Therapy Deck (11):
1

Leukemias

Group of heterogenous disorders characterized by the accumulation of malignant white cells in the BM and blood.
-These abnormal cells cause morbidy and mortality of:
--BM failure: anemia, neutropenia, thrombocytopenia
--Infiltration of organs: liver, spleen, lymph nodes, meninges, brain skin or testes

2

Acute Leukemias

ALL: most common in children (3-7)
AML: 15-59 increasing incidence with age
--Primary AML (de novo)
--Secondary AML (develops from MDS or other hematatological malig) is much more difficult to treat

3

Pathogenesis of Acute Leukemia

-Aggressive disease
-Malignant transformation occurs in hematopoetic stem cells or early progenitors
-Genetic damage leads to: (1) increased rate of proliferation (2) reduced apoptosis (3) block in cellular differeation
-Collectively result in early BM hematopoietic cells known as BLAST CELLS

4

Definition of Acute Leukemia

-Generally >20% of blast cells in the blood or BM
-Can diagnose with <20% if sp cytogenetic or molecular genetic mutation are present
-differ between AML and ALL usually with IMMUNOPHENOTYPING
--Myeloid: MPO, CD33, CD13, HLA-DR
--Lymphoid: TdT, CD10, CD19, CD20
-Also morphologically AML will have AUER RODS (Acute Promyelocytic leukemia/M3)

5

Acute Promyelocytic Leukemia (M3)

Usually see a 15:17 translocation and AUER RODS

6

t(8;21)

-AML (M2)
-ETO/AML1
-CD13+, CD33+ (maturing myeloid)
-CD34+ (blasts)
-Will see AUER RODS
-Will also see more blasts in BM than mature cells (by a lot), Myeloid differentiation is inhibited

7

Treatment of AML

-Remission induction therapy: intensive therapy to achieve a complete response (absence of detectable leukemia cells)
-Post-remission therapy/consolidation therapy: 3 to 4 courses of intensive short-couse therapy
-Some pts: maintenance therapy or allogenic BM transplant
-Azacitidine: shows better outcome with older patients

8

Differentiation of ALL from AML

-Morphologic: presence of AUER RODS =AML
-Immunological markers:
--Myeloid antigens: MPO, CD33, CD13, HLA-DR
--Lymphoid antigens: TdT, CD10, CD19, CD20

9

Genetics and outcome of ALL

-MLL-AF4 & BCR-ABL: poor outcome (kids and adults) and overall more common in adults
-E2A-PBX and TEL-AML ass with good outcome and seen mostly in kids (rarely in adults)
-

10

Treatment of ALL

-Allopurinol to counter tumor lysis syndrome
-CNS prophylaxis: intrathecal chemo admin
-70-85% cure rate in children, worse prognosis in adults (genetics?)
-INduction: VCR, L-ASP, DEX or PRED
+/-Daunorubicin

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CONCLUSION

-Using genetics to gain a better understanding of prognostic variables: beter risk stratification
-Tailored therapy based on genetic abnormalities
-Better strategies for older AML patients
-Trat at specialized centers
-Clinical Trials
-Immunotherapy
-Stem Cell Transplantation