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

Question 1

Leukemias

Answer 1

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

Question 2

Acute Leukemias

Answer 2

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

Question 3

Pathogenesis of Acute Leukemia

Answer 3

• 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

Question 4

Definition of Acute Leukemia

Answer 4

• 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)

Question 5

Acute Promyelocytic Leukemia (M3)

Answer 5

Usually see a 15:17 translocation and AUER RODS

Question 6

t(8;21)

Answer 6

• 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

Question 7

Treatment of AML

Answer 7

• 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

Question 8

Differentiation of ALL from AML

Answer 8

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

Question 9

Genetics and outcome of ALL

Answer 9

-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)
-

Question 10

Treatment of ALL

Answer 10

-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

Question 11

CONCLUSION

Answer 11

• 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