ACUTE LEUKEMIA

Thuvija Darshini Govindev 0902005194

Definition
Malignant transformation of hematopoietic progenitor cells at an early stage of differentiation (blasts), resulting in an accumulation of immature and nonfunctional cells in the bone marrow. These blasts crowd bone marrow and compromise the development of other blood cells.

Types of Acute Leukemia

ALL (acute lymphoblastic leukemia) - Transformed lymphoid blasts - More common in children 2 AML (acute myeloid leukemia) - Transformed myeloid blasts - More common in adult

Acute Lymphoblastic Leukemia

Predominantly childhood disease 2500 cases/yr. 80% of childhood leukemia 1/3 of all childhood deaths whites >non-whites, boys> girls Risk factors-Genetic syndromes, radiation, twin Two major categories: B and T cell lineages

Acute Myeloid Leukemia

It is monoclonal expansion of myeloblast cells. Myeloblast in AML, will have Auer rod. According to FAB classification, there is 8 types of AML; M0 to M7. - The treatment of AML differs to each type. - In order to know the type, you should do cytogenetic analysis and flow cytometry.

Clinical Presentation
Pallor & fatigue (anemia) Bruising, purpura, and bleeding (thrombocytopenia) Fever & Infection (decrease in functional WBCs)

Other Clinical Features

Bone pain Pancytopenia Hyperleukocyticsyndrome (WBC >100K/ul) Hepatosplenomegaly Skin and gum infiltration Central Nervous system involvement

classification
FAB-1976 - (AML) degree of maturation (M0-M3) and the the lineage of the leukemic blasts (M4-M7) - Based on morphology and cytochemistry - (ALL) divided to 3 (L1-L3) WHO -2001 - attempts to define forms of AML according to molecular pathogenesis and outcome. - cytogenetics, immunophenotype& clinical outcome - more objective and more biologically and clinically distinctive

FAB Classification
AML M0-minimally differentiated M1-without maturation M2-with maturation M3-promyelocytic (APL); M3v M4-myelomonocytic; M4eo M5 a-monoblastic b-monocytic differentiated M6-erythroid M7-megakaryoblastic ALL L1 L2 L3

Diagnosis of Acute Leukemia

Blasts make up more than 20% of the bone marrow nucleated cells (Normal blast frequency is <3%)

Diagnostic Techniques
Morphology - Blast cells are large with high nuclear-cytoplasmic ratio. The cytoplasm is relatively basophilic. - Differentiation between myeloblast and lymphoblast is so difficult, unless there is Auer rod which characteristic for myeloblast cells. Cytochemistry - Myeloblast is myeloperoxidase positive. - Monoblast is non-specific esterase positive. Immunophenotyping - Immunohistochemistry - Flow cytometry Cytogenetics FISH

Therapeutic Strategies
Induction Goal:to kill all detectable disease & reach CR Consolidation Goal:to eliminate tumor cells with short-term intensive therapy Maintenance Goal:to continue eradicating any remaining undetectable cells though low doses of Txover a longer period of time.

Prognostic Factors : ALL

Favorable Prognostic Factors: - WBC < 50,000/ul -Age: 2-10 years -Lack of CNS involvement -Features of the leukemic clone including: hyperdiploidy (trisomy 4 and 10), CD10, t(12;21) Unfavorable Prognostic Factors: -WBC >50,000 -Age: <2 or >10 -CNS involvement -Features of the clone including: diploidy or hypodiploidy, lack of CD10, t(1;19), 11q23 (MLL gene), t (8;14), t(9;22)

ALL: Outcome
98% of children reach complete remission 2/3 of these will achieve a long term cure 1/3 relapse, and may go into second remission, however, a majority will die from their disease. AllogeneicBM Txoffers hope for these patients.

AML:Outcome
60% achieve complete remission Only 20% of those patients will have a durable remission The other 80% will relapse in 1-2 years. At relapse, it is harder to achieve responses Bone marrow transplant may improve overall survival

THE ENDTHANK YOU.