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Acute leukemias

Leukemia
Initial definition: Highly increased number of WBC

Present definition: Bone marrow neoplastic


disease (even without leukocytosis)

Why WBC :
Bone marrow increased production
Increased dismission into circulation
Reduced apoptosis
Types of leukemia

ACUTE
Myeloid
Lymphoid

CHRONIC
Myelogenous
Limphocytic
Leukemia: pathogenesis
The disease is clonal, i.e.,originates from a
single abnormal cell

Multiple step theory

Several steps are somatic mutations


occurring in a hematological stem cell.
Some step may be hereditary (mutation in a
germinal cell)
Leukemogenic mutations

Which gene:
Oncogene activation
Oncosuppressor gene inactivation

Type of mutations:
Single base mutation
Deletions, frameshift
Duplications
Translocations (hybrid genes)
Examples of hybrid genes

Philadelphia chromosome in Chronic


Myelogenous Leukemia :
t (9;22) brc/abl

Acute Promyelocytic Leukemia :


t (15;17) pml/rar
Acute leukemias
10% of all human tumors

Incidence: 5 7 new case/year/100.000

Age peaks:
ALL 3 14 years
AML 55 75 years
Acute leukemias: events

Mutated cell high proliferation rate


Bone marrow invasion
Normal hematopoiesis suppressed
Maturation arrest
Acute leukemias: presentation

Skin and mucous hemorrage

Stomatitis

Liver/spleen/lymph node enlargment

Severe infections
Acute leukemias: diagnosis
Full blood count:
WBC usually , Hb , platelet
Differential: presence of blast cells
Bone marrow aspirate
Blast substitution
Additional studies:
Cytogenetics
Molecular biology tests
LDH and Uric acid often elevated
Acute leukemias: classifications
FAB: ALL 3 types (L1, L2, L3)
AML 8 types (M0 to M7)

IMMUNOLOGICAL
ALL: B or T

CYTOGENETIC
MOLECULAR
ALL subtypes
L1: small cells, childhood
L2: mixed small and large cells, adults
L3: large cells, Burkitts-like

B-cells: more frequent, better prognosis in


childhood
T-cells: rare, tend to relapse. Often have
mediastinal mass and very high WBC
AML subtypes (FAB)

M0 undifferentiated
M1 initial myeloid differentiation
M2 overt myeloid phenotype
M3 promyelocytic
M4 myelomonocytic
M5 monoblastic/monocytic
M6 erythroleukemia
M7 megakaryocytic
Acute leukemias: flow cytometry
Very helpful in clarifying unusual subtypes
Can be used to detect what remains after
an effective treatment (minimal residual
disease)
Myeloid antigens: CD13, CD33, CD14,
MPO, Glycophorin, etc.
Lymphoid antigens: CD2, CD3, CD7, CD10,
CD19, TdT, SmIg, etc
ALL : treatment strategy

Children: Chemotherapy only, prolonged


for about 3 years.
Be aware of meningeal involvement: intrathecal
prophylaxis needed

Adults : Chemotherapy, + BMT if possible


AML: treatment strategy
1. Induction treatment:
combination of 2 - 3 cytotoxic drugs
(daunorubicin, etoposide, Ara-C: 3+5+7)
2. Consolidation:
(3+3+5)
3. Bone marrow transplant, if possible:
Allogeneic
Autologous
M3 AML : peculiarities
Atypical promyelocytes
t(15:17) in all cases
PML/RARalfa hybrid gene
Very often severe coagulation inpairment
Retinoic Acid and Arsenic very effective
Best prognosis
AML: frequent cytogenetic findings

t(8;21) M2, young adults


t(15;17) M3
inv(16) M4Eos
+8 M2, M4, M5
t(9:22)
Chromosome 5 or 7 abnormalities
Acute leukemias: supportive therapy

RBC transfusion
Platelet transfusion
Antibiotics
Antifungi
Antiviral

Protected ward

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