Leukemia

Leukemia

Dr. Rania Alhady 1

Maturation of Myeloid Cells

* Definition of leukemia: Leukemia is malignant proliferation of hematopoietic cells in the bone marrow followed by blood dissemination and soft tissue infiltration. • Leukemic cells produce symptoms because of:(i) Bone marrow failure (i.e. anemia, neutropenia, thrombocytopenia) and(ii) Infiltration of body organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin or testes).

* Classification of leukemia:1. Acute Leukemia:• Acute lymphoblastic leukemia (ALL): L1 – L3.• Acute myeloblastic leukemia: (AML): M0 – M7.

2. Chronic Leukemia: Chronic lymphocytic leukemia (CLL). Chronic myelocytic leukemia (CML).

Leukemia

Dr. Rania Alhady 2

* Etiology of leukemia:

1. Congenital disorder: Down syndrome, Immunodeficiency syndrome.

2. Ionizing radiation: X-ray, radiotherapy.

3. Chemicals: (alkylating agent, Benzene).

4. Viruses: Human T-lymphocyte leukemia virus (HTLV1), Herpes virus, EBV.

Leukemia

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Acute Leukemia- Uncontrolled proliferation of leukemic (blast cells) in bone marrow, and followed by

infiltration of peripheral blood and soft tissues (lymph nodes, spleen, liver, meninges,

gum……).

N.B:

• Blast cells in bone marrow must be > 30% to diagnose acute leukemia.

• Acute leukemias are fatal if not treated.

• However, acute leukemias are easier to treat than chronic leukemias.

Acute leukemia

Dr. Rania Alhady 4

* Classification of acute leukemia:

- Acute leukemias are classified according to the type of blast cells into:

1. Acute lymphoblastic leukemia (ALL): Childhood leukemia.

2. Acute myeloblastic leukemia (AML): Adulthood leukemia.

Acute leukemia

Dr. Rania Alhady 5

Acute Lymphoblastic Leukemia (ALL):• It is the result of clonal proliferation of lymphoid progenitor cells (B or T lymphoblast)

originating in the bone marrow.

• About 85% of ALL are of B type, occurs in children, characterized by extensive bone marrow

infiltration and variable peripheral blood involvement.

• About 15% of ALL are of T type, occurs in adolescents characterized by extensive thymic

gland infiltration and marked peripheral blood involvement.

• Malignant B and T lymphoblasts are also morphologically indistinguishable, and

subclassification of ALL is thus dependent on immunophenotyping according to the French-

American-British (FAB) classification system into L1, L2 and L3.

Acute Lymphoblastic Leukemia

Dr. Rania Alhady 6

* Clinical features of ALL:1- Bone marrow failure: - RBCs → Anemia: pallor, lethargy, malaise and dyspnea.- Leukocytes → neutropenia: fever, malaise, features of mouth, skin, respiratory infections.- Platelets → throbombocytopenia: spontaneous bruises, pupura, bleeding gums.2- Tissue infiltration:

A. L.N. enlargement.B. Hepatomegaly. More common with ALL than AML.C. Splenomegaly.

3- Organ infiltration:A- Bony infiltration.B- Testicular infiltration.C- C.N.S. infiltration.

4- Fever.

Acute Lymphoblastic Leukemia

Dr. Rania Alhady 7

* Investigations of ALL:1. CBC:

60% of patients have an elevated ↑↑ WBCs. RBCs: ↓ Hb Platelets: ↓ Neutrpenia 90% have lymphoblasts in the peripheral blood film.

2. Bone marrow:BM Aspirate: Hypercellular BM All normal marrow elements are depressed and replaced by abnormal blasts. 30% or more of all nucleated cells are blast

Acute Lymphoblastic Leukemia

Dr. Rania Alhady 8

ALL: Lymphoblasts have condensed chromatin, inconspicuous nucleoli, and scant agranular

cytoplasm 9

Morphological classification of ALL

L1 L2 L3

Acute Lymphoblastic Leukemia

Dr. Rania Alhady 10

(a) L1 subtype-blasts show scanty cytoplasm without granules.(b) L2 subtype-blasts are larger and heterogeneous with more abundant cytoplasm.(c) L3 subtype-blasts are deeply basophilic with cytoplasmic vacuolation.

3- Immunophenotyping:- Detection of the Antigen present in the cell membrane of the blast cells.

A- Myeloid markers: -ve CD13, CD33

B- Pan B markers: +ve CD19, CD20.

C- Pan T markers: +ve CD2, CD5, CD7

4- Cytogenetics: • Philadelphia chromosome translocation t (9; 22): may occur and results

in poor prognosis.

Acute Lymphoblastic Leukemia

Dr. Rania Alhady 11

Prognosis of ALL:Bad prognosis in:1) WBCs count: ↑ > 20.0002) Sex: boys due to testicular involvement.3) L2 & L3 morphology.4) Organomegaly.5) Cytogenetic abnormalities (philadelphia chromosome).6) Pre-T ALL

Acute Lymphoblastic Leukemia

Dr. Rania Alhady 12

Acute Myeloid Leukemia (AML)

* Definition:

- Malignant proliferation of myeloid precursor cells with reduced capacity to

differentiate into more mature cellular elements.

* Incidence:

Acute myelogenous leukemias affect primarily adults, peaking in incidence between

the ages of 15 and 39 years, but are also observed in older adults and children.

Acute Myeloid Leukemia

Dr. Rania Alhady 13

* Diagnosis:

A. Clinical Picture:

• Anemia weakness and easy fatigue

• Neutropenia infections

• Thrombocytopenia gingival bleeding, ecchymoses, epistaxis, menorrhagia

• Anorexia, weight loss, fever.

• Organomegaly:

- Hepatosplenomegaly (HSM): in 1/3 of patients.

- Lymphadenopathy: is uncommon except in monocytic variants.

Acute Myeloid Leukemia

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B. Laboratory diagnosis:1. Bone Marrow Exam: The diagnosis of AML is based on the detection of myeloid blasts

which make up more than 20% of the cells in the bone marrow. Myeloblasts have delicate nuclear chromatin, two to four

nucleoli, and more voluminous cytoplasm than lymphoblasts.

2. Immunophenotyping: +ve Pan myeloid markers: CD13, CD33

Acute Myeloid Leukemia

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* FAB Classification of AML:AML is divided into eight (M0 to M7) categories. This scheme takes into account both the degree of maturation (M0 to M3) and the lineage of the leukemic blasts (M4 to M7).

M0: minimally differentiated AML.M1: without maturation AML.M2: with maturation AML.M3: promyelocytic AML.M4: myelomonocytic AML.M5: monocytic AML.M6: erythroleukemia AML.M7: megakaryoblastic AML.

Acute Myeloid Leukemia

Dr. Rania Alhady 16

* Prognosis of AML:- AML is a difficult disease to treat. Approximately 60%

of the patients achieve complete remission with chemotherapy.

Acute Myeloid Leukemia

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