Leukemia Maturation of Myeloid Cells Dr. Rania Alhady

Leukemia Dr. Rania Alhady Definition: Classification of leukemia: Leukemias are a group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood. • Abnormal cells cause symptoms because of: (i) bone marrow failure (i.e. anemia, neutropenia, thrombocytopenia) and (ii) infiltration of organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin or testes). Classification of leukemia: 1- Acute Leukemia: Acute lymphoblastic leukemia: L1 – L3. Acute myeloid leukemia: M0 – M7. 2- Chronic Leukemia: Chronic lymphocytic leukemia. Chronic myeloid leukemia. Dr. Rania Alhady

Acute leukemia Acute Leukemia: Dr. Rania Alhady Definition: Etiology: Clonal malignant disorders characterized by: Uncontrolled proliferation of abnormal blast cells in bone marrow, and Impaired production of normal blood cells. Blast cells infiltrate peripheral blood and bone marrow. Blast cells in bone marrow must be > 30% to diagnose acute leukemia. Etiology: 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. Dr. Rania Alhady

Acute leukemia Dr. Rania Alhady Results: Classification: * Chromosomal abnormality: Imbalance between oncogene and anti-oncogene. * Blast cells: Uncontrolled proliferation of this clone results in: 1- Arrest of cellular differentiation. 2- Reduced apoptosis. 3- Inhibition of normal marrow elements. Classification: Acute leukemias are classified according to the type of blast cells into: ALL: Childhood leukemia. AML: Adulthood leukemia. Acute leukemias are fatal if not treated. However, acute leukemias are easier to treat than chronic leukemias. Dr. Rania Alhady

Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia (ALL): It is the result of clonal proliferation of lymphoid progenitor cells originating in the marrow. Incidence: Under 10 – 15 years (Childhood onset) Can be either B-cell ALL or T-cell ALL. • B-cell ALL or T-cell ALL can be further classified into subtypes according to the moderate splenomegaly, hepatomegaly and meningeal syndrome. Classification of acute lymphoblastic leukemia (ALL) according to the French-American-British (FAB) groups Dr. Rania Alhady

Acute Lymphoblastic Leukemia Clinical features: 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: L.N. enlargement. Hepatomegaly. More common with ALL than AML. Splenomegaly. 3- Organ infiltration: A- Bony infiltration. B- Testicular infiltration. C- C.N.S. infiltration. 4- Fever. Dr. Rania Alhady

Acute Lymphoblastic Leukemia Investigations: 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 B. BM Biopsy: Indicated in: If aspirate is: a- Difficult. b- Hypercellular Follow up. Dr. Rania Alhady

Acute Lymphoblastic Leukemia FAB Classification: L3 L2 L1 Homogenous Heterogenous in size and shape Cell population Large Small & Large Small Cell Size ↓ ↑ N/C ratio Prominent Prominent (1 - 2) Inconspicuous Nucleoli Basophilic with vaculations Larger Scanty Cytoplasm 1% 14% 85% Child Age 9% 60% 31% Adult Dr. Rania Alhad y

Acute Lymphoblastic Leukemia Morphological classification of ALL L1 L2 L3 (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. Dr. Rania Alhady

Acute Lymphoblastic Leukemia 3- Immunophenotyping: Antigen present in the cell membrane A- Myeloid markers: -ve CD13, CD33 B- Pan B markers: +ve CD19, CD20, CD22 C- Pan T markers: +ve CD2, CD5, CD7 4- Cytogenetics: • Philadelphia chromosome translocation t(9; 22): may occur and results in poor prognosis. 5- Cytochemistry: Chemical activity of the cell. Myeloperoxidas, Sudan Black B, Non-specific estrase: -ve Acid phosphatase: +ve in T-ALL PAS (periodic acid shiff): +ve Dr. Rania Alhady

Acute Lymphoblastic Leukemia 6- Radiology: CXR: mediastinal mass (T-cell ALL) Osteopenia or lytic lesion 50% of patients with ALL.(itractable pain). Prognosis of ALL: Bad prognosis in: WBCs: ↑ > 20.000 Sex: boys due to testicular involvement. Serum Ig ↓ (also ↑ incidence of T-ALL) L2 & L3 morphology. Organomegaly Cytogenetic abnormalities T-ALL Dr. Rania Alhady

Acute Myeloid Leukemia Acute Myeloid Leukemia (AML): Definition: Clonal proliferation of myeloid precursor cells with reduced capacity to differentiate into more mature cellular elements. Results in accumulation of leukemic forms in bone marrow, peripheral blood, and other tissues. Leads to reduction in RBCs, platelets, PMNs. It occurs in several morphologic variants; each one has a characteristic clinical & lab. features (M0 – M7) Dr. Rania Alhady

Acute Myeloid Leukemia Incidence: AML is the most common leukemia in neonates. 80% of AML is in adults. 20% of AML is in children. Diagnosis: Clinical Picture: Anemia  weakness and easy fatigue Neutropenia  infections Thrombocytopenia  gingival bleeding, ecchymoses, epistaxis, menorrhagia Anorexia, weight loss, fever. Organomegaly: HSM in 1/3 of patients. Lymphadenopathy is uncommon except in monocytic variants. Dr. Rania Alhady

Acute Myeloid Leukemia B. Laboratory diagnosis: Bone Marrow Exam: Aspiration and biopsy * Morphologic classification using cytochemistry and immunophenotyping Cytochemistry: Peroxidase: +ve Sudan black: +ve Specific esterase: +ve Immunophenotyping: Pan myeloid markers: +ve CD13, CD33 * Cytogenetic analysis * Evaluation for presence of significant fibrosis, presence of granulomata Dr. Rania Alhady

Acute Myeloid Leukemia Diagnosis requires all of the following diagnostic components: Documentation of bone marrow infiltration Myeloid origin of the leukemic cells FAB/WHO classification of the leukemia FAB Classifications M0: minimally differentiated M1: without maturation M2: with maturation. M3: promyelocytic. M4: myelomonocytic. M5: monoblastic M6: erythroleukemia M7: megakaryoblastic. Dr. Rania Alhady

Acute Myeloid Leukemia Dr. Rania Alhady

Acute Myeloid leukemia Dr. Rania Alhady