Leukemia-I (Acute Leukemia) PDF

# جامعة المعرفة ALMAAREFA UNIVERSITY ## Leukemia-l 1/19/2025 ## Intended learning objectives - Define leukemia. - Describe types of leukemia's. - Predisposing factors. - Describe acute lymphoblastic leukemia. - Describe acute myeloblastic leukemia. ## Maturation of hematopoietic Cells - A diagram...

# جامعة المعرفة ALMAAREFA UNIVERSITY ## Leukemia-l 1/19/2025 ## Intended learning objectives - Define leukemia. - Describe types of leukemia's. - Predisposing factors. - Describe acute lymphoblastic leukemia. - Describe acute myeloblastic leukemia. ## Maturation of hematopoietic Cells - A diagram showing the maturation process of hematopoietic cells from myeloid stem cell to mature cells like basophil, eosinophil, neutrophil, monocyte, and lymphocyte. - A diagram showing the maturation process of hematopoietic cells from lymphoid stem cell to mature cells like lymphocyte. ## Definition - Malignant proliferation of hematopoietic cells in the bone marrow followed by blood dissemination and soft tissue infiltration. - Leukemia produces symptoms because of: - Bone marrow failure (i.e. anemia, neutropenia, thrombocytopenia) - Infiltration of body organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin or testes). ## Classification - **Acute Leukemia** - Acute lymphoblastic leukemia (ALL): L1 - L3. - Acute myeloblastic leukemia: (AML): М0 - М7. - **Chronic Leukemia** - Chronic lymphocytic leukemia (CLL). - Chronic myelocytic leukemia (CML). ## Predisposing factors 1. Congenital disorder: Down syndrome, Klinefelter's syndrome. 2. Immunodeficiency syndrome. 3. Ionizing radiation: - Nuclear fall-out - Therapeutic irradiation- used in treatment of Hodgkin lymphoma etc. - Diagnostic X-rays: intra-uterine fetal exposure to low-dose radiation (for X-ray pelvimetry) increases occurrence of acute leukemia., 4. Chemical agents: - Alkylating agents used in chemotherapy, - Occupational exposure to benzene. - Drugs like etoposide. 5. Smoking 6. Viruses: Human T-lymphotropic virus type-1 (HTLV-1), Herpes virus, EBV. ## Acute Leukemia ### Definition - Uncontrolled proliferation of blast cells (precursor cells) in bone marrow, and followed by infiltration of peripheral blood and soft tissues (lymph nodes, spleen, liver, meninges, gum......). ### Important features - Blast cells in bone marrow must be > 20% to diagnose acute leukemia. - Acute leukemias are fatal if not treated. - However, acute leukemias are easier to treat than chronic leukemias. ### Classification - Acute leukemia's are classified according to the type of blast cells into: - Acute lymphoblastic leukemia (ALL): Childhood leukemia. - Acute myeloblastic leukemia (AML): Adulthood leukemia. ## Acute Lymphoblastic Leukemia (ALL) ### Definition - Uncontrolled proliferation of B or T lymphoblast's (lymphoid precursor cells) in bone marrow, and followed by infiltration of peripheral blood and soft tissues (lymph nodes, spleen, liver, meninges, gum......). ### Epidemiology - Most common malignant disease in children - Peak incidence: 2-5 years - ♂ > ♀ - About 85% of ALL are of B type, occurs in children. - About 15% of ALL are of T type, occurs in adolescents. ### Clinical features - **Bone marrow failure** - RBCs → Anemia: pallor, lethargy, malaise and dyspnea. - Leukocytes → neutropenia: fever, malaise, features of mouth, skin, respiratory infections. - Platelets → thrombocytopenia: spontaneous bruises, pupura, bleeding gums. - **Tissue infiltration** - L.N. enlargement. - Hepatomegaly - Splenomegaly. - Bony infiltration. - Testicular infiltration. - C.N.S. infiltration. - Fever, Fatigue, Bone pain. ### Investigations - **Complete blood count (CBC):** - WBCs: Leucocytosis (may reach > 100,000/mm3). - (but maybe normal or Low WBCs count) - RBCs: anaemia - Platelets: thrombocytopenia. - **Peripheral smear:** - Leukocytosis and lymphoblast's in the peripheral blood smear. - **Bone marrow examination:** - Hypercellular BM. - > 20% lymphoblasts. - All normal marrow elements are depressed and replaced by abnormal lymphoblasts. ### Morphology of Lymphoblast's - Size- 10-20 μm. - Cytoplasm- scanty. - Auer Rod- absent. - Nuclear chromatin- coarse - Nucleoli- indistinct. ### Cytochemistry - Terminal deoxynucleotidyl transferase" (TdT)- Positive - Periodic acid schiff's (PAS) reaction-often positive ### Immunophenotyping - By Flow cytometry method. - Detection of the Antigen present in the cell membrane of the blast cells. - B - Lymphoid markers: CD19, CD20, CD22, (& CD10). - T - Lymphoid markers: CD2, CD3, CD5, CD7. ### Cytogenetic analysis: - Prognostic and therapeutic implications. - Hyperdiploidy (>50 chromosome) - Associated with good prognosis. - Philadelphia chromosome, t(9; 22): may occur and results in poor prognosis (present in ~ 20-30% of adults with ALL but only ~ 5% of children with ALL) ### Other investigations - Lumbar puncture-in CNS involvement. - Testicular biopsy- testis is a frequent site of relapse. - X-ray chest- mediastinal widening in T-ALL. ### Prognosis - With aggressive chemotherapy about 95% of children obtain a complete remission, and 75% to 85% are cured. ### Factors associated with a worse prognosis - Age < 2 or > 10 years - CNS involvement - WBCs count greater than 50,000/mm3. - Presence of t(9;22) (the Philadelphia chromosome). ### Favorable prognostic markers - Age of 2 to 10 years, - Low white cell count, (leukocyte count < 50,000/mm3) - Hyperploidy, - t(12;21) ## Acute Myeloblastic Leukemia (AML) ### Definition - Malignant proliferation of myeloid precursor cells (myeloblasts) with reduced capacity to differentiate into more mature cellular elements. ### Epidemiology - Occurs at all ages. - Incidence peaks after 60 years of age. ### FAB Classification - 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: AML, without maturation. - M1: AML with minimal granulocyte maturation. - M2: AML with granulocyte maturation-most common subtype. - M3: Acute promyelocytic leukemia (APL). t(15,17) - M4: Acute myelomonocytic leukemia. - M5: Acute monocytic leukemia. - M6: Acute erythroid leukemia. - M7: Acute megakaryoblastic leukemia. ### Clinical features - **Bone marrow failure.** - RBCs → Anemia: pallor, lethargy, malaise and dyspnea. - Leukocytes → neutropenia: fever, malaise, features of mouth, skin, respiratory infections. - Platelets → thrombocytopenia: spontaneous bruises, pupura, bleeding gums. - **Soft tissue infiltration.** - Sometimes it may present as localized soft-tissue mass known as "chloroma' or myeloid sarcoma' ### Investigations - **Complete blood count (CBC):** - Leucocytosis (> 1,00,000/cmm). - RBCs: anaemia - Platelets: thrombocytopenia. - **Peripheral smear:** - Leukocytosis and myeloblast's in the peripheral blood smear. - **Bone marrow examination:** - Hypercellular BM. - > 20% myeloblasts. - All normal marrow elements are depressed and replaced by abnormal myeloblasts. ### Morphology of Myeloblast's - Size- 20 μm. - Cytoplasm- moderate. - Auer Rod- present. - Nuclear chromatin- fine. - Nucleoli- prominent, 1-4. ### Cytochemistry - Myeloperoxidase (MPO) - granular positivity in AML. ### Immunophenotyping - By Flow cytometry method. - Myeloid markers: CD13, CD33, ### Cytogenetic analysis - Cytogenetic analysis has a central role in the WHO classification of AML. - Common chromosomal abnormalities: - t(8;21), inv(16), and - t(15:17), especially in acute promyelocytic leukemia (M3 AML) ### Prognosis - Difficult disease to treat. - 60% of patients achieve complete remission with chemotherapy. - Only 15% to 30% remain free of disease for 5 years. ## REFERENCES - Robbins Basic Pathology 10th edition, 2017 (Kumar, Abbas, Aster) - AMBOSS LINK: https://next.amboss.com/us/article/iT0Jq2?q=acute+leukemia#Zb0896ded63580d157d92e84db4f0b064 ## THANK YOU ## H.W. | | ALL | AML | |:-----|:------|:-------| | Age | | | | Cell of origin | | | | Classification | | | | Most common type | | | | Clinical features | | | | CBC | | | | Peripheral smear | | | | Bone marrow morphology | | | | Cytochemistry | | | | Immunophenotyping | | | | Cytogenetics | | | | Prognosis | | | ## Case 1 - A 5-year-old boy is brought to the physician by his parents because of a 6-week history of increased tiredness, irritability, and worsening leg pain. His parents report that he has been reluctant to walk recently because of the pain in his legs. Temperature is 38.1°C (100.6°F); other vital signs are within normal limits. Examination shows conjunctival pallor and diffuse petechiae. His hemoglobin concentration is 8.9 g/dL, leukocyte count is 45,750/mm3, and platelet count is 25,000/mm3. A bone marrow aspiration shows numerous immature cells that stain positive for CD10, CD19, and terminal deoxynucleotidyl transferase (TdT). **Which of the following translocations is associated with a favorable prognosis for this patient's condition?** - A. t(12;21) - B. t(15;17) - C. t(8;14) - D. t(14;18) - E. t(9;22) ## Case 2 - A 67-year-old man comes to the physician because of a 2-month history of generalized fatigue. On examination, he appears pale. He also has multiple pinpoint, red, nonblanching spots on his extremities. His spleen is significantly enlarged. Laboratory studies show a hemoglobin concentration of 8.3 g/dL, a leukocyte count of 81,000/mm3, and a platelet count of 35,600/mm3. A peripheral blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. **What is the most likely diagnosis?**