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MLAB 1415: Hematology Keri Brophy-Martinez

MLAB 1415: Hematology Keri Brophy-Martinez. Chapter 25: Acute Lymphoblastic Leukemia. Overview. Causes a wide spectrum of syndromes From involvement of bone marrow and peripheral blood( leukemias ) to those that cause masses (lymphomas) in lymphoid organs.

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MLAB 1415: Hematology Keri Brophy-Martinez

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  1. MLAB 1415: HematologyKeri Brophy-Martinez Chapter 25: Acute Lymphoblastic Leukemia

  2. Overview • Causes a wide spectrum of syndromes • From involvement of bone marrow and peripheral blood(leukemias) to those that cause masses (lymphomas) in lymphoid organs. • The cell of origin may involve the common lymphoid progenitor cell OR differentiated progenitors of the T, B or NK cells • T cell malignancies more aggressive, often involve extranodal/extramedullary sites like skin, CNS, mediastinum • Neoplastic B cells secrete monoclonal proteins( IgM,IgG, IgA) inappropriately causing increased viscosity of blood, impairing blood flow

  3. Etiology • Hematologic disorders characterized by malignant neoplastic proliferation and accumulation of immature and dysfunctional hematopoietic cells in the bone marrow. • Abnormality is an acquired genetic mutation within a lymphoid precursor cell that gives rise to a clone of malignant lymphocytes • These “cells” proliferate in an unregulated manner and do not develop into mature cells • Additionally, they have an enhanced ability to self-renew and have a resistance to cell death.

  4. Clinical Findings • Seen in young children • Peak incidence between 2-5 years old • Onset symptoms can be insidious or abrupt • Prognosis with treatment good, if no treatment received, survival very short • Another smaller peak often seen in 60’s • Onset symptoms rapid, fatigue, infections, bruising • Prognosis not good

  5. Clinical Findings • Clinical presentation reflects the degree of marrow failure and the extent of extramedullary disease • Symptoms are related to the replacement of normal marrow elements with leukemic lymphoblasts • Anemia, thrombocytopenia, neutropenia • Fever, weight loss, pallor, fatigue • Petechiae and eechymoses present in half of the patients • Bone pain due to expansion of bm with leukemic cells

  6. Lab Features • WBC variable from 0.1->50 x 109/L • Usually around 10-12 x 109/L • Neutropenia • Lymphoblasts • Normocytic, normochromic anemia • Thrombocytopenia (48-52 x 109/L)

  7. Blood : Bone marrow Bone marrow Peripheral Blood Homogeneity of morphology of lymphoblasts

  8. Blood: Bone Marrow Bone Marrow Peripheral blood Heterogeneous morphology of lymphoblasts

  9. Differentiation between AML and ALL • Age • AML - mainly in adults • ALL - common in children • Blood • AML - anemia, neutropenia, thrombocytopenia, myeloblasts and promyelocytes • ALL - anemia, neutropenia, thrombocytopenia, lymphoblasts and prolymphocytes • Morphology • AML - blasts are medium to large with more cytoplasm which may contain granules, Auer rods, fine nuclear chromatin, distinct nucleoli • ALL - blasts are small to medium with scarce cytoplasm, no granules, fine nuclear chromatin and indistinct nucleoli • Cytochemistry • AML - positive peroxidase and Sudan black, negative TdT • ALL - negative peroxidase and Sudan black, positive TdT

  10. FAB Classification • L1 • Small, uniform lymphoblasts • Scant cytoplasm, indistinct nucleoli, occassional clefting of nucleus, chromatin is clumped • Affects primarily children

  11. FAB Classification: L2 • L2 • Large, pleomorphic lymphoblasts • Abundant cytoplasm, predominant nucleoli, nuclear clefting and indentation • Affects adults

  12. FAB Classification: L3 • L3: Burkitt’s type • Uniform population of large lymphoblasts with deeply basophilic cytoplasm, vacuoles, round to oval nuclei without indentation • Affects adults and children

  13. WHO Classification • Two subgroups • Precursor B and T-cell neoplasms(leukemia/lymphoma) • Burkitt type ALL

  14. Treatment of acute leukemia • Cures are not common except in childhood leukemia. The best hope for a cure in adults lies in bone marrow transplantation. • Three phases: • Induction Therapy: eradicate blast population • Methotrexate and others inhibit DNA synthesis and repair • CNS prophylactic phase: Irradiation • Cytoreductive or Maintenance chemotherapy

  15. Treatment of acute leukemia: con’t • Bone marrow transplantation • Bone marrow is eradicated with chemo and radiation. • Compatible donor cells are transfused and they travel to the empty marrow where they engraft and repopulate the marrow with healthy cells. • Complications include graft vs host (GVH) disease which can be fatal.

  16. References • McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 25." Introduction. Clinical Laboratory Hematology. Boston: Pearson, 2010. Print.

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