MLAB 1415: Hematology Keri Brophy-Martinez 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. Arise from the HSC, the common lymphoid progenitor cell OR differentiated progenitors of the T or B cell lineage 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

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.

Incidence Seen in young children Another peak seen in 60’s 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 peak seen in 60’s Onset symptoms rapid, fatigue, infections, bruising Prognosis not good

Clinical Findings 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

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

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

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

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 B, negative TdT ALL - negative peroxidase and Sudan black B, positive TdT

WHO Classification Two subgroups B-cell neoplasms T-cell neoplasms Precursor B cell Mature B cell neoplasms T-cell neoplasms Precursor T cell Mature T cell neoplasms

Treatment of acute leukemia Three phases: Induction Therapy: eradicate blast population CNS prophylactic phase: Irradiation Cytoreductive or Maintenance chemotherapy

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