1. MLAB 1415: Hematology Keri Brophy-Martinez
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.
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

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. 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

5. 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

6. Lab Features WBC variable from 0.1->50 x 109/L Neutropenia
Usually around 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 B, negative TdT
ALL - negative peroxidase and Sudan black B, positive TdT

10. 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

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

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