1. Chapter 25: Acute Lymphoblastic Leukemia

2. 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.  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. 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 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.  WBC variable from 0.1->50 x 10 9 /L ◦ Usually around 10-12 x 10 9 /L ◦ Neutropenia ◦ Lymphoblasts ◦ Normocytic, normochromic anemia ◦ Thrombocytopenia (48-52 x 10 9 /L)

7. Peripheral Blood Bone marrow Homogeneity of morphology of lymphoblasts

8. Peripheral blood Bone Marrow Heterogeneous morphology of lymphoblasts

9.  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. L1  Small, uniform lymphoblasts  Scant cytoplasm, indistinct nucleoli, occassional clefting of nucleus, chromatin is clumped  Affects primarily children

11. L2  Large, pleomorphic lymphoblasts  Abundant cytoplasm, predominant nucleoli, nuclear clefting and indentation  Affects adults

12. 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.  Two subgroups ◦ Precursor B and T-cell neoplasms(leukemia/lymphoma) ◦ Burkitt type ALL

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