Myeloid and Lymphoid Leukemia

Cause of Death in Leukemia

-Anorexia & weight loss - decreased immunity -Anemia leads to tissue hypoxia & damage -Organ infiltration - reduced liver, kidney, spleen, LN function -Frequent infection from poor neutrophil function -Abnormal bleeding or hemolysis

CBC Findings in Leukemia

-Large buffy coat (high cell counts - WBC, platelets) -Presence of blast cells (immature chromatin with often prominent nucleoli) -Abnormal cell morphology with developmental changes (dysplasia) e.g., "asynchronous maturation" -Altered WBC: leukocytosis, leukopenia -Anemia: most often nonregenerative -Thrombocytopenia is common

clinical signs in leukemia

-Lethargy -Anorexia and weight loss -Pale mucous membranes -Icterus -Fever and frequent infection -Abnormal bleeding or hemolysis -Organ system failure or enlargement - Liver - Spleen or Lymph Nodes or Tonsils

causes of leukemia

-Virus infections such as FeLV or BLV (Feline or Bovine Leukemia Virus) -Genetic abnormalities -Defective immune systems induced by FIV (Feline Immunodeficiency Virus) -Rare conditions include exposure to: - Chemicals - Radiation

Myeloproliferative Neoplasms (Chronic) diagnosis

20% myeloid blasts in bone marrow with increased cell counts of the affected line

Acute vs Chronic Myeloid Leukemia (Nonlymphoid)

Acute leukemia - Increased number of blast cells - Blast cells greater >/= 20% of nucleated BM cells Myeloproliferative neoplasia (Chronic) - Predominance of mature cells - Blast cells < 20% of BM cells

Acute Myeloid Leukemia Common Classification Subtypes

Acute myeloblastic leukemia -Granulocytes, with or w/o maturation Acute myelomonocytic leukemia -Neutrophils and monocytes Acute monocytic leukemia -Monocytes, with or w/o maturation Erythroleukemia -Neutrophils and erythroid or erythroid mostly Acute megakaryoblastic leukemia -Megakaryocytes

Other Routine Diagnostic Tests for Leukemia

Biochemical profile to detect organ failure Imaging for organ involvement Bone marrow aspirate/core biopsies Cytology of effusions or solid tissue masses Serology for leukemia viruses Serum or urine protein evaluation

Myeloproliferative Neoplasms (Chronic) Classification Subtypes

Chronic myelogenous/neutrophilic leukemia (neuts) Eosinophilic leukemia Basophilic leukemia Chronic myelomonocytic leukemia (neuts/monos) Polycythemia vera (erythroid mostly) Essential (or primary) thrombocythemia (platelets) Primary myelofibrosis (neuts & megas /reactive fibrosis)

Advanced Diagnostic Tests for Leukemia

Cytochemistry (cytoplasmic substances) Flow cytometry (quantitative for various cellular features) Immunochemistry (immunologic features) -immunocytochemistry (cells) -immunohistochemistry (tissues) Electron microscopy (morphologic features) Genetic studies

Prognosis of Lymphoproliferative disorders vs. myeloproliferative disorders.

Lymphoproliferative disorders generally have a better prognosis than myeloproliferative disorders. One cell line versus multiple cell lines

Myelophthisis

the crowding out in the bone marrow of normal hematopoietic elements by increased numbers of abnormal cells or stroma. Such conditions include leukemia, myelofibrosis, and excessive bone production.

Multiple Myeloma

Malignant proliferation of a plasma cell population -usually, IgG or IgA is produced in large amounts Definitive diagnosis requires 2 of these 4: -radiographic bone lesions (vertebrae, long bones, ribs, pelvis) -bone marrow infiltration with plasma cells (>20%) -monoclonal gammopathy -Bence Jones proteinuria or paraproteinuria NOTE that hyperproteinemia may not be observed! Treatable; prognosis often worse for cats than dogs

Who survives longer: chronic or acute leukemia?

Patients with chronic leukemias survive longer than those with acute leukemias. Years versus months

Lymphoid Cell Disorders

Preneoplastic Condition -Persistent Lymphocytosis Neoplastic Conditions -Lymphoid leukemia (Acute or Chronic) -Granular lymphocyte leukemia/lymphoma -Plasma cell tumors (BM or Extramedullary) -Lymphoma (Nodal, Extranodal)

Acute Lymphoblastic Leukemia

Rapidly progressive disorder Age ranges from young to old (mean = 6 yrs) Organomegaly common with lymph node minimally involved WBC counts variable with increased blast cells (Note: No blast % cutoff for BM is necessary) Anemia, thrombocytopenia, occ. gammopathy B-, T-, or null-cell types Untreated cases survive less than 3 months

Chronic Lymphocytic Leukemia

Slow and protracted course of months to years Middle age to older dogs (median = 10 yrs) Splenomegaly or hepatomegaly may be present Mostly T-cell or granular cell types predominate Marked lymphocytosis, often > 100,000/ul but may range from 15,000 to 1.6 million Mild anemia and variable thrombocytopenia Therapy given when clinically necessary

Maturation

the morphologic development of a specific cell type to full function.

Differentiation

indicates commitment to a specific cell lineage, such as myeloid or lymphoid.

Leukemoid Reaction - Hyperplastic

WBC > 50,000/l Marked granulocyte immaturity Left shift back to metamyelocytes and myelocytes; occ. progranulocytes. No Blasts Toxicity likely present Caused by severe inflammation; site often readily apparent e.g., pyometra, pneumonia

Myeloproliferative Neoplasms (Chronic) prognosis

months to years

Myeloproliferative Neoplasms (Chronic) treatment

supportive care, antineoplastic agents

Megaloblast

a dysplastic nucleated erythroid precursor having abundant mature cytoplasm and an eccentrically placed immature nucleus.

Myelodysplastic syndrome

a group of clonal hematopoietic stem cell diseases characterized by significant dysplasia of one or more of the myeloid cell lines, frequent bone marrow hyperplasia, and peripheral cytopenias. Myeloblasts account for less than 20% of the nucleated bone marrow cell population. These diseases have an increased risk of development of acute myeloid leukemia.

Acute myeloid leukemia

a group of neoplastic diseases characterized by increased numbers of myeloblasts in the bone marrow. The suggested cutoff is greater than or equal to 20% blast cells of the nucleated bone marrow cell population. Peripheral cell counts are variable

Myeloproliferative neoplasms

a group of neoplastic disorders characterized by less than 20% blast cells in the bone marrow that is generally classified by the predominant recognizable cell type (also known as chronic myeloid leukemia). Compared with myelodysplastic syndromes that have ineffective hematopoiesis, these disorders often have effective hematopoiesis with markedly increased peripheral cell counts (cytosis).

Dyserythropoiesis

a maturation abnormality of erythroid cells resulting in macrocytes (large cells with no nucleus without polychromasia), megaloblasts (large immature cells with a nucleus), sideroblasts (iron-containing particles within erythroid precursors, and fragmented nuclear chromatin, asynchrony in maturation of nucleus and cytoplasm

Dysgranulopoiesis

a maturation abnormality of granulocytes resulting in macropolycytes (cell giantism), nuclear hypersegmentation, hyposegmentation, abnormal cytoplasmic granulation, and multinucleation.

Dysthrombopoiesis

a maturation abnormality of platelets and megakaryocytes resulting in asynchronous maturation (dwarf megakaryocytes/micromegakaryocyte), hypogranulation or vacuolated platelets, hypergranulation, and platelet giantism.

Leukemia

a neoplastic disease of blood and/or bone marrow which may be primary and arise from the bone marrow or represent a secondary metastatic disease.

Multiple myeloma

a neoplastic disease of plasma cells in the bone marrow that requires 2 of the 4 features for diagnosis. These features include bone marrow plasmacytosis, monoclonal gammopathy, Bence-Jones urine protein, and bone lysis.

Neoplasia

a non-purposeful, unregulated new growth.

Lymphoma

a solid tissue proliferation of neoplastic lymphoid cells.

Dysplasia

abnormal cell development with altered nuclear and cytoplasmic morphology and relative proportions. Concerning hematopoiesis, a general term of dysmyelopoiesis is used to include dyserythropoiesis, dysgranulopoiesis, and dysthrombopoiesis.

Asynchronous maturation

an abnormality of cell development in which the nucleus and cytoplasm mature at a different rate such that a cell may have an immature nucleus with a mature cytoplasm.

Dysmyelopoiesis

an abnormality of cell development that may exist by itself or proceed into neoplasia.

Leukemoid reaction

an exuberant hyperplastic response to inflammation in which the leukocyte count is greater than 50,000 with a left shift that extends back to myelocytes with rare progranulocytes.

Chronic leukemia

characterized by a predominance of mature cells with recognizable lineage in either the myeloid or lymphoid cell lines.

Acute leukemia

characterized by increased numbers of blast cells of myeloid or lymphoid origin present in the bone marrow, which may have prominent nucleoli but always have immature nuclear chromatin.

Myeloid

the nonlymphoid cells which arise from the pluripotential stem cell that produces precursors for granulocytes, monocytes, erythrocytes, platelets, and some dendritic cells