Acute Leukemias

• a mutation of stem cells in the bone marrow

• causes impaired production of normal RBCs, WBCs, and platelets

In general, what is leukemia?

• leukemias of the myeloid line

  • granulocytes, monocytes, megakaryocytes, and erythrocytes

• leukemias of the lymphoid line

  • lymphocytes only

What are the 2 lines of leukemia?

• acute leukemia

  • PBS consists of mostly immature cells (blasts)

  • quick onset

  • may occur at any age

• chronic leukemia

  • PBS consists of mature cells (just higher in number)

  • slow onset

  • usually seen in adults

Cell maturity is used to determine the type of leukemia. What are the 2 types?

• chromosome abnormalities

  • causes uncontrolled cell proliferation

• genetics

• toxic exposure

What 3 things can cause acute myeloid leukemia (AML)?

• clinical features

  • dysfunctional cells can lead to anemia and infection (fatigue and weakness)

  • thrombocytopenia causes easy bruising and mucosal bleeding

• lab findings

  • CBC

    • blood cell counts can vary

    • pancytopenia possible

    • thrombocytopenia

  • PBS

    • blasts, auer rods, nRBCs, pseudo and hypersegmentation 

What are the clinical features and lab findings in AML?

• diagnosis

  • 200 WBCs must be counted in the PBS

  • the blast % is calculated by a 500 cell diff in the bone marrow

  • cytochemical stains

    • done on peripheral or bone marrow smears

    • specific dyes are used to identify specific lineages of blast cells

  • chromosome analysis, genetic studies, flow cytometry, and electron microscopy

• prognosis

  • older patients have a worse prognosis

  • disease related factors can predict resistance to chemo

    • splenomegaly, extramedullary disease, or a secondary leukemia

How is AML diagnosed and what is the prognosis?

• myeloblasts have auer rods, lymphoblasts do not

• myeloblasts have a moderate amount of cytoplasm and looks basophilic, lymphoblasts do not have a lot of cytoplasm

• cytochemical stains can also determine the cell lineage

When looking at a slide of a patient with AML, how can you tell you’re looking at myeloblasts and not lymphoblasts?

• a malignancy caused by mutations in lymphoid precursor cells in the bone marrow

• predominant in kids, adolescents, and young adults

• unknown causes

  • may be environmental factors such as ionizing radiation

  • or genetics

What is acute lymphoblastic leukemia (ALL)?

• clinical features

  • fever, pallor, fatigue, bleeding, bone and joint pain, hepatosplenomegaly

• lab findings

  • variable WBC

  • anemia and thrombocytopenia

  • blood and bone marrow show lymphoblasts twice the size of normal small lymphocytes (may or may not have vacuoles)

  • picture shows B lymphoblastic leukemia (B-ALL)

What are the clinical features and lab findings in ALL?

• T-ALL prognosis is poorer in children, B-ALL prognosis is better

  • opposite for adults: T-ALL is better than B-ALL, overall survival rate is 60%-70%

• children with favorable prognoses can be treated with less toxic regimines

• treatment: chemotherapy, immunotherapies, molecular testing

• picture shows B-ALL

What is the prognosis and treatment of ALL?

the replacement of normal marrow precursors by leukemic cells

What is responsible for producing signs and symptoms in leukemia?

• B-ALL/lymphoma, not otherwise specified

• B-ALL/lymphoma with recurrent genetic abnormalities

• T-ALL/lymphoma

• about 75% of all adult ALL cases are B-ALL

In 2008, the WHO classified 3 major categories of ALL, what are they?

• AML with recurrent genetic abnormalities

• AML with myelodysplasia-related changes

• therapy-related neoplasms

• AML not otherwise specified

What are the 4 categories of AML classified by the WHO?

• uses monoclonal antibodies that are directed against CD markers on blasts to identify the type of blast present

• can detect the lineage and stage of maturation of the blast cells

  • distinguishes between AML and ALL, and B-ALL and T-ALL

How is immunophenotyping used to diagnose acute leukemias?