Lecture 4 Acute/Chronic Leukemias

Question 1

What are categories of malignant myeloid leukemias?

Answer 1

There is
1) “Preleukemia” DMPS 1, 2, 3, 4, 5
2) Acute M0, M1, … M7
3) Chronic - PV, CML, AMM, ET

Question 2

What are the categories of Lymphoid leukemias?

Answer 2

Lymphoid leukemias types:
1) Acute (L1, L2, L3)
2) Chronic (CLL, HCL)
3) Plasma cell dyscrasias (MM, PCL, WM, HCD)
4) Lymphomas

Question 3

What are some chronic myeloproliferative disorders?

Answer 3

1. Polycythemia Vera
2. Chronic Myelogneous Leukemia
3. Agnogenic (Idiopathic) Myeloid Metaplasia or Myelofibrosis
4. Essential Thrombocythemia
5. Chronic Neutrophilic Leukemia

Question 4

What is a malignancy?

Answer 4

Malignancy: Deadly or capable of producing death.

Question 5

What is a leukemia?

Answer 5

Leukemia is an acute or chronic disease of unknown etiological factors characterized by unrestrained growth of leukocytes and their precursors in the tissues.

Characterized by abnormal cells in bone marrow and peripheral blood.

Question 6

What are the causes of leukemias?

Answer 6

Leukemias appear to be caused by mutation and altered expression of oncogenes and tumor suppressor genes.

These abnormal oncogenes and tumor suppressor genes produce a cell that either produces an unregulated growth or proliferation or does not respond to control or regulation of the cell cycle.

Question 7

Is Leukemia inherited?

Answer 7

No, but identical twins and family members of a person with leukemia have an increased risk of developing the disease, especially identical twins.

Question 8

What conditions / environment makes developing leukemia more likely?

Answer 8

Developing leukemia is more likely if:
1) Patients with congenital disorders that have an inherited tendency for chromosomal fragility (Bloom’s syndrome, Franconi’s anemia, Down’s syndrome, Klinefelter’s and Turner’s syndrome)
2) Immunodeficiency - hereditary type (i.e. agammaglobulinemia)
3) Chronic Marrow dysfunction - e.g. myelodysplastic syndromes, myeloproliferative disorders –> acute leukemias
4) Ionizing Radiation exposure –> can lead to acute & chronic types
5) Chemical and Drugs (e.g. benzene, or pharmacological agents such as chloramphenicol and phenylbutazone, cytotoxic chemotherapy drugs)
6) Viruses (e.g. T-cell leukemia-lymphoma virus (HTLV-I), HTLV-II isolated from Hairy Cell Leukemia and Epstein-Barr virus.)

Question 9

What is the different in the presentation of anemia, thrombocytopenia, WBC count and organomegaly between acute versus chronic leukemias?

Answer 9

Leukemia differences
1) Acute has mild to severe anemia, whereas chronic is mild anemia only.
2) Acute has mild to severe thrombocytopenia whereas chronic is mild thrombocytopenia only.
3) Acute has a variable WBC count but in chronic WBC is increased.
4) Acute has only mild organomegaly but in chronic case it is prominent.

Question 10

How many blasts are in the marrow / peripheral blood in chronic versus acute leukemia?

Answer 10

Chronic leukemia < 30% blasts in marrow (rule, FAB? Classification); <= 5% in peripheral blood (guideline)
Acute leukemia > 30% blasts in marrow (often almost 100%) (rule, FAB?); > 5% blasts in peripheral blood (guideline)

Question 11

What are chronic myeloproliferative disorders?

Answer 11

Chronic myeloproliferative disorders:
1) Result of malignant transformation of pluripotent stem cell defect showing proliferation of one or more cell lines.
2) Abnormal proliferation of granulocytes, erythrocytes, megakaryocytes, and fibroblasts involved.
3) Shares common clinical and hematological features with own individual characteristics.

Question 12

In what way does Chronic Myelogenous Leukemia mimic a leukemoid reaction due to inflammation?

Answer 12

CML mimics a leukemoid reaction by:
1. High WBC count
2. Left Shift
3. Elevated platelet count.

Question 13

How can the doctor distinguish CML from a leukemoid reaction?

Answer 13

Test for LAP. CML shows decreased LAP whereas infections and inflammations show increased activity.
CML would also be without a fever.

Question 14

What does the bone marrow look like in CML?

Answer 14

CML bone marrow is:
1. Hypercellular with decreased fat spaces due to myeloid hyperplasia.
2. Most cells display various stages of granulocytes.
3. Megakaryocytes frequently increased.
4. Reticulin stain may demonstrate increased fibrosis.

Question 15

What chemical tests are increased in CML?

Answer 15

Uric acid, LDH and serum B12 are all increased in CML due to increased destruction of leukocytes.

Question 16

What are the characteristics of the peripheral blood in CML?

Answer 16

CML peripheral blood findings:
1. Left shift of granulocytes. Basophilia and/or eosinophilia.
2. Thromboctyosis.
3. Marked leukocytosis, 50-600x10^9/L before treatment.
4. Anemia usually normocytic, normochromic.
5. Platelet counts variable.
6. Megakaryocytes crowded out due to increased granulocytes in marrow.
7. All stages of granulocyte development.

Question 17

What is myelofibrosis (AMM)?

Answer 17

Myelofibrosis (AMM) is characterized by proliferation of fibroblasts, deposition of reticulin & collagen fibres and over production of granulocytes, and abnormal megakaryocytes in bone marrow and extra medullary sites (i.e. spleen, liver).

Question 18

Why is platelet derived growth factor (PDGF) released in Myelofibrosis (AMM)?

Answer 18

In Myelofibrosis (AMM) defective platelets from abnormal megakaryocytes result in premature death of platelets releasing Platelet Derived Growth Factor (PDGF).

Question 19

What is the impact of releasing of Platelet Derived Growth Factor (PDGF) in Myelofibrosis (AMM)?

Answer 19

PDGF released results in alpha granules stimulating fibroblastic growth, secretion of collagen and laying down of reticulin fibers.

Resulting in a marrow with increased in fibrous tissue and myelofibrosis.

Question 20

What are the main finding in the peripheral blood in Myelofibrosis?

Answer 20

Myelofibrosis Peripheral Blood Findings:
1. WBC’s and Platelet counts variable.
2. RBCs usually normocytic, normochromic.
3. Tear drop shape cells typical (due to spleen)
4. May have increased eosinophils and basophils.
5. Immature granulocytes & RBCs (Leukoerythroblastic) with one or more of these: NRBCs, giant abnormal platelet, rare megakaryocytic fragment, occ’l immature myeloid cell, and rare blast cell.

Question 21

What is the peripheral blood findings of Essential Thrombocythemia (ET)?

Answer 21

Essential Thrombocythemia (ET) Blood Findings:
1. Very high platelet count. 600 to 2500 up to 14,000.
2. Large masses of platelet aggregates w/ many abnormal giant & bizarre forms.
3. Platelet anisocytosis and occ’l megakaryocytic fragments.
4. RBCs: Howell-Jolly bodies, target cells, and acanthocytes may be present if splenic infarction.

Question 22

How does one differentiate between Essential Thrombocythemia (ET) and Reactive Thrombocytosis?

Answer 22

Differentiate ET by:
1. Platelet function test. Normal in reactive thrombocytosis.
2. Spleen and liver normal in reactive thrombocytosis.
3. Bleeding and thrombosis unlikely in reactive conditions.
4. Platelet count in ET frequently above 1500, reactive thrombocytosis rarely above 1000.

Question 23

What are the symptoms of Essential Thrombocythemia (ET)?

Answer 23

Symptoms of ET are:
1. Freq. Nosebleeds (epistaxis), vomiting of blood, easy bleeding after dental surgery & gastrointestinal bleeding.
2. Thrombotic events are common.
3. Fatigue, neurological disturbances (headaches, visual disturbances, dizziness, rare seizures).

Question 24

What are physical findings in Essential Thrombocythemia (ET)?

Answer 24

ET Physical Findings:
1. Splenomegaly & occ’l hepatomegaly.
2. Splenic atrophy (from platelet aggregates).
3. Pulmonary emboli and gangrenous extremities.
4. Recurrent abortions and fetal growth retardation reported.

Question 25

What are the clinical findings for chromic neutrophilic leukemia (CNL)?

Answer 25

Clinical findings of CNL:
1. Hepatosplenomegaly w/ nausea, abdominal pain, inability to eat normal amounts of food.
2. Afebrile (not feverish)
3. May have hemorrhagic episodes.
4. Mild anemia.

Question 26

What are the findings in the peripheral blood in Chronic Neutrophilic Leukemia (CNL)?

Answer 26

Peripheral Blood Findings in Chronic Neutrophilic Leukemia (CNL):
1. Persistent neutrophilic leukocytosis w/o left shift.
2. WBCs as high as 100.
3. Platelets normal to slightly decreased.
4. Absence of eosinophilia and basophilia.
5. LAP scores extremely high.

Question 27

What is the % of mature granulocytes in the marrow in the case of Chronic Neutrophilic Leukemia (CNL)?

Answer 27

CNL Bone Marrow.
1. Mature granulocytes make up 90% of bone marrow.
2. Marked cellularity with neutrophilic hyperplasia.