Chronic Myeloid Leukemia

Myeloproliferative Neoplasm

An acquired hematopoietic neoplasm that has unregulated differentiation and proliferation of hematopoietic stem cells. There is trilineage involvement and mutations are seen in both the bone marrow and peripheral blood.

7 MPNs - WHO Classification

Chronic Myeloid Leukemia

Primary Myelofibrosis

Polycythemia Vera

Essential Thrombocythemia

Chronic Neutrophilic Leukemia

Chronic Eosinophilic Leukemia

Myeloproliferative Neoplasm - Unclassifiable

4 MPNs - Major Classifications

Chronic Myeloid Leukemia

Primary Myelofibrosis

Polycythemia Vera

Essential Thrombocythemia

Chronic Myeloid Leukemia - Other Names (2)

Chronic Myelogenous Leukemia

Chronic Granulocytic Leukemia

Primary Myelofibrosis - Other Names (3)

Chronic Idiopathic Myelofibrosis

Myelofibrosis with Myeloid Metaplasia

Agnogenic Myeloid Metaplasia

MPNs - Clinical Findings

Weakness

Infection

Thrombosis

Hemorrhage

Pallor

MPNs - Hematologic Findings

Basophilia

Anemia (or Polycythemia)

Leukocytosis

LE Picture

Thrombocytosis (bizarre platelets)

MPNs - Bone Marrow Findings

Hypercellular → Fibrotic (increased reticulin fibers) → Extramedullary hematopoiesis

Chronic Myeloid Leukemia

A type of MPN characterized by uncontrolled proliferation of granulocytic cells.

CML - Incidence

20% of all US leukemia cases

CML - Age of Onset

40-59

CML - 3 Phases

1) Chronic Phase

2) Intermediate Transitional/Aggressive Phase

3) Blast Crisis/Acute Leukemia Phase

CML - Chronic Phase

Characterized by splenomegaly and leukocytosis

Abdominal discomfort due to splenomegaly

Left shift with myelocyte bulge

Basophilia

Arthritis caused by gout

How long does the chronic phase of CML typically last?

2-3 years

CML - Intermediate Transitional/Aggressive/Accelerated Phase

10-19% myeloblasts in peripheral blood or bone marrow

>20% basophils in the peripheral blood

Bone pain

Chromosome abnormalities

How long does the intermediate transitional/aggressive phase of CML typically last?

1-1.5 years (medication response is typically poor)

CML - Blast Crisis/Acute Leukemia Phase

Peripheral blood and bone marrow contain >30% blasts (with skin or tissue infiltration)

Blasts are commonly myeloid (lymphoid in 1/3 of cases)

Extreme basophilia and thrombocytosis

Further chromosome abnormalities

How long does the blast crisis/acute leukemia phase of CML typically last?

3-6 months (very difficult to treat)

CML - Hematologic Findings

Leukocytosis with left shift

Increase in all granulocyte precursors (<10% promyelocytes and blasts)

Absolute eosinophilia and/or basophilia

N/N mild-moderate anemia

Variable platelet counts

CML - Bone Marrow Findings

90-100% hypercellular

M:E ratio 10:1 to 100:1

<20% blasts, Auer rods unusual

Prominent megakaryocytes

Mild fibrosis

What is the chromosomal abnromality associated with CML?

Philadelphia Chromosome

Philadelphia Chromosome - Mutation

Reciprocal translocation between chromosomes 9 and 22

t(9; 22)(q34; q11)

abl on chromosome 9 is relocated to chromosome 22 (bcr region)

Philadelphia chromosome = resulting abnormally short chromosome 22

Philadelphia Chromosome - Diagnostic Significance

Must be present (or evidence of bcr/abl fused gene) in order to diagnose CML

Philadelphia Chromosome - Prognostic Significance

Patients that lack the Philadelphia chromosome often have:

• Thrombocytopenia

• Absence of basophilia

• Poor response to therapy

• Short survival

LAP Stain in CML

Helps distinguish CML from leukemoid reaction or infection

CML will have LAP score <40

Leukemoid reaction will have LAP score >100

CML - Treatment Options

Gleevec (tyrosine kinase inhibitor)

Allogeneic bone transplantation (patients <55)

Interferon as alternative

Leukocyte apheresis when counts >300 × 10⁹/L

CML - Prognostic Risk Factors

Basophilia

Decreased megakaryocytes

Splenomegaly

Myelofibrosis

Patient age

Anemia

Negative Philadelphia chromosome (after therapy)

Thrombocytopenia/Thrombocytosis

Symptoms at presentation

Chronic Neutrophilic Leukemia - Characteristics

Leukocytosis without immature granulocytes

Elevated neutrophil count

Hypercellular bone marrow (granulocytic hyperplasia)

Philadelphia chromosome negative

LAP increased

Rule out other causes of neutrophilia and CML

Chronic Eosinophilic Leukemia

Eosinophils increased in blood, bone marrow, and tissues (>1500 uL)

Organ and tissue damage caused by eosinophils

Philadelphia chromosome negative

LAP normal

Poor prognosis

What is the alternative name for chronic eosinophilic leukemia?

Hypereosinophilic Syndrome (HES)