LEUKEMIA

What is Leukemia?

cancer of the stem cells of the hematopoietic system, most commonly the white blood cells, aka cancer of the bone marrow and blood

Leukemias are broadly divided into classifications based on onset and progression:

• Acute: onset of symptoms and disease spread is rapid

• Chronic: onset of symptoms and disease spread is slow

They are further categorized by cell origin:

• Lymphocytic (white blood cells, T cells, B cells etc.)

• Myeloid (myelogenous) - includes neutrophils, basophils etc.

What are the four main types of Leukemia?

◦ Acute Lymphoblastic Leukemia (ALL)

◦ Acute Myeloid Leukemia (AML)

◦ Chronic Myeloid Leukemia (CML)

◦ *Chronic Lymphocytic Leukemia (CLL)- now recognized to be the same cancer as small lymphocytic lymphoma (SLL), a type of non-Hodgkin Lymphoma

Which leukemia cancer type is classified the same cancer as small lymphocytic lymphoma (SLL), a type of non-Hodgkin Lymphoma?

Chronic Lymphocytic Leukemia (CLL)

What is the most common types in Adults (20 years or older)?

CLL (38%)

• ALL (31%)

Most common types among children and adolescents (ages 0-19years)?

ALL (76%)

• AML (16%)

What is the etiologic factors of Leukemia?

◦ Exposed to high-levels of ionizing radiation (usually form previous cancer tx)

◦ Certain types of chemotherapy exposure

◦ Certain genetic abnormalities or inherited syndromes (i.e. Li-Fraumeni or Down syndrome)

◦ Workers exposed to certain chemicals, such as benzene (e.g., during oil refining or rubber manufacturing)

◦ Cigarette smoking increases the risk of AML in adults (evidence that parental smoking before and after childbirth increases risk of childhood leukemias

What are the general acute clinical presentations?

◦ Symptoms appear suddenly

◦ Spread more rapidly

◦ Fatigue

◦ Weight loss

◦ Repeated infections

◦ Bleeding and bruising easily

◦ Bone or joint pain

◦ Swelling

What are the general chronic clinical presentations?

◦ Manifest over a longer period of time

◦ Individuals can live with disease for years before diagnosis

◦ Cancer cells begin to change at a slower rate

◦ Often times diagnosed because of abnormal blood cell counts

__ % of all leukemias are acute?

50

ALL has peak incidence at what age (rare over age of 50)?

2-3 years old

How does ALL develop & where does it originate?

Develops from overgrowth of lymphocytes (a type of white blood cells) which limits the growth of healthy cells

◦ Originates in bone marrow

TRUE OR FALSE? ALL can spread quickly to circulating blood.

True

Where does ALL most commonly metastasize to?

most commonly to lymph nodes, liver, spleen, and CNS

Symptoms of ALL:

ethargy, dizziness, fever, bruising easily, consistent infections that are hard to clear, bleeding, night sweats, unexpected weight loss or anorexia, pain in bones or joints, swollen lymph nodes in neck, armpits, or groin, swelling or discomfort in abdomen, and shortness of breath

Etiologic factors of ALL?

◦ Can be caused by previous exposure to ionizing radiation from previous tx

◦ Correlated risk from atomic bomb explosion or nuclear accidents exposure

◦ Exposure to benzene (a product used in cigarettes, some cleaning supplies, and detergents) increases risk

◦ Infection of the human T-cell lymphoma/leukemia virus-1 (HTVL-1) is known to cause a rare form of T-cell leukemia (rare in U.S., more prominent in Japan and Caribbean)

What does ALL present with?

large number of lymphoblasts in blood

What is important in detection and diagnosis of ALL?

◦ Bone marrow aspiration important to diagnosis of all blood disorders

◦ Lumbar puncture important because spread can occur throughout

What is the initial test of ALL?

blood panel

What is the mainstay tx of ALL?

Chemo

What are common chemo drugs for ALL?

Vincristine and Daunorubicin

When is targeted therapy used in tx of ALL?

patients who have specific genetic chromosome changes which initiated the disease:

◦ *Philadelphia Chromosome (genetic info from chromosome 9 and 22 has been swapped)

Radiation Therapy is not mainstay tx of ALL but when is it used?

◦ palliate symptoms of bone pain if spread has occurred to bone

◦ treat brain or spine if spread to CNS has occurred

◦ irradiate whole body as part of process to prep for bone marrow or peripheral blood stem cell transplant

What is Acute Myeloid Leukemia (AML)?

overgrowth of cells that are unable to differentiate in response to hormonal signals and cellular interactions

◦ Cells either do not mature or mature with defects

Where does AML originate?

Like ALL, starts in bone marrow and can quickly move into bloodstream

TRUE OR FALSE? AML is relatively common.

False

Etiologic factors of AML:

Smoking, exposure to ionizing radiation, exposure to benzene, previous use of alkylating chemo drugs, and older age are risk factors

Average age of diagnosis of AML?

usually older than 40, with an average age at diagnosis of 67-68

AML prognosis not as good as ALL, WHY?

older typical diagnosis age, complex genetic mutations, and higher rates of treatment resistance and relapse

What is present in diagnosis of AML?

Auer rods are present in leukemic cells

What are Auer rods?

pink or red stained needle-shaped structures seen in the cytoplasm of myeloid cells

How is AML typically treated?

chemo

Common chemo drugs for AML?

Cytarabine and Daunorubicin

When are targeted drugs used for AML?

specific patients with specific genetic mutations

such as FLT-3

When is radiation therapy used for AML?

used before bone marrow transplantation and palliation

What is CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)?

Derived from cells that would become white blood cells or lymphocytes, but unlike ALL, the cells may still exhibit some characteristics of the lymphocytes and so are allowed to grow and manifest slowly over time

TRUE OR FALSE? Many people with CLL are unaware of their disease for years, allowing the opportunity for the disease to spread to lymph nodes, liver and spleen); organs become enlarged and bone marrow function lessened

True

Average age of diagnosis of CLL?

Average age is 65-70

• Rarely occurs in persons under 40 and virtually nonexistent in children

What are major risk factors of CLL?

age, exposure to Agent Orange (powerful herbicide

used by military during Vietnam War to eliminate herbs and crops), and having a family history of CLL

Which leukemia cancer is exposure to radiation not a risk factor?

CLL

How is CLL diagnosed?

blood samples, bone marrow aspirations, and flow cytometry

What is the tx of choice for CLL?

chemo (purine analogs, alkylating agents, and

corticosteroids)

In addition to chemo, which cancer includes monoclonal antibodies (synthetic antibodies which target specific proteins on surface of cancer cells- like Rituximab) to their tx regimen?

CLL

TRUE OR FALSE? In tx of CLL, EBRT is not used unless for palliative purposes of prep for stem cell transplant

True

What is CHRONIC MYELOGENOUS LEUKEMIA (CML)?

Identified as a genetic change to myeloid stem cells

Along with ALL, which cancer mainly has abnormal hematopoietic stem cells that contain the Philadelphia chromosome?

CML

What is increased in CML patients and what is damaged?

Increase in granulocytes and megakaryocytes

◦ Erythrocytes become damaged

What is the average age of diagnosis of CML?

Rare in children, common age in mid-60s

What are the only risk factors of CML?

previous radiation exposure, increased age, and slight

increase in males over females

What are the 3 stages of CML?

• chronic

• accelerated

• blast crisis

TRUE OR FALSE? CML is typically found when testing for other illnesses, most don’t experience symptoms

True

For CML, what is necessary after identifying elevated WBC?

Blood testing and bone marrow aspirations

Why is genetic testing done for CML?

Genetic testing must be done to identify Philadelphia chromosome or BCR-ABL gene

What is the main course of tx of CML?

BCR-ABL is a protein known as tyrosine kinase, therefore targeted therapies, including tyrosine inhibitors are main course of treatment

True or false? Radiation therapy does not play large role in treatment of CML except to treat bone pain or if pain occurs due to spleen enlargement, or preparing for stem cell transplant.

True

What is a newer treatment that boosts the body’s immune system and has shown promise against hard to treat leukemias?

Chimeric Antigen Receptor (CAR) T- Cell Therapy

5 year survival for all Leukemias?

68%

Among youth (ages 0 to 19 years) survival rate?

◦ 71% for AML

◦ 90% for ALL

◦ 91% for CML

Among adults (20 years and older) survival rates

◦ 30% for AML

◦ 49% for ALL

◦ 70% for CML

◦ 89% for CLL