Module 10.1 - Leukemias

Question 1

What is leukemia?

Answer 1

• A malignant disorder of leukocytes primarily in the bone marrow, and usually, but not always of the blood.
• Common feature of all forms of leukemia is an uncontrolled proliferation of malignant leukocytes, causing an overcrowding of normal bone marrow and decreased production and function of normal hemopoietic cells (red blood cells, white blood cells and platelets).
• In the majority of cases, leukemic cells may infiltrate the blood, where they will accumulate in the liver, spleen, lymph nodes and other organs throughout the body.

Question 2

What are the differences between acute vs chronic leukemia?

Answer 2

Acute leukemia:

• Characterized by undifferentiated or immature cells, usually a blast cell
• Onset of disease is abrupt and rapid
• Short survival time

Chronic leukemia:

• Predominant cell is more differentiated, but functions abnormally
• Relatively slow progression

Question 3

What are some characteristics of Chronic Lymphocytic Leukemia (CLL)?

Answer 3

• Etiology is unknown; familial tendency suggest genetic linkage
• Genetic anomalies occur in approx. 90% of cases, frequency as deletions
• In adults, CLL is the most common leukemia in the western world.
• Slow-growing cancer, insidious in onset
• Median survival, approx. 6 years
• Most individuals are asymptomatic at time of diagnosis
• Too many immature lymphocytes found mostly in blood and bone marrow.
• Cells are well differentiated and easily identifiable
• Longer life expectancy
• Peak incidence in 5th to 6th decade of life; rare in persons < 45 years of age
• CLL is identical to small lymphocytic lymphoma

Question 4

Describe the pathophysiology associated with Chronic Lymphocytic Leukemia (CLL)?

Answer 4

• Involves malignant transformation and progressive accumulation of monoclonal B lymphocytes
• Rarely (<5%) are CLL malignancies of T cell origin
• Derived from a transformation of a partially mature B cell that has not yet encountered antigen.
• Most significant effect of CLL is suppression of humoral immunity and increased infection with encapsulated bacteria
• Invasion of most organs is uncommon, but infiltration does occur in lymph nodes, liver, spleen and salivary glands.
• CNS involvement is rare

Question 5

What are the subjective/physical exam findings associated with Chronic Lymphocytic Leukemia (CLL)?

Answer 5

• Lymphadenopathy- when symptoms do appear- most common finding, 80% of cases
• In about 10% of cases, development of a more severe aggressive malignancy occurs, which is usually a diffuse large B-cell lymphoma. When this occurs, symptoms such as: extreme fatigue, weight loss, night sweats, low-grade fever, elevated levels of lactic dehydrogenase, hypercalcemia, anemia and thrombocytopenia are common

Question 6

What are the laboratory findings associated with Chronic Lymphocytic Leukemia (CLL)?

Answer 6

• Lymphocytosis- hallmark finding of disease:
  
  • Minimum level > 5000/microL
  • Usual range is 40,000-150,000 /microL
• Lymphocytes constitute 75-98% of circulating cells
• Smudge cells (prognostic indicator of CLL, remnants of cells that lack any identifiable cytoplasmic membrane or nuclear structure) seen on peripheral smear
• HYPOgammaglobulinemia present in 50% of cases
• Immunoglobulin IgG, IgA and/or IgM low at diagnosis and decreasing as disease

Question 7

How do you manage a patient with Chronic Lymphocytic Leukemia (CLL)?

Answer 7

• Hematology/oncology referral
• History, PE, peripheral blood count and lymphocyte morphology are usually all that are required to diagnose CLL in clinical setting.
• No specific therapy, ‘watchful waiting’, for patients in early stage of disease.
• Treatment begun when symptoms appear
• Monitor for LAD, anemia and thrombocytopenia; treat whether symptomatic or not if present
• Treatment based on RAI system- prognostic staging system
• Chemotherapy based on RAI stage, age, and presence or absence of deletions at 11q and 17p.
• Chemotherapy often combined with targeted therapy drug (monoclonal antibody) and/or an immunotherapy agent.
• Splenectomy in selected cases
• Radiation limited to localized nodal masses that are refractory to chemotherapy
• Supportive care:
  
  • Annual influenza vaccine
  • Pneumococcal vaccine q 5 years- Prevnar preferred
  • Avoid all LIVE vaccines include Zoster

Question 8

What are some characteristics of Chronic Myelogenous Leukemia (CML)?

Answer 8

• Several forms of CML can occur (depended upon lineage of malignant cells):
  
  • Chronic neutrophilic leukemia (CNL)
  • Chronic eosinophilic leukemia (CEL)
• Mostly a disease of adults (median ager 67), but can occur in children and adolescents
• Member of the family of myeloproliferative disorders
• Accounts for 7-15% of adult leukemia
• Only known cause is ionizing radiation – atom bomb survivors have a dose related increased incidence of CML that peaks 5-12 years after exposure; otherwise cause unknown, but suspect chromosomal abnormality
• Median survival 3-4 years, but targeted agents are increasing survivability

Question 9

What are the 3 phases of Chronic Myelogenous Leukemia (CML)?

Answer 9

• Chronic phase: lasts 2 to 5 years where symptoms may or may not be present
• Accelerated phase: 6 to 18 months- primary symptoms usually develop; characterized by excessive proliferation and accumulation of malignant cells.
• Terminal Blast Phase: blast crisis with survival of only 3 to 6 months; characterized by rapid and progressive leukocytosis with an increase in the number of basophils; later phase resembles AML, blast cells or pro-myelocytes predominate and the individual experiences a blast crisis.

Question 10

What are the subjective/physical exam findings associated with Chronic Myelogenous leukemia (CML)?

Answer 10

• Splenomegaly- most common finding- may be prominent and painful
• Lymphadenopathy is NOT usually present.
• Hepatomegaly occurs, but liver function rarely altered.
• Hyperuricemia common- produces gouty arthritis
• Infections, during blast crisis
• Fever,
• Weight loss
• Fatigue
• Diminished exercise tolerance,

After disease progression, patient may experience:

• Low grade fever
• Dizziness
• Irritability
• Night sweats
• Abdominal fullness (Left upper quadrant)
• Bone pain
• Blurred vision

Question 11

What are some laboratory findings associated with Chronic Myelogenous leukemia (CML)?

Answer 11

• WBC elevation – Hallmark sign; 15,000-500,000/microL; frequently 150,000/microL at initial diagnosis; Blasts are usually < 5%
• Presence of BCR/ABL gene detected in peripheral blood using polymerase chain reaction- establishes diagnosis of CML
• Vitamin B12 serum levels are usually elevated ( up to 10x normal limits)
• Lactate dehydrogenase (LDH) and uric acid levels may be elevated
• Philadelphia chromosome- present in peripheral smear and bone marrow
• Low to absent leukocyte alkaline phosphatase (LAP) is a Characteristic Finding; also called neutrophilic alkaline phosphatase (NAP).

Question 12

How do you manage patients with Chronic Myelogenous leukemia (CML)?

Answer 12

• Hematology/oncology referral
• Immediate therapy not indicated unless:
  
  • WBC count < 200,000/microL, OR
  • Evidence indicates:
    
    • Priapism
    • Confusion
    • Venous thrombosis
    • Visual blurring
    • Dyspnea
• Therapy includes tyrosine kinase inhibitor (TKI)
• Hematopoietic stem cell transplant
• Supportive therapy:
  
  • Hydration
  • Allopurinol 100mg tid for hyperuricemia
  • For symptomatic leukocytosis, hydroxyurea or apheresis can be used in addition to TKI
  • For symptomatic thrombocytosis, hydroxyurea, antiaggregants, anagrelide or apheresis can be used.
• Allogenic bone marrow transplant (usually sibling matched) in ONLY curative therapy