True or False: All red blood cells, white blood cells and platelets are derived from a single pluripotential cell?

True

What is the numerical definition of neutropenia?

< 1500 neutrophils per microliter (cells/μl)

What is the numerical definition of agranulocytosis?

< 200 neutrophils per microliter (cells/μl)

What are the two basic mechanisms that cause neutropenia?

1.    Decreased production of neutrophils

2.   Increased destruction of neutrophils

What are specific causes of decreased production of neutrophils?

·        Aplastic anemia

·        Irradiation

·        Infiltrative tumors of the bone marrow - leukemia, lymphomas

·        Drugs- Cytotoxic drugs

What are specific causes of increased destruction of neutrophils?

·        Increased destruction in spleen in splenomegaly  

·        Increased destruction in spleen in Felty syndrome

·        Idiosyncratic drug reactions

Which drugs cause dose related neutropenia/pancytopenia?

·        Alkylating agents

·        Antimetabolites

Which drugs cause neutropenia as an idiosyncratic reaction?

·        Chloramphenicol

·        Phenothiazines

·        Thiouracils

·        Phenylbutazones

How does the host fight EBV?

Both cell and humoral (aka antibody) mediated immunity

What is the effect of neutropenia?

Ulcerated mucocutaneous lesions of the mouth, skin, vagina, GI tract, and respiratory tract that can lead to sepsis and death.

What is the treatment of neutropenia?

·        Antibiotics

·        GM-CSF (neupogen)

What is the infectious agent that causes mononucleosis?

Epstein-Barr virus (EBV)

Which patient population is most often affected by EBV?

Adolescents and young adults

How is EBV transmitted?

Saliva

Which host cells become infected with EBV?

Oral pharyngeal B lymphocytes

What is the total duration of infection with EBV (prodromal plus acute period)?

4 to 8 weeks

What is the duration of the acute phase of EBV?

2-3 weeks

What are the symptoms of the acute phase of EBV?

·        Fever

·        Pharyngitis

·        Lymphadenopathy of cervical, axillary and 

          inguinal nodes

·        Low grade hepatitis characterized by mild   

          elevation of transaminases

·        Splenomegaly

What is the typical WBC count of EBV infection?

12000 to 18000 with 60% lymphocytes many of which are atypical lymphocytes

What is the histologic name of the cell that is pathopneumonic for Hodgkins lymphoma?

Reed-Sternberg cell

What is the epidemiology of Hodgkins lymphoma?

Bimodal incidence with one peak mid 20 years of age and second peak mid 50 years of age

What is the most common presentation of Hodgkins lymphoma?

Painless lymphadenopathy

What sites are affected in wide-spread Hodgkins lymphoma?

·        Bone marrow

·        Spleen

·        Liver

·        GI tract

·        Lungs

·        Central nervous system

Which lymph nodes are most commonly affected with Hodgkins lymphoma?

·        Cervical nodes

·        Mediastinal nodes

What are type B symptoms of Hodgkins lymphoma?

·        Fever

·        Night sweats

·        Chills

·        Weight loss

How is a diagnosis of Hodgkins lymphoma made?

1.    Lymph node biopsy

2.   CT scan of chest, abdomen and pelvis for staging purposes

3.   Bone marrow biopsy if bone marrow involvement suspected

What are the stages of Hodgkins lymphoma?

1.    Stage 1: Node involvement limited to a single area

2.   Stage 2: Node involvement in adjacent areas

3.   Stage 3: Node involvement on both sides of the diaphragm

4.   Stage 4: Diffusely disseminated disease

How is Hodkins lymphoma treated?

·        Radiation therapy

·        Chemotherapy

How more common is non-Hodgkins lymphoma (NHL) than Hodgkins lymphoma?

Three times more common

What percentage of NHL are B cell origin?

80-85%

How does NHL most often present?

Painless lymphadenopathy

How can the spread of NHL differ from Hodkins lymphoma?

NHL can be noncontiguous

What is the treatment of NHL?

·        Early stages: Radiation therapy

·        Late stages: Radiation plus chemotherapy

·        B cell NHL: Rituximab

Which patient population is most often affected by acute lymphocytic leukemia?

Age 4-6 year old

What type of cells most commonly make up acute lymphocytic leukemia?

Pre B cell origin

Which patient population is most often affected by acute myelogenous leukemia?

Ages 60-65 year old

Which cell line make up acute myelogenous leukemia?

No particular predominant cell type more heterogenous some arise from myeloblasts others myelocyte-granulocyte precursors

Which chromosomal abnormality is associated with acute myelogenous leukemia?

Down’s syndrome

How do both types of acute leukemia manifest?

·        Rapid onset

·        Fever

·        Bleeding from thrombocytopenia

·        Bone pain

·        Generalized lymphadenopathy

·        Splenomegaly

·        Hepatomegaly more in (ALL)

What are the symptoms with central nervous system involvement with both types of acute leukemia?

·        Headache

·        Vomiting

·        Cranial nerve palsies

more CNS effects seen in (ALL) than (AML)

What is leukostasis?

Impaired blood flow in the microcirculation due to high WBC count

At what WBC count does leukostasis occur?

Above 100,000

Which organs are most often affected by leukostasis?

·        Lungs

·        Brain

What blood test is elevated from rapid cell turnover seen in both types of acute leukemia?

Uric acid

What is the prognosis of acute lymphocytic leukemia (ALL)?

80% of children with ALL are cured

What is the prognosis of acute myelogenous leukemia (AML)?

30-40% achieves long term disease free survival

How is acute leukemia diagnosed?

·        Identification of blast forms on peripheral blood smear

·        CT for staging

·        Lumbar puncture to assess for CNS involvement

What are the two types of chronic leukemia?

1.    Chronic lymphocytic leukemia

2.   Chronic myelocytic leukemia

What is the epidemiology of chronic lymphocytic leukemia?

Older patients > 50 years old

Which lymphocytes are involved most often in lymphocytic leukemia?

B cells

How do patients with chronic lymphocytic leukemia present most frequently?

Asymptomatically with incidentally noted elevated WBC count on CBC

For patients with symptomatic chronic lymphocytic leukemia what symptoms do they present with?

·        Fatigue

·        Weight loss

·        Lymphadenopathy

·        Splenomegaly

·        Autoimmune (Coombs positive) hemolytic anemia

·        Thrombocytopenia

·        Recurrent infections

What is the prognosis of chronic lymphocytic leukemia?

Good – many patients live greater than 10 years after diagnosis

What percentage of leukemia patients has chronic myelogenous leukemia?

15-20%

What is the epidemiology of patients with chronic myelogenous leukemia?

Usual age 30-50 years old

What is the classic histopatholgic finding in patients with chronic myelogenous leukemia?

Philadelphia chromosome

What is a Philadelphia chromosome?

It is a translocation of chromosome 9 with chromosome 22. Forming a BCR-ABL hybrid gene.

What are the three phases of the triphasic course in patients with chronic myelogenous leukemia?

1.    Chronic phase

2.   Short term accelerated phase

3.   Terminal blast crisis

 What are the characteristics of the chronic phase of chronic myelogenous leukemia?

·        Asymptomatic

·        Weakness

·        Weight loss

·        Abnormal CBC: leukocytosis, anemia, thrombocytopenia

What are the characteristics of the short accelerated phase of chronic myelogenous leukemia?

·        Splenomegaly

·        Fever

·        Night sweats

·        Bone pains

·        Weight loss

·        Bleeding

How long does the short accelerated phase of chronic myelogenous leukemia typically last?

6 to 12 months

How is the blast crisis phase of chronic myelogenous leukemia characterized?

Conversion to acute leukemia

What is the prognosis of a patient with chronic myelogenous leukemia in blast crisis?

Poor

How is chronic myelogenous leukemia treated?

With the medication Gleevac

What is the mechanism of action of Gleevac, which is used to treat chronic myelogenous leukemia?

It inhibits BCR-ABL oncogene

What is the most common plasma cell dyscrasia?

Multiple myeloma

What is the epidemiology of multiple myeloma?

Patients greater than 60 years old

What cell line is involved in multiple myeloma?

Clonal proliferation of a defective plasma cell within the bone marrow

How are the clones of the defective plasma cell detected?

By performing a bone marrow biopsy – if greater than 10% of the cells seen in the bone marrow are plasma cells, this is indicative of multiple myeloma

What do the clones of the defective plasma cell produce?

M protein

What is M protein?

A specific immunoglobulin (aka antibody) that is produced in excessive amounts

Which subclass of immunoglobulins most often makes up the M protein?

IgG (60%) followed by IgA

How is the M protein detected?

By performing electropheresis of the plasma of the affected patient, a M spike will be detected.

How often is the M protein only made up of the light chain portion of immunoglobulins?

15-20% of multiple myeloma cases

In these cases where the M protein is exclusively made up of light chains why are they not detected when performing plasma electropheresis?

Because they are readily excreted into the urine and therefore do not accumulate in the plasma. These light chains that are excreted in the urine are called Bence Jones proteins. More commonly, however, malignant plasma cells produce both complete immunoglobulins and free light chains; therefore, both M proteins and Bence Jones proteins are present. 

What test should be ordered to detect light chains in the urine?

Urine protein electropheresis

What is the name given to the light chains in the urine in multiple myeloma?

Bence-Jones proteins

What are the clinical manifestations of multiple myeloma?

·        Bone pain

·        Pathologic fracture

·        Anemia

·        Renal insufficiency

·        Recurrent infections

Which bones are most commonly affected in multiple myeloma?

·        Vertebra

·        Ribs

·        Skull

·        Pelvis

·        Femur

What is the median survival of multiple myeloma?

4-5 years

How is a diagnosis of multiple myeloma made?

1.    Bone marrow biopsy demonstrating > 10% plasma cells

2.   Radiographic skeletal survey that demonstrates lytic lesions in the affected bone

3.   Detection of M spike in the plasma or Bence-Jones proteins in the urine on protein electropheresis