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HCR240-Chapter12DisordersofWhiteBloodCells.pptx

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Chapter 12

Disorders of White Blood Cells

Overview

WBC’s (leukocytes) protect against infection

WBC’s produced in bone marrow

Innate Immunity

1st line of defense

Neutrophils, macrophages

Inflammatory response

Adaptive Immunity

Specific and acquired

B and T lymphocytes

Memory cells

Epidemiology

Leukemia

Proliferation of cancerous WBC’s

Specific cell type

90% of leukemia cases are diagnosed in adults

Leukemia is the 3rd most common cancer type in children

Lymphomas

Solid tumors of lymphoid cells

Abnormal proliferation of B and T cells

3% of US population per year

Basic Concepts of WBC Function

Three major categories

Monocytes

Mature into macrophages

Lymphocytes

T and B cells

Granulocytes

Basophil, eosinophil, neutrophil

Neutrophil

Most common granulocyte

AKA: Polymorphonuclear (PMN) cells

Hematopoiesis

Basic Concepts

Pluripotent stem cells give rise to WBC’s, RBC’s, and platelets

Myeloid stem cells

Granulocytes and monocytes

Lymphocyte stem cells: T and B cells

B cells: antibody-producing cells

T cells: CD4 and CD8 cells

“Blast cells”

Immature, precursor cells

Lymphatic System

Agranulocytes

Monocytes

2%–10% of circulating WBC’s

Macrophages

Mature monocytes in tissues

Phagocytosis, cytokine synthesis

Dendritic cells

Antigen-presenting cells

Lymphocytes

20%–40% of circulating WBC’s

T and B cells

Provide long-term immunity

B cells produce antibodies

Immunoglobulins, Igs

Macrophage and Phagocytosis

Granulocytes

Cytoplasm contains granules of chemicals

Cells: basophils, eosinophils, neutrophils

Eosinophils

1%–7% of circulating WBC’s

Elevate during parasitic infections and allergies

Basophils

Less than 2% of circulating WBC’s

Levels elevate during infection and inflammation

Granules contain histamine which, help signal neutrophil migration

Granulocytes (continued)

Neutrophils

40%–80% of circulating WBC’s

First responders, carry out phagocytosis

Release enzymes to destroy microorganisms, releasing free radicals

Polymorphonuclear (PMN’s)

Mature neutrophils

AKA: “Segs”

“Bands”—immature neutrophils

“Shift to the left”

High number of bands, indicating high level of neutrophil formation

Alterations in WBC Number

Leukocytosis

WBC above 11,000 cells/microliter

Leukemoid reaction

WBC above 50,000 cells/microliter

Due to cause other than leukemia

Leukopenia

WBC less than 4,000/microliter

Neutrophils most commonly affected

Alterations in WBC Number (continued_1)

Neutrophilia

Most common WBC to elevate in leukocytosis

Neutrophil count greater than 7,000/microliter

With total WBC less than 11,000

Very common in response to bacterial infections, inflammation

Smoking elevates neutrophil number

May play a role in inflammation associated with smoking

Alterations in WBC Number (continued_2)

Neutropenia

Less than 1,500 neutrophils/microliter

Compromises immune response

Several causes

Medications, including chemotherapy, may cause neutropenia

Filgrastim (Neupogen)

Stimulates neutrophil synthesis

Alterations in WBC Number (continued_3)

All WBC types can present with abnormal numbers

Examples: monocytopenia, eosinophilia, basopenia, etc.

Lymphocytes

Standard values vary with age

Thymus-derived T cells decrease in number as person ages

Hematologic Neoplasms

Leukemia

Neoplastic proliferation of blood cells

Lymphoma

Proliferation of B or T lymphocytes in lymphoid tissue

Risk factors

Anything that damages the DNA

Some viruses predispose: EBV, HIV

H. pylori infections have been associated with lymphoma

Hematologic Neoplasms (continued_3)

Symptoms

Anemia

Leukopenia (dysfunctional WBC’s)

Thrombocytopenia (bleeding and bruising)

Bone pain (proliferating cancerous blood cells put pressure in marrow of bones)

Enlarged lymph node

Splenomegaly

Hematologic Neoplasms (continued_4)

Diagnosis

CBC with Differential (to determine specific WBC types)

Bone marrow aspiration

Fluorescence in-situ hybridization

Polymerase chain reaction (PCR)

Flow cytometry

Hematologic Neoplasms (continued_5)

Treatment

Chemotherapy

Monoclonal antibodies

Attack tumor antigens

Supply of genetically engineered antibodies specific for tumor antigens

Radiation

Alone or with chemotherapy

External or internal application of radiation

Hematologic Neoplasms (continued_6)

Treatment

Stem cell transplants

Completely or partially ablate patient’s bone marrow, replace with healthy stem cells

Allogenic hematologic stem cell transplant

Matched donor

Autologous hematologic stem cell transplant

Healthy cells from patient

CAR-T cell cancer immunotherapy

Harvest patient T cells, genetically engineered to target cancer antigens

Chimeric antigen-receptor mediated T cells (CAR-T)

Hematologic Neoplasms (continued_7)

Treatment complications

Tumor lysis syndrome

Rapid cell lysis, releasing uric acid, potassium, and phosphate

Differentiation syndrome

Leukemia cells release substances into blood leading to fever, dyspnea, fluid build up around heart and lungs; temporarily stop treatment

Cytokine release syndrome (CRS)

Fever, hemodynamic instability resulting from T-cell targeting therapies and cytokine release

Acute Lymphoblastic Leukemia (ALL)

Aggressive, more common in children than adults (survival rate is over 80% for children)

The faster the response to treatment the better the prognosis

Many chromosomal and genetic alterations

Ph chromosome

Immature T or B cells (lymphoblasts)

Bone marrow lymphoblast of greater than 20% of WBC’s

Acute Lymphoblastic Leukemia (ALL) (continued)

Signs and symptoms

May be nonspecific, anemia, increased bleeding, lymph node enlargements, splenomegaly, increased infection risk, bone pain

May migrate to CNS

Treatment

Chemotherapy, bone marrow transplant, CAR-T

Almost all patients obtain remission

Follow-up maintenance critical to prevent relapse

Chronic Lymphocytic Leukemia (CLL)

Most common leukemia type in US

Individuals over 70 years of age

Etiology

Any agent that can disrupt DNA

Occupational history important

Zeta-chain-associated protein tyrosine kinase 70 (ZAP-70)

Positive: indicates worse prognosis

Negative: better prognosis

Chronic Lymphocytic Leukemia (CLL) (continued_1)

B cell malignancy

B-CLL cells: express proto-oncogene bcl2 allowing constant proliferation

Do not synthesize functional Igs

Typical signs and symptoms of leukemia

Diagnosis

Lymphocytosis with WBC greater than 20,000/microliter

Bone marrow biopsy: “smudge cells”—abnormal lymphocytes

Chronic Lymphocytic Leukemia (CLL) (continued_2)

Treatment depends on stage of cancer

United States: Rai staging

Chemotherapy

Purine analogs, alkylating agents, monoclonal antibody agents

Radiation

Non-ablative stem cell therapy

Complication: Richter’s transformation

CLL changes to aggressive type of lymphoma

Lymphoma Overview

HL (previously called Hodgkin’s disease)

Most common in ages 15 to 20 years and over 50 years of age

~20% of the lymphomas

B cell: Reed-Sternberg cells (“owl eyes”)

5 subtypes

NHL (Non-Hodgkin’s Lymphoma)

Over 80% of lymphoma cases; more common in older individuals

B or T cells or NK cells

30 subtypes

Lymphomas

Staging

Size

Spread

Microscopic appearance

Genetic markers

“Bulky” and “nonbulky” (better prognosis)

Non-Hodgkin’s Lymphoma (NHL)

B, T, or NK cells

Middle aged or older adults; more common in men

Chromosomal translocations (chromosomes 14 and 18)

Some pathogens (HIV, Hep C, H. pylori) associated with NHL development

Immunosuppressive treatment may increase NHL risk

Non-Hodgkin’s Lymphoma (NHL) (continued)

Enlarged, painless lymph node is often first sign

Diagnosis

Lymph node biopsy

Treatment

Chemotherapy (CHOP)

Immunotherapy

Radiation

Surgery

Hodgkin’s Lymphoma (HL)

B cell

Most common lymphoma in young adults and children over 10 years of age

Unknown cause, but EBV may play a role

Diagnosis

Reed-Sternberg cells

Malignant B cell with two nuclei (appear as owl eyes)

Lymph node biopsy

Immunohistochemistry to determine cell surface markers

Hodgkin’s Lymphoma (HL) (continued)

Signs and symptoms

No dramatic symptoms

Enlarged lymph node may be present

Treatment

Combination chemotherapy, radiation, immunotherapy

MOdule 6 disc

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