White Blood Cells Study Guide Cut

Apoptosis

Programmed Cell Death

Neoplasia

Abnormal, uncontrolled cell growth

Anaplasia

Loss of normal cell differentiation and structure

Metaplasia

Change from one cell type to another

WBCs (Leukocytes)

Protect against infection

Three major categories of cell types

Bone Marrow

Produces WBCs

Also produces RBCs and platelets

Innate immunity

1st line of defense

Neutrophils, macrophages

Inflammatory response

Adaptive immunity

Specific and acquired

B and T lymphocytes

Memory cells

3 major categories of WBCs

Monocytes

Lymphocytes

Granulocytes

Monocytes

Mature into macrophages

Also categorized as an agranulocyte

Lymphocyte

T and B cells

Also categorized as an agranulocyte

Granulocytes

Basophil, eosinophil, neutrophil

Most common granulocyte

Neutrophil!

Hematopoieis

process of blood cell formation

Root of hematopoiesis

Pluripotent stem cell in the bone marrow, can differentiate into myeloid or lymphatic stem cells

Lymphatic stem cells potential

Become lymphoblasts that become B or T lymphocytes

Where are T lymphocytes processed and where are B lymphocytes processed

T - Thymus

B- Bonemarrow

Myeloid stem cells potential

Can become:

monoblast

myeloblast

megakaryoblast

Erythroblast

Myeloblasts final form

Basophils, Eosinophils, neutrophils

Monoblasts next form

monocytes

Megakaryoblasts turn into???

Megakaryocytes that turn into thrombocytes(AKA platelets)

Erythroblasts turn into???

Reticulocytes that become erythrocytes

Neutrophil CBC composition

40–80% (1,500–8,000/μL)

Lymphocytes CBC composition

20–40% (1,000–4,000/μL)

Monocytes CBC composition

2–10% (200–1,000/μL)

Eosinophils CBC composition

1–7% (0–500/μL)

Basophils CBC composition

<2% (0–200/μL)

Macrophages

Mature monocytes in tissues

Phagocytosis

Cytokine synthesis

What do neutrophils fight?

Fights bacterial and fungal infections

What do lymphocytes fight?

viral infections

What do eosinophils fight?

Parasitic infections, also trigger allergic reactions

What do basophils do

Releases histamines during allergic reactions and heparin(anticoagulant)

Neutrophils

First responders

‒ Carry out phagocytosis

‒ Release enzymes to destroy microorganisms

‒ Free radicals formation

Polymorphonuclear cells (PMNs)

Another name for mature neutrophils aka segs

Immature neutrophils

bands

“shift to the left”

high number of bands indicating increased neutrophil formation

What band percentage is considered a significant left shift?

over 16% of total neutrophils

What absolute band count indicates a notable left shift?

>1,500 bands/mm³.

What does myelodysplastic syndrome affect?

Bone marrow stem cells

Reduces RBCs, WBCs, and/or platelets

Who is affected by myelodysplastic syndrome

Median age of diagnosis: >70 years

Etiology of MDS

Environmental exposure, radiation, benzene

Secondary MDS

Develops in response to cancer treatments

Clinical presentation of MDS

Anemia

increased bruising

increased infections

Low Risk MDS

Mild cytopenia, often asymptomatic, and may require no treatment.

High risk MDS

More severe/progressive disease with risk of acute myelogenous leukemia (AML) or complete bone marrow failure

MDS possible treatments

Erythropoiesis-stimulating agents

blood transfusions

lenalidomide (Revlimid)

stem cell transplant

Diagnosing MDS

Peripheral blood (PB) smear

bone marrow aspirate and biopsy,

Persistent cytopenia and dysplasia

Hematological Neoplasms Risk Factors

DNA damaging agents and infections

DNA damaging agents examples

Radiation

Benzene

Infections(viral) examples

HPV and EBV

Infections(bacteria) examples

H. Pylori (increased lymphoma risk)

What is the Philadelphia (Ph) chromosome?

A chromosome abnormality caused by a translocation between chromosomes 9 and 22.

What does the Philadelphia chromosome activate?

Tyrosine kinase, which promotes abnormal cell growth.

How can the Philadelphia chromosome be treated?

Tyrosine kinase inhibitors (TKIs) can inhibit the abnormal tyrosine kinase activity.

Leukemia does NOT typically involve what cell type

Typically does not involve lymphocytes

Lymphoma

Cancerous Lymphocytes; solid tumor

More common than leukemia

Similarities between leukemia and lymphoma

Nonfunctional, cancerous WBCs proliferate and overwhelm the bone marrow and other lymphoid tissue.

Hematological Neoplasms signs and symptoms

• Anemia

• Increased infection (dysfunctional WBCs)

• Thrombocytopenia (bleeding and bruising)

• Bone pain (proliferating cancerous blood cells

put pressure in marrow of bones)

• Enlarged lymph node

Hematological Neoplasms Diagnosis

CBC differential

Bone marrow aspiration

Cytogenic testing
PCR

Hematological Neoplasms Treatment

• Chemotherapy

• Monoclonal antibodies

• Radiation

• Bone marrow stem cell transplant

• CAR-T cell therapy

Car-T cell therapy

Chimeric antigen-receptor mediated T cells

Hematological Neoplasms Treatment Complications

Tumor Lysis Syndrome

Differentiation Syndrome

Cytokine release Syndrome

Tumor lysis syndrome

Rapid cell lysis causes release of uric acid, potassium, and phosphate

Differentiation syndrome

Leukemia cells release substances into blood leading to:

fever

dyspnea

fluid build up around heart and lungs;

need to temporarily stop treatment

Cytokine release syndrome (CRS)

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

Who is Acute Lymphoblastic Leukemia most common in?

More common in children

Survival rate >80% for children

Cells involved in ALL

Immature T or B cells (lymphoblasts)

What bone marrow finding is diagnostic of ALL?

Bone marrow lymphoblast comprising greater than 20% of WBCs

Genetic abnormalities in ALL

ALL can involve many different genetic abnormalities

EX: Ph chromosome.

ALL sign not included in the general signs

Spenomegaly

Why can ALL cause anemia, bleeding, and increased infection risk?

Leukemic lymphoblasts crowd the bone marrow → suppress normal RBC, platelet, and WBC production

Can ALL spread outside the bone marrow?

Yes. ALL can migrate to the CNS (central nervous system).

ALL Treatment phases

prephase, induction, consolidation, and maintenance

Why is maintenance therapy and follow-up important in ALL?

to prevent relapse after remission(which almost all patients obtain)

Chronic Lymphocytic Leukemia (CLL)

Most common leukemia type in United States involving abnormal B lymphocytes

Who is most commonly affected by CLL?

Older adults

especially those >70 years old

it is more common in males and people with a family history

CLL etiology

Any agent that can disrupt DNA

Important to consider occupational history

How does CLL typically present?

Can cause typical leukemia signs and symptoms

but 25–50% of patients are asymptomatic

What WBC finding may suggest CLL?

WBC >20,000/μL, with >5,000 B-lymphocytes/μL in peripheral blood for at least 3 months.

Immunophenotyping

uses specialized antibodies to identify and classify cells

What is immunophenotyping used for in CLL?

To identify B-CLL cells by their CD antigens.

Why are CD antigens important in CLL?

They have prognostic and therapeutic implications.

Clinical Staging Systems for CLL

Rai and Binet

CLL complication example

Richter’s transformation

CLL changes to aggressive type of lymphoma

Life expectancy after CLL diagnosis

Life expectancy 2-20 years

Acute Myleogenous Leukemia

Fast-growing cancer of the bone marrow that affects myeloid cells

What bone marrow finding is characteristic of AML?

≥20% myeloblasts in the bone marrow

Can AML myeloblasts spread outside the bone marrow?

Yes. Myeloid blasts can invade tissues such as the skin, lungs, spleen, and liver.

What factors increase the risk of AML?

Previous chemotherapy or radiation

genetic/environmental factors

and activation of oncogenes such as FLT3 and c-KIT

Signs and symptoms of AML

Typical signs and symptoms of leukemia

Diagnosis of AML

CBC with differential, bone marrow biopsy, FISH, and PCR

Chromosomal abnormality of AML

Genetic translocation chromosome 8 and 12

two standard chemotherapy stages for AML

Remission induction and consolidation

Goal of remission induction therapy in AML

achieve remission by reducing/eliminating detectable leukemia cells

purpose of consolidation therapy in AML

To eliminate remaining leukemia cells and reduce the risk of relapse after remission

What is leukapheresis used for in AML?

Uses machine that filters blood to rapidly reduce an abnormally high white blood cell count

What targeted/biological therapies may be used to treat AML?

Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies

What cells are involved in Chronic Myelogenous Leukemia(CML)

Mature, dysfunctional myeloid cells

What chromosome abnormality is found in about 95% of adults with CML?

Philly(Philadelphia) Chromosome

CML Population most affected

Age 65 years or older