White Blood Cell Disorders(old)

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

Leukemia

proliferation of cancerous WBCs; it can arise from a specific WBC cell type.

What is the age distribution of leukemia?

About 90% of leukemia cases occur in adults; leukemia is the 3rd most common cancer in children.

Lymphoma

Solid tumors of lymphoid cells

T and B cells

Hodgkin’s vs Non-Hodgkin’s

Myelodysplastic syndrome (MDS)

Dysplastic development of one or more stem cell in bone marrow

Multiple myeloma

Excessive proliferation of plasma cells (derived from B lymphocytes)

Secrete immunoglobulins (Igs)

3 major categories of WBCs

Monocytes

Lymphocytes

Granulocytes

Monocytes

Mature into macrophages

Also categorized as an agranulocyte

Lymphocytes

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

thymus

Where are b lymphocytes processed

bone marrow

Myeloid stem cells potential

Can become monoblast, myeloblast, megakaryoblast, Erythroblast

Myeloblasts final form

Basophils, Eosinophils, neutrophils

Monoblasts next form

monocytes

Megakaryocytes turn into???

Megakaryocytes that turn into thrombocytes

Erythroblasts turn into???

Reticulocytes that become erythrocytes

T cells variants

CD4 and CD8

“blast cells'“

immature, precursor cells

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

Dendritic cells

Antigen presenting cell

T and B cells

Provide long-term immunity

Memory cells

B cells produce antibodies

Immunoglobulins, Igs

Cytoplasm contains…

Granules of chemicals

When do eosinophils

Elevate during parasitic infections and allergies

Basophils

Elevate during infection and inflammation

Neutrophils

First responders

‒ Carry out phagocytosis

‒ Release enzymes to destroy microorganisms

‒ Free radicals formation

Polymorphonuclear (PMNs)

Another name for mature neutrophils aka segs

Immature neutrophils

bands

“shift to the left”

high number of bands indicating increased neutrophil formation

Leukocytosis range

WBC above 11,000 cells/microliter

Leukopenia range

WBC less than 4,000/microliter

Leukopenia most affected cell

Neutrophils most commonly affected

Leukomoid reaction range

WBC above 50,000 cells/microliter

Leukomoid reaction is NOT due to _______

leukemia

other wbc abnormalities examples

Monocytopenia, eosinophilia, basopenia, etc

Lymphocytes ranges

Standard values vary with age

Thymus-derived T cells decrease as person ages

Neutrophilia

Increase in neutrophils, most common WBC to elevate in leukocytosis

Neutrophilia range

>7,000 neutrophils/µL (with total WBC <11,000/µL).

Neutrophilia causes

Common response to

bacterial infections

inflammation

Smoking related inflammation

Smoking elevates neutrophil number

May play a role in smoking related inflammation

Neutropenia

decreased neutrophils

Neutropenia range

<1,500/µL

Neutropenia and the immune response

Compromises immune response

Neutropenia causes examples

several causes but medications such as chemotherapy can cause it

Treatment of neutropenia

Filgrastim (Neupogen), which stimulates neutrophil production.

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 a left shift typically indicate?

Increased inflammation or bacterial infection

I ratio

Immature neutrophils to total neutrophils

What does myelodysplastic syndrome affect?

Bone marrow stem cells

Reduces RBCs, WBCs, and/or platelets

Who is affected by myelodysplastic

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

What treatments may be used for high-risk MDS?

Erythropoiesis-stimulating agents

blood transfusions

lenalidomide (Revlimid)

stem cell transplant

Diagnosing

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 infections: lymphoma

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;

temporarily stop treatment

Cytokine release syndrome (CRS)

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

Acute Lymphoblastic Leukemia (ALL)

Aggressive leukemia

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 of greater than 20% of WBCs

Genetic abnormalities in ALL

ALL can involve many different genetic abnormalities

EX: Ph chromosome.

Signs and symptoms of ALL

Anemia

increased bleeding

lymph node enlargement

splenomegaly

increased infection risk

and bone pain

AIL SIA(or SIB)

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

Treaments for ALL

chemotherapy

bone marrow transplant

CAR-T

monoclonal antibodies

Tyrosine kinase inhibitors(TKIs)

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

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