Neutropenia is a decrease in neutrophil counts in the bloodstream below normal levels. It makes patients highly susceptible to bacterial and fungal infections. The most common causes are chemotherapy and immunosuppressive drugs that decrease bone marrow function. Symptoms can range from minor to life-threatening and include fever, sore throat, mouth sores, and pneumonia. Treatment involves administering antibiotics, antifungals, and hematopoietic growth factors to boost neutrophil production. Protective measures like handwashing are also important for neutropenic patients.

1. Neutropenia

3. Introduction
• Leukopenia refers to a decrease in the total WBC count (granulocytes,
monocytes, and lymphocytes).
• Granulocytopenia is a deficiency of granulocytes, which include
neutrophils, eosinophils, and basophils.
• A reduction in neutrophils is termed neutropenia
(The neutrophilic granulocytes (neutrophils), which play a key role in
phagocytizing pathogenic microbes, are closely monitored in clinical
practice as an indicator of a patient’s risk for infection.)

4. • The absolute neutrophil count (ANC) is determined by multiplying the
total WBC count by the percent of neutrophils.
• Neutropenia is defined as ANC less than 1000 cells/µL (1 × 10 9 /L).
Normally, neutrophils range from 2200 to 7700 cells/µL.
• Severe neutropenia is defined as an ANC less than 500 cells/µl

5. Causes
Autoimmune Disorders
Felty syndrome
Systemic lupus erythematosus
Drugs
Alkylating agents (busulfan)
Antiinflammatory drugs (indomethacin)
Antimetabolites (methotrexate, mercaptopurine, cytarabine)
Antimicrobial agents (ganciclovir, penicillin G, trimethoprim/sulfamethoxazole)
Antitumor antibiotics (daunorubicin, doxorubicin)
Cardiovascular drugs (captopril, procainamide)
Diuretics (hydrochlorothiazide)
 Miscellaneous (ticlopidine, penicillamine)

6. Continued..
Hematologic Disorders
 Aplastic anemia
Congenital (cyclic neutropenia)
Fanconi syndrome (a defect of proximal tubule leading to
malabsorption of various electrolytes and substances)
Idiopathic neutropenia
Leukemia
Myelodysplastic syndrome

7. • Infections
• Fulminant bacterial infection (e.g., typhoid fever, miliary tuberculosis)
• Parasitic
• Rickettsial
• Viral (e.g., hepatitis, influenza, HIV, measles)

8. Continued..
Others
• Bone marrow infiltration (e.g., carcinoma, tuberculosis, lymphoma)
• Hemodialysis
• Hypersplenism
• Nutritional deficiencies (cobalamin, folic acid)
• Severe sepsis
The most common cause of neutropenia: chemotherapy and
immunosuppressive therapy
A term we use to describe the lowest point of neutropenia (and other blood
cells) in a patient treated with chemotherapy is nadir

9. Clinical features
• The patient with neutropenia is predisposed to infection with
opportunistic pathogens and nonpathogenic organisms from the
normal body flora.
• The classic manifestations of inflammation—redness, heat, and
swelling—may not occur.
• WBCs are the major component of pus. Therefore, in the patient with
neutropenia, pus formation (e.g., as a visible skin lesion or as lung
infiltrates on a chest x-ray) is absent.
• Minor infections can lead rapidly to sepsis and death.

10. Continued..
• Common entry points for pathogenic organisms in susceptible host:
The mucous membranes of the throat and mouth, skin, perineal area,
and pulmonary system are
• Sore throat and dysphagia, ulcerative lesions of the pharyngeal and
buccal mucosa, diarrhea, rectal tenderness, vaginal itching or
discharge, shortness of breath, and nonproductive cough.
• Any report of minor pain or any other symptom by the patient may be
significant and should be reported to the HCP at once.
• These seemingly minor problems can progress to fever, chills, sepsis,
septic shock, and death if not recognized and treated early

11. Diagnostic evaluation
• The primary diagnostic tests for assessing neutropenia are the
peripheral WBC count and bone marrow aspiration and biopsy.
• A differential count can confirm the presence of neutropenia
(Absolute neutrophil count less than 1000/µL [1 × 10 9 /L]).
• If the differential WBC count reflects an absolute neutropenia of 500
to 1000/µL (0.5 to 1.0 × 10 9 /L), the patient is at moderate risk for a
bacterial infection.
• An absolute neutropenia of less than 500/µL (0.5 × 10 9 /L) places the
patient at severe risk.

12. Continued..
• A peripheral blood smear assesses for immature forms of WBCs (e.g.,
bands).
• The hematocrit level, reticulocyte count, and platelet count are done to
evaluate bone marrow function
• bone marrow aspiration and biopsy is done to
• examine cellularity and cell morphology.
• Other studies may be done to assess spleen and liver function.

13. Continued..
• Cultures of sputum, throat, lesions, wounds, urine, and feces may part
of patient surveillance.
• Monitor the neutropenic patient for signs and symptoms of infection
(e.g., any fever 100.4°F [38°C] or greater) and early septic shock.
• Early identification of a potentially infective organism depends on
obtaining cultures from various sites.
• Serial blood cultures (at least 2) or 1 from a peripheral site and 1 from a
venous access device should be done promptly and antibiotics started
within 1 hour.
• Depending on the clinical situation CT scans, bronchoscopy with
bronchial brushings, or lung biopsy to diagnose the cause of
pneumonic infiltrates

14. Management: components
• Determining the cause of the neutropenia
• Instituting antibiotic therapy promptly
• Identifying the offending organisms if an infection has developed,
• Hematopoietic growth factors prophylactically after chemotherapy,
• Implementing protective practices (e.g., strict hand washing, skin and
oral hygiene)

15. Antibiotic therapy
• Giving broad-spectrum antibiotics is usually by the IV route because of
the rapidly lethal effects of infection.
• Some oral antibiotics are highly effective and routinely used for
prophylaxis against infection in some neutropenic patients.
• The use of a third- or fourth-generation cephalosporin with broad
microorganism coverage (e.g., cefepime, ceftazidime) or a carbapenem
(e.g., imipenem/cilastatin [Primaxin]) will be started and augmented

16. Antifungal
• The longer the neutropenia, the greater the risk is for a fungal
infection.
• Antifungal therapy is started whenever a culture is positive, or in
patients who do not become afebrile with broad-spectrum antibiotic
coverage.

17. Continued..
• Myeloid growth factors can be used to prevent neutropenia or to reduce
its severity and duration.
• (Factors [Neupogen (filgrastim), Granix (tbo-filgrastim),
Sargramostim (leukine))
• Once neutropenia has occurred, these agents are generally not as
effective
• Hand washing is the single most important preventive measure to
minimize the risk for infection in the neutropenic patient.
• Strict hand washing by staff and visitors using an antiseptic hand wash
before and after contact is the major method to prevent transmission of
harmful pathogens.

18. Continued..
• Separate immunocompromised patients from those who are infected
or have conditions that increase the probability of transmitting
infections (e.g., poor hygiene caused by lack of understanding or
cognitive dysfunction).
• If the patient is hospitalized, a private room should be used.
• High-efficiency particulate air (HEPA) filtration is an air-handling
method with a high-flow filtering system that can reduce or eliminate
the number of aerosolized pathogens in the environment .
• (used for hematopoietic stem cell transplant patients)

19. High efficiency particulate filter

20. Patient teaching
• WASH YOUR HANDS frequently and make sure those around you wash their
hands frequently, especially if they help with your care.
• You may also use an antibacterial hand gel.
• Notify your nurse or HCP if you have any of the following: Fever ≥100.4°F
(38°C) ∗( Chills or feeling hot Redness, swelling, discharge, or new pain on or
in your body Changes in urination or bowel movements Cough, sore throat,
mouth sores, or blisters
• If you are at home, take your temperature as directed and follow instructions
on what to do if you have a fever.
• Avoid crowds and people with colds, flu, or infections.
• If you are in a public area, wear a mask and use hand sanitizing gel frequently.
• Avoid uncooked meats, seafood, or eggs and unwashed fruits and
vegetables.
• Ask your HCP about specific dietary guidelines for you

21. Continued..
• Bathe or shower daily.
• Use a moisturizer to prevent skin from drying and cracking.
• Maintain some daily activity as instructed by your health care team.
• This may include walking and moderate exercise while avoiding
crowds.
• Brush your teeth with a soft toothbrush 4 times daily.
• You may floss once daily if it does not cause excessive pain or
bleeding.
• Avoid alcohol-based mouthwashes.
• Do not garden or clean up after pets.
• You may feed and pet your dog or cat if you wash your hands well
after handling.

22. Leukemia
• Leukemia is the general term used to describe a group of cancers
affecting the blood and blood-forming tissues of the bone marrow,
lymph system, and spleen.
• Leukemia occurs in all age-groups.
• It results in an accumulation of dysfunctional cells because of a loss of
regulation in cell division.

23. Etiology
• Leukemia, begin as a mutation in the DNA of certain cells. (CEBPA)
genes. CCAAT enhancer binding protein alpha (cytosine-
cytosine-adenosine-adenosine-thymidine)
• Most leukemias result from a combination of factors, including
genetic and environmental influences.
• Abnormal genes (oncogenes) can cause many types of cancers,
including leukemias.
• Chemical agents (e.g., benzene), chemotherapeutic agents (e.g.,
alkylating agents, topoisomerase II inhibitors), viruses, radiation, and
immunologic deficiencies have all been associated with the
development of leukemia.
• Depending on the type of leukemia, other potential causes are
exposure to pesticides (farmworkers), smoking, and obesity

24. Classification

25. • Leukemia is classified based on acute versus chronic disease and on
the type of WBC involved.
• The terms acute and chronic refer to cell maturity and nature of
disease onset.
• Acute leukemia is characterized by the clonal proliferation of
immature hematopoietic cells

26. Acute myeloblastic leukemia
• AML represents about one third of all leukemias, and it makes up
about 80% of the acute leukemias in adults.
• Its onset is often abrupt and dramatic.
• A patient may have serious infections and abnormal bleeding from
the onset of the disease.
• AML is characterized by uncontrolled proliferation of myeloblasts, the
precursors of granulocytes.
• There is hyperplasia of the bone marrow.
• The manifestations are usually related to replacement of normal
hematopoietic cells in the marrow by leukemic myeloblasts and, to a
lesser extent, to infiltration of other organs and tissue

27. Acute Lymphocytic Leukemia
• ALL is the most common type of leukemia in children and accounts
for about 20% of acute leukemia cases in adults.
• In ALL, immature small lymphocytes proliferate in the bone marrow.
Most are of B-cell origin.
• Most patients have fever at the time of diagnosis.
• Signs and symptoms may appear abruptly with bleeding or fever, or
they may be insidious with progressive weakness, fatigue, bone
and/or joint pain, and bleeding tendencies
• Central nervous system (CNS) manifestations are especially common
in ALL and are a serious problem.
• Infiltration into other tissues and lymph nodes can occur.

28. Chronic Myelogenous Leukemia
• CML is caused by excessive development of neoplastic granulocytes in
the bone marrow.
• These granulocytes are in all stages of development.
• They move into the peripheral blood in massive numbers and
infiltrate the liver and spleen.
• The natural history of CML is a chronic stable phase followed by the
development of a more acute, aggressive phase referred to as the
blastic phase.

29. Chronic Lymphocytic Leukemia
• CLL is the most common leukemia in adults in Western countries.
• CLL is characterized by the production and accumulation of
functionally inactive but long-lived, small, mature-appearing
lymphocytes.
• B cells are usually involved. The lymphocytes infiltrate the bone
marrow, spleen, and liver.
• Lymph node enlargement (lymphadenopathy) is present throughout
the body.

30. Pathophysiology

31. Clinical features
Acute myelogenous leukemia
Fatigue, weakness, headache, mouth sores,
anemia, bleeding , fever, infection, sternal
tenderness, hepatosplenomegaly,
lymphedenopathy
Acute lymphocytic leukemia
Fever, pallor, bleeding, anorexia, joint pain,
abdominal pain, infection, weight loss, CNS
involvement
Chronic myelogenous leukemia
Fatigue weakness, fever, sternal tenderness,
weight loss, joint pain, bone pain, splenomegaly
Chronic lymphocytic leukemia
Fatigue, anorexia, splenomegaly and
lymphadenopathy, night sweats, weight loss

32. Continued..
• Abnormal WBCs continue to accumulate as they do not go through
apoptosis.
• The leukemic cells may infiltrate the patient’s organs, leading to
problems such as splenomegaly, hepatomegaly, lymphadenopathy,
bone pain, meningeal irritation, and oral lesions
• Chloromas : Solid masses resulting from collections of leukemic cells
• Leukostasis: high leukemic white count in the peripheral blood (more
than 100,000 cells/ µL) can cause the blood to thicken and potentially
block circulatory pathways.

33. Diagnostic evaluation
1. Peripheral blood evaluation :
2. Bone marrow examination:
• Morphologic, histochemical, immunologic, and cytogenetic methods
are used to identify leukemic cell types, stage of development, and
significant genetic mutations
• CML, the finding of the Philadelphia chromosome is an important
diagnostic indicator.
3. Other studies, such as lumbar puncture and PET/CT scans:
• detect leukemic cells outside of the blood and bone marrow.

34. Diagnostic evaluation
Acute myelogenous leukemia
RBC,Hb, HCT, platelet decreases
Low to high WBC,
High LDH
Hypercellular Bone marrow
Acute lymphocytic leukemia
RBC, Hb, platelets decrease
High LDH
Hypercellular bone marrow
Lymphoblast in CSF
Philadelphia chromosome +
Chronic myelogenous leukemia
RBC, Hb, Hct, decreases
Platelet count increases in early phase, decreases in
late
Increased neutrophils, Philadelphia chromosome +
In more than 90% cases
Chronic lymphocytic leukemia
Mild anemia, thrombocytopenia,
Peripheral lymphocytes increases
Presence of lymphocytes in bone marrow

35. Management
• Chemotherapy
• Radiation and biologic therapies also may be used.

36. Stages of Chemotherapy
Chemotherapy is often divided into 3 stages:
 Induction
Post induction or post remission (consolidation)
Maintenance.

37. Induction Therapy
• The first stage, induction therapy, is the attempt to bring about a
remission.
• Purpose: Aggressive treatment that seeks to destroy leukemic cells in
the tissues, peripheral blood, and bone marrow to eventually restore
normal hematopoiesis on bone marrow recovery
• Chemotherapy agents for induction of AML : Cytarabine and an
antitumor antibiotic (anthracycline), such as daunorubicin, idarubicin,
or mitoxantrone.
• Nursing care: focus on neutropenia, thrombocytopenia, and anemia

38. Post induction therapy
• Intensification therapy: may be given immediately after induction
therapy for several months.
• Other drugs that target the cell in a different way than those given
during induction may be added.
• Consolidation therapy: Started after a remission is achieved.
• It may consist of 1 or 2 more courses of the same drugs given during
induction or involve high-dose therapy (intensive consolidation).
• Purpose of consolidation therapy: to eliminate remaining leukemic
cells that may not be clinically or pathologically evident.

39. Maintenance Therapy
• Maintenance therapy: Involves treatment with lower doses of the
same drugs used in induction or other drugs given every few weeks
for a prolonged period.
• Purpose:To keep the body free of leukemic cells.
• This is often used with ALL and extends for several years.

40. Drugs used in leukemia
Class Drug
Alkylating agent Busulfan Chlorambucil
Antitumour antibiotics (anthracyclines) Daunorubicin Doxorubicin
Antimetabolites Cytarabine Methotrexate
Corticosteroids Prednisolone Dexamethasone
Nitrosoureas Carmustine
Mitotic inhibitors/ vinca alkaloids Vincristine Vinblastin
Biologic/ Targeted therapy Rituximab

41. Radiation therapy
• Total body radiation may be used to prepare a patient for bone
marrow transplantation.
• Radiation may be restricted to certain areas (fields,) such as the liver
and spleen, or other organs affected by infiltrates
• When CNS leukemia does occur, cranial radiation is an option

42. Immunotherapy and targeted therapy
use of chimeric antigen receptor T cells,
where patient T cell are engineered to
target the malignant cells (insert).

43. Targeted therapy or precision medicine
• Purpose: Eradicating leukemic cells with specific
molecular aberrations without hitting nonspecific targets,
such as normal hematopoietic cells.
• Tyrosine kinase inhibitors: Cetuximab
• Monoclonal antibodies: Rituximab
• Angiogenesis inhibitor : Bevacizumab
• Proteosome inhibitors : Bortezomib

44. Hematopoietic Stem Cell Transplantation
• HSCT is another type of therapy used for patients with different forms
of leukemia.
• The goal of HSCT is to eliminate all leukemic cells from the body using
combinations of chemotherapy with or without total body irradiation.
• This treatment eradicates the patient’s hematopoietic stem cells,
which are then replaced with those of an HLA-matched sibling, HLA-
half-matched relative, volunteer donor (allogeneic), or identical twin
(syngeneic