Leukemia Fin

7/27/2019 Leukemia Fin

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I. General Information

Leukemia is a neoplastic proliferation of one particular cell type.

Greek leukos = "white" and aima= "blood".

The defect originates in the hematopoietic stem cell, the myeloid, or the lymphoid stem cell .

Is a cancer of the blood or bone marrow. A person who has leukemia suffers from anabnormal production of blood cells, generally leukocytes (WBC).

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Types of Leukemia

1. Chronic Leukemia

a. Chronic Lymphoid Leukemia (CLL)

b. Chronic Myeloid Leukemia (CML

-About 2 to 3% of children with leukemia have CML.

-Myeloid stem cells don't mature and may not function normally. Usually, the stem cells turninto myeloblasts, but then the myeloblasts don't turn into healthy granulocytes.

-immature cells crowed out other healthy blood cells

2. Acute Leukemiaa. Acute lymphocytic (lymphoblastic) leukemia (ALL)

-Lymphocytes do not mature the way they should, so they cannot fight infection well

-too many immature lymphocytes which crowd out other types of health blood cells

-Cancer is more common in B cells than T cells.

-s/s: Low RBC (anemia) and low platelet (prone to bruising or bleeding)

b. Acute Myeloid Leukemia (AML)

-Myeloid stem cells don't mature and cannot function normally. Usually, the stem cells turninto myeloblasts, but dont turn into healthy granulocytes.

-immature cells crowed out other healthy blood cells

3. Other Types of Leukemia

a. Juvenile myelomonocytic leukemia (JMML)

-In about 1-2% of children with leukemia


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-mainly affects children 15,000 Age 55y/o and above

CML Myeloid Cells Slow Near 5,000 Mainly adults

ALL Lymphocytes Fast >5,000 Young ChildrenAML Myeloid Cells Fast >13,000 Adults and Children

Signs and Symptoms

o Feeling weak, tired or generally unwell

o Frequent Infections

o Unexplained Fevers

o Abnormal Bruising or Excessive Bleeding

o Bone and Joint Pain

o Enlarged Lymph Nodes

o Abdominal Discomfort

o Easy Shortness of Breath

II. Epidemiology


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A. International

an estimated 350,000 people are diagnosed with leukemia each year,with approximately 257,000 deaths annually.

In 2013, 48,610 people are expected to be diagnosed with leukemia.

In 2013, 23,720 people are expected to die from leukemia.

Approximately 31 % more males are living with leukemia than females.More males than females are diagnosed with leukemia and die ofleukemia.

Leukemia causes almost one-third of all cancer deaths in children andadolescents younger than 15 years

Most cases of leukemia occur in older adults; the median age atdiagnosis is 66 years.

In 2013, leukemia is expected to strike approximately 12 times as manyadults (43,749) as children and adolescents (3,605, ages 0-14 years).

Leukemia is diagnosed 10 times more often in adults than in children.

Leukemia accounts for about 33% of cancer cases in children aged 0-14

B. National

3,500 Estimated number of children diagnosed every year.

Accounts for 60%of all childhood cancers among Filipino children

80%could be potentially cured

Only 16-20%actually attain long term survival

Childhood leukemia and lymphoma relative survival was much lower in

Filipinos living in the Philippines (32.9 and 47.7%)

More than 2/3 late stages at diagnosis


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III. Risk Factors

GENERAL: WHITE MALE OVER 50: WHITE MALE OVER 50

Gender: Leukemia occurs more often in men than women.

Age: 60% to 70% of cases of leukemia are diagnosed in

patients ages 50 and over.

Race: Leukemia is more common among white people thanother races.

I. GENETICS

Family history : Most leukemia have no familial link.However, first degree relatives of CLL patients, orhaving an identical twin who has or had AML or ALL,may put you at an increased risk for developing the

disease. If an identical twin develops childhoodleukemia, the other twin has about a 1 in 5 chance ofgetting leukemia as well.

Genetic Disorders:

Li-Fraumeni syndrome : This is a rare condition caused by change in the TP53 tumor

suppressor gene. People with this change have an increased risk of developing several

C. Local

Leukemia comprises about 13 % of the cancer cases in the country andabout 65 % of leukemia patients are children, which is why the DOH has aprogram on this.

Leukemia has the most number of cases. In 2011 alone, they recorded 537leukemia consultations.

Of the recorded 537 cases in BGHMC for 2011, Dr. Igama also stressedthat it does not reflect the real number of cases they see, although she alsoaffirmed that such follow-ups and consultations in BGHMC is increasingbecause of the free medicines given under the DOH program and thecapability of the hospital in terms of experts and their capacity to handlesuch cases.

27 % cases leukemia cases in children.


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kinds of cancer, including leukemia, bone or soft tissue sarcomas, breast cancer,adrenal gland cancer, and brain tumors.

Down syndrome (trisomy 21):

Children with Down syndrome are many times more

likely to develop either acute lymphocytic leukemia(ALL) or acute myeloid leukemia (AML) than are otherchildren, with an overall risk of about 2% to 3%. Down

syndrome has also been linked with transient leukemia.

Klinefelter syndrome : This causes infertility, prevents normal development of somemale features, and is linked to a slightly increased risk of developing leukemia.

Neurofibromatosis: is a genetically-inherited disorderin which the nerve tissue

grows tumors (neurofibromas) that may be benign and may cause serious damage bycompressing nerves and other tissues. The lifetime risk of cancer developing in aperson with NF1 is estimated to be about 7%. This generally happens when a benign

(non-cancerous) neurofibroma turns into a cancerous form called sarcoma, which growsmuch faster, invades nearby structures and sometimes metastasizes (spreads) to otherregions of the body.

Fanconi anemia: is the result of a genetic defect in a cluster of proteins responsible for

DNA repair. FA patients are at elevated risk for the development of acute myeloidleukemia (AML).

Inherited immune system problems:

Ataxia Telangiectasia: Ataxia telangiectasia (A-T) (also referred to as LouisBar

syndrome) is a rare, neurodegenerative, inherited disease causing severe disability.Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, bothof which are hallmarks of the disease.

Wiskott-Aldrich syndrome: is a rare X-linked recessive disease characterized by

eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea(secondary to the thrombocytopenia).

Bloom Syndrome: is a rare autosomal recessive disorder characterized by short stature

and predisposition to the development of cancer.

II. LIFESTYLE

Smoking: Smoking is a considerable risk factor forleukemia, especially a type of leukemia called acutemyelogenous leukemia, or AML. It is estimated that 1 in 4cases of AML are caused by smoking.

Alcohol Consumption: Some studies have suggested thatif a mother drinks a lot of alcohol during pregnancy it mightincrease the risk of leukemia in her child.

*Vit B12 and Folate Deficiency: Can present as leukemia
https://en.wikipedia.org/wiki/Genetic_disorderhttps://en.wikipedia.org/wiki/Tumorshttps://en.wikipedia.org/wiki/Neurofibromahttps://en.wikipedia.org/wiki/Benign_tumorhttps://en.wikipedia.org/wiki/Genetic_disorderhttps://en.wikipedia.org/wiki/Tumorshttps://en.wikipedia.org/wiki/Neurofibromahttps://en.wikipedia.org/wiki/Benign_tumor


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TYPE OF RADIATION1. Non-ionizing radiation: Has sufficientenergy only for excitation. Weak and is unableto cause cell damage that could lead to cancer.2.Ionizing radiation: Has enough energy tobreak certain chemical bonds, remove electronsfrom atoms, and damage DNA in our cellsthat can lead to cancer

HOW RADIATION CAUSE CELL DAMAGE:1. Direct radiation action - it harms a

molecule directly; as for example whenradiation interferes with a molecule of DNA,causing cell damage.

2. Indirect damage - by ionizing molecules,turning them into potentially toxic compoundswhich interact with healthy molecules andcause damage.

III. ENVIRONMENTAL FACTORS

A. Radiation Exposure

People exposed to very high levels ofradiation are much more likely thanothers to get acute myeloid leukemia,chronic myeloid leukemia, or acutelymphocytic leukemia.

Atomic bomb explosions: Very high

levels of radiation have been causedby atomic bomb explosions (such asthose in Japan during World War II).People, especially children, whosurvive atomic bomb explosions, areat increased risk of leukemia.

Radiation therapy: Another source

of exposure to high levels of radiationis medical treatment for cancer andother conditions. Radiation therapy can increase the risk of leukemia.

Diagnostic x-rays: It's not known yet whether this low level of radiation to children or

adults is linked to leukemia. Researchers are studying whether having many x-raysmay increase the risk of leukemia.

B. Exposure to other chemicals

Benzene: Exposure to chemicals such as benzene (a solvent used in the

cleaning industry and to manufacture some drugs, plastics, and dyes) maycause AML in adults and, rarely, in children.

Radiation Doses and Expected EffectsAmount ofRadiation

DurationofExposure

Effect

0-5 rem Shortperiods orover a longperiod

No observable health effects.

5-10 rem Shortperiods orover a longperiod

Effect is either nonexistent or toosmall to observe

10-50 rem Short

periods orover a longperiod

Above 10 rem the chances of getting

cancer are slightly increased.

50-100 rem Short time Likely cause some observable healtheffectsShort-term blood cell decreases fordoses of about 50 rem

Longperiods

Increase the chances of gettingcancer

100-200rem

Short Time Nausea and Fatigue

LongPeriods

Increase a persons chances ofgetting cancer

200-300rem

Short Time Nausea and vomiting within 24-48

hours. Medical attention should besought.

300-500rem

Short Time Nausea, vomiting, and diarrhea withinhours. Loss of hair and appetiteoccurs within a week. Medicalattention must be sought for survival;half of the people exposed to radiationat this high level will die if they receiveno medical attention.

500-1200rem

Short time Lead to death in a few days

>10,000 rem Short time Lead to death in a few hours
http://www.cancer.gov/dictionary?expand=r#radiation%20therapyhttp://www.cancer.gov/dictionary?expand=x#x-rayhttp://www.cancer.gov/dictionary?expand=r#radiation%20therapyhttp://www.cancer.gov/dictionary?expand=x#x-ray


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Pesticides: Several studies have found a possible link between childhood leukemia and

household exposure to pesticides, either during pregnancy or early childhood. Somestudies have also found a possible increased risk among mothers with workplace exposureto pesticides before birth.

Phosphocol P32: Some reports have linked it to leukemia when the drug has been

prescribed without FDA approval to treat children with bleeding between the joints causedby hemophilia.

C. Chemotherapy

Children and adults treated for other cancers with certain chemotherapy drugshave a higher risk of getting a second cancer, usually AML or ALL, later in life.Examples of Chemotherapy Drugs associated to Leukemiaa. alkylating agents: cyclophosphamide (CYTOXAN) and chlorambucil (LEUKERAN)b. epipodophyllotoxins: etoposide and teniposidec. Fludarabine (FLUDARA): for CLLd. Pentostatin (NIPENT): for CLL

*Leukemias caused by chemotherapy usually develop within 5 to 10 years of treatmentand tend to be hard to treat.

IV. OTHERS

Myelodysplastic syndrome and certain other blood disorders: People with certain

blood disorders are at increased risk of acute myeloid leukemia.

Human T-cell leukemia virus type I (HTLV-I): People with HTLV-I infection are at

increased risk of a rare type of leukemia known as adult T-cell leukemia. Although theHTLV-I virus may cause this rare disease, adult T-cell leukemia and other types ofleukemia are not contagious.

Immune System Suppression: Patients getting intensive treatment to suppress their

immune function (mainly organ transplant patients) have an increased risk of certaincancers.

IV.PATHOPHYSIOLOGY

Deactivate Tumor-

Altered Gene Structure

Activate

M eloid StemL m hoid Stem
http://www.cancer.gov/dictionary?expand=m#myelodysplastic%20syndromeshttp://www.cancer.gov/dictionary?expand=h#human%20T-cell%20leukemia%20virus%20type%201http://www.cancer.gov/dictionary?expand=m#myelodysplastic%20syndromeshttp://www.cancer.gov/dictionary?expand=h#human%20T-cell%20leukemia%20virus%20type%201


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V. DIAGNOSIS

Leukemia is typically diagnosed via abnormal results on a full blood count followed byexamination of a blood film.

Usually confirmed on a bone marrow aspirate and/or trephine biopsy looking at cellmorphology and bone marrow architecture.

Additional techniques that may be used to further classify the type of leukemia include flowcytometric immunophenotyping and genetic analysis

Physical Exam and Medical History

During the physical exam, the doctor will examine the body to check general signs of health,including checking for signs of disease, such as lumps or anything else that seems unusual.Healthcare providers will also take and review a history of the patient's health habits, pastillnesses, and treatments.

Exams and Tests

Exams and tests that are used to make a leukemia diagnosis may include blood tests and abiopsy.

Blood tests: check the level of blood cells because leukemia causes:

A very high level of white blood cells Low levels of platelets Low levels of hemoglobin, which is found inside red blood cells.The lab may also check the blood for signs that leukemia has affected theliver and kidneys.

Biopsy (removal of tissue to look for cancer cells)- only sure way to know

whetherleukemia cells are in the bone marrow. The doctor removes some bone marrow from thehipbone or another large bone then examined by pathologist under a microscope.

bone marrow aspiration- use a needle to remove samples of bone marrow.

bone marrow biopsy- use of a very thick needle to remove a small piece of bone andbone marrow.

Cytogenetic -- The lab will look at the chromosomes of cells from samples of peripheral blood,

bone marrow, or lymph nodes.

Spinal tap -- The doctor will remove some of the cerebrospinalfluid (the fluid that fills the spaces in and around the brain andspinal cord). The doctor will then use a long, thin needle toremove fluid from the spinal column. The procedure takesabout 30 minutes and is performed with local anesthesia. Thepatient must lie flat for several hours afterward to keep fromgetting a headache. The lab will check the fluid for leukemiacells or other signs of problems.
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Immunophenotyping - A test in which the cells in a sample of blood or bone marrow areexamined under a microscope to determine if malignant (cancerous) lymphocytes began from theB lymphocytes or the T lymphocytes.

Fluorescent in situ hybridization (FISH) - similar to

cytogenetic testing. It uses special fluorescent dyesthat only attach to specific parts of particularchromosomes changes like translocations from blood

or bone marrow sample visible under a microscope instandard cytogenetic tests, as well as some changestoo small to be seen with usual cytogenetic testing. Itis very accurate and can usually provide results withina couple of days.

Chest x-ray -- The x-ray can reveal signs of disease in the chest.

Staging

CML phase WHO definition

Chronicstable phase

Peripheral blood blasts fewer than 10% in the blood and bone marrow

Acceleratedphase

Blasts 10-19% of white blood cells in peripheral and/or nucleated bone marrow cells ; persistentthrombocytopenia (< 100 109/L) unrelated to therapy or persistent thrombocytosis (> 1000 109/L)

unresponsive to therapy; increasing white blood cells and spleen size unresponsive to therapy;cytogenetic evidence of clonal evolution

Blast crisis Peripheral blood blasts 20% of peripheral blood white blood cells or nucleated bone marrow cells;extramedullary blast proliferation; and large foci or clusters of blasts on bone marrow biopsy

Acute Lymphoid Leukemiaa. Adult Patient

Untreated adult ALL (It is newly diagnosed, no treatment received except to relieve symptoms)-The complete blood countis abnormal.-More than 5% of the cells in the bone marrow areblasts (leukemia cells).-There are signs and symptoms of leukemia.

Adult ALL in remission (ALL has been treated)-The complete blood countis normal.-5% or fewer of the cells in the bone marrow are blasts (leukemia cells).-There are no signs orsymptomsof leukemia other than in the bone marrow.

b. ChildUntreated: No treatment given except to reduce symptoms.In Remission: Treatment has been given and amount of white blood cells in the blood and bone

marrow are normal, and no signs or symptoms of leukemia are present.Recurrent: Leukemia has returned following treatment and period of remission.Refractory: Leukemia fails to go into remission following treatment.
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VI. TREATMENT/MANAGEMENT

Treatment for leukemia can range significantly from observation (watchful waiting) to high-dosechemotherapy and stem cell transplantation. Leukemia treatment commonly involves a combinationof therapies, such as chemotherapy , immunotherapy and radiation therapy.

I. Stem Cell Transplantation (Hematopoietic Progenitor CellTransplantation)

Stem Cell immature, blood-forming cells that candevelop into any of the three main types of blood cells

- can be found in the bone marrow, circulating(peripheral) blood and umbilical cord blood.

***For patients with leukemia, a stem cell transplant can be used to infuse healthy stem cells into thebody to stimulate new bone marrow growth, suppress the disease and reduce the possibility of arelapse.

A.Types

1. Allogeneic Stem Cell Transplant - stem cells are taken from a matching donor.

*human leukocyte antigens test: comparison of the patients blood and tissue typeagainst blood samples from the donor.

a. HLA-matched relative (most often a sibling)

b. HLA-matched unrelated donor

c. HLA miss-matched family member

d. Unrelated umbilical cord blood

2. Autologous Stem Cell Transplant - stem cells are collected from the patient themselves.The stem cells are then harvested, frozen and stored, and then given back to the patient.

B. Process

1. Before Receiving Stem Cell Transplantation:

a. Conditioning regimen - involves intensive treatment to destroy as many leukemic cellsas possible.

b. Reduced-intensity conditioning (a mini-allogeneic transplant) - uses lower, less toxicdoses of chemotherapy and/or Total Body Irradiation (TBI) before the transplant

2.Transplant Proper

Stem cells (SC) given intravenously (about 1 hour)

SC enters bloodstream

Stage Risk Clinical/Morphological Features

0 Low Lymphocytosis alonenterme ate ymp ocytos s w t ymp a enopat y

II Intermediate

Lymphocytosis with lymphadenopathy

and splenomegaly or hepatomegaly

III High Lymphocytosis with anemia

IV High

Lymphocytosis with anemia and

thrombocytopenia

RAI Classification of CLL


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stem cells travel to the bone marrow

bone marrow begin to produce new blood cells (engraftment)

***The transplant restores the supply of normal cells that have been destroyed by

the intensive therapies.

3. Follow-up: blood counts should be checked on a frequent basis to monitor process.

C. Possible Side Effect: After allogeneic stem cell transplant, patient is at risk of graft-versus-host-disease (GVHD): a condition where donated cells attack the patients tissues.

II. Chemotherapy - uses anticancer drugs to destroy tumor cells in the body by impeding theirgrowth and reproduction.

***Chemotherapy for leukemia often consists of giving several drugs together in a setregimen. Because each medication destroys tumor cells in different ways, a combination ofdrugs may make the cells more vulnerable to treatment.

A. Routes of Administration

1.Orally by mouth (pill form)

2.Intravenously injection into the vein

* central venous access catheteris placed to deliver chemotherapy, give intravenous fluids and

obtain blood samples to minimize the discomfort of multiple needle pricks.

3.Intrathecally into the fluid surrounding the brain and spinal cord

highly-targeted method of delivering leukemia treatment

allows the chemotherapy to go where it can directly destroy the cancer cells

given directly into the cerebrospinal fluid to reach leukemia cells in the central nervoussystem

delivered either through a lumbar puncture, or through a special device placed under the

scalp (Ommaya Reservoir- a plastic, dome-shaped device, with a catheter attached tothe underside used to deliver chemotherapy drugs to the central nervous system [brainand spinal cord]).

help target leukemia cells that have spread to the central nervous system

B. Types of Chemotherapy

1.Chemotherapy for Acute Leukemias begins with Induction Chemotherapy followed byIntensification (consolidation) chemotherapy

a. Induction Chemotherapy - a combination of drugs is used to destroy as many leukemia

cells as possible and bring blood counts to normal

b. Intensification (consolidation) chemotherapy - used to destroy any remaining leukemiacells that cannot be seen in the blood or bone marrow

c. Maintenance chemotherapy may be received by patients with ALL;used to reduce therisk of the disease recurring after treatment

2. Chemotherapy for Chronic Leukemias common chemotherapy is given orally.


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a. Chronic Myeloid Leukemia patient may receive Gleevec (imatinib), Sprycel(dasatinib) and Tasigna (nilotinib)

b. Chronic Lymphocytic Leukemia - may receive FCR (fludarabine, cyclophosphamide andrituximab) and bendamustine

C. Chemotherapy-Related Side Effects

1. Nausea

2. Taste Changes and Mouth Sores

3. Cardiotoxicity

4. Fatigue

5. Neuropathy

6. Hair Loss

7. Sexual Dysfunction

8. Lowered Blood Cell Counts

___________________________________________________________________________

III. Immunotherapy/Targeted Drug Therapy

*Immunotherapy (biological therapy/biotherapy) - uses the bodys ownimmune system to block the growth and spread of cancer cells by preventingthe cells from dividing or directly destroying them

*Targeted drug therapy - blocks the growth and spread of leukemia cells byinterfering with specific molecules needed for growth.

-directly target leukemia cells, helping to reduce damage to healthy cells andminimize side effects

-usually in combination with chemotherapy

-commonly used for the treatment of CLL: Campath(alemtuzumab) and Rituxan (rituximab).

A. Monoclonal Antibody Therapy

-may be used alone to destroy leukemia cells, or they may be attached to

chemotherapy drugs to deliver high concentrations of the drugs directly tothe tumor cells

-Potential Side Effects: flu-like symptoms (fever, chills, headache, etc.),skin rash, nausea, diarrhea and shortness of breath.

*Monoclonal antibodies (MAbs or MoAbs) - laboratory-produced antibodies (proteins) thatlocate and bind to specific substances (antigens) on cancerous cells and eventually destroythe cells

B. Radioimmunotherapy

-combines radiation therapy and immunotherapy

-works by attaching radioactive molecules, called radioisotopes(e.g., Yttrium-90), to monoclonal antibodies to target and destroy leukemia cells.

IV. Radiation Therapy/Radiotherapy

-uses high-energy X-rays to destroy leukemia cells, to prevent the cells from spreadingand/or to relieve symptoms


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-The area treated with radiation therapy and the dose given is based on specific leukemiadiagnosis, including the type of leukemia and symptoms. (i.e. radiation therapy may be used torelieve pain or discomfort caused by an enlarged liver or spleen, or swollen lymph nodes. It canalso help to treat pain from bone damage caused by leukemia cells growing in the bone marrow)

Common Types

1. External Beam Radiation Therapy (EBRT)

uses a machine to direct high-energy rays from outside the body ontocancerous tissues within the body

common option for chronic lymphocytic leukemia (CLL), and can help toreduce swelling in the lymph nodes, liver or spleen

Process:

i. Diagnostic and imaging tools will be used to pinpoint the treatmentarea(s) and determine the correct radiation angles and dosage.

ii. Linear accelerator(a special X-ray) will deliver high-energy rays

Advantages:

Its a fast, painless outpatient procedure.

Unlike chemotherapy, which circulates through the body, ERBT is targetedto a specific area. EBRT can deliver radiation from any angle, and shaperadiation beams to the contour of the tumor.

EBRT helps to minimize damage to healthy tissues and reduce sideeffects.

2.Total Body Irradiation (TBI)

-advanced radiation therapy that can be used to destroy cancerous cells anywhere in the body

-often serves as part of the preparation process for leukemia patients who will undergochemotherapy and stem cell transplantation.

-linear accelerator: delivers radiation therapy to the entire body

Advantages:

-When used before a stem cell transplant, TBI helps to reduce the likelihood that the body willreject the transplant.

-Total body irradiation treatments are painless and treatment time is relatively short.

-The lungs are shielded to lower the risk of damage from the radiation.

-Potential Side Effects: nausea, diarrhea, fatigue, mouth sores, and skin changes

VII. Nursing Considerations

1. Institute measures to prevent exposure to known or potential sources of infection:a. Maintain protective isolation in accordance with institutional policy (placing in a private

room)b. Maintain meticulous hand washing (staff, family and client). Post a sign over the

washbasin in the room as a reminder.c. Restrict visitors with colds, flu or infections.d. Provide good perianal hygiene twice daily and after each bowel movement.e. Restrict fresh flowers and plants.f. Restrict fresh fruits and vegetables.


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