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Leukemia Leukemia

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Leukemia - PPT Presentation

Rita All Carrie Warner Definition Leukemia is a group of malignant diseases that result in changes to circulating lymphocytes characterized by diffuse abnormal growth of leukocytic precursors in the marrow ID: 330909

cancer leukemia 2013 cells leukemia cancer cells 2013 treatment 2014 marrow blood chronic lymphoma years bone cml burns due high acute cases

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Slide1

Leukemia

Rita All

Carrie WarnerSlide2

Definition

Leukemia is a group of malignant diseases that result in changes to circulating lymphocytes characterized by diffuse, abnormal growth of

leukocytic

precursors in the marrow.

The uncontrolled increase in immature white blood cells suppresses normal hematopoietic stem cells leading to anemia and thrombocytopenia.

Causes life threatening infections due to ineffective WBC function.

Classification is made by the course of the illness and types of cells and tissues involved.

Staging is not possible as it is already circulating.

(Burns, 2013; Larson, 2014).Slide3

Normal blood versus leukemia blood

(American Cancer Society, 2014)Slide4

Leukemia Vs. Lymphoma

According to the American Joint Committee on Cancer (AJCC)

Circulating cells= leukemia

Tumor masses in lymph nodes and tissues= lymphoma

If both= lymphoma/leukemia

Emerging research suggests these are the same diseases in different stages

Chronic lymphocytic leukemia= small lymphocytic lymphoma (a form of non-

Hodgkins

lymphoma)

If greater than 25% of marrow replaced by cancerous lymphocytes, it is usually considered leukemia.

Also if the lymph nodes are very large, diagnosis will generally be lymphoma.

(American Cancer Society, 2014)Slide5

Pathophysiology

Normal bone marrow elements are replaced with blast cells that are abnormal and poorly differentiated.

The abnormal cells (

Lymphoblasts

or Myeloid cells) take over and cause unregulated

clonal

proliferation of malignant cells, crowding out other healthy cell groups.

Chronic lymphocytic leukemia progresses slowly and can last decades.

People with Chronic Myeloid leukemia acquired a chromosomal abnormality that causes part of one chromosome to break off and join another, the short chromosome called the Philadelphia chromosome, which produces an enzyme that causes WBCs to grow out of control, that can ultimately result in acute leukemia.

(Larson, 2014)Slide6

Genesis of blood cells

(National Cancer Institute, 2013)Slide7

Etiology

Unknown etiology for all types, but higher incidences with some that have:

Infection

Radiation

Chemical and Drug exposure

Epstein- Barr may play a role in in

Burkitt

leukemia/ lymphoma.

Genetic mutations may lead to disruption of lymphocytes and prolonged survival.

(Domino, 2014; Burns, 2013; National Cancer Institute, 2013). Slide8

Incidence

There were 48,610 new cases of leukemia in 2013, 2.9% of all cancer cases.

There were 23,720 deaths in 2013 from leukemia, 4.1% of all cancer deaths.

The five year survival rate for leukemia is 56%

Leukemia is the most common form of childhood cancer, 41% of pediatric malignancies in children less than 15 (Burns, 2013).

Four main types of

leukemias

, with many rare

varants

and subtypes.

ALL- In the US- 1,000 adult cases per year, median age 35-40 years old, incidence increases with age, males slightly more prevalent than females. Accounts for 80% of all childhood leukemia cases, peak age 2-6 years old. Occurs one out of every 29,000 children annually (Burns, 2013).

AML- Increases with age, median age 70 years. 13,500 cases in 2007, second most common type of leukemia for adults and children. Affects males slightly more than females.

CLL- 15,000 to 17,000 new cases reported annually. Most common form of leukemia in adults. Median age of diagnosis is 70 years, with rising incidence in those greater than 55 years old. Males have higher incidence 1.7:1, and higher with Caucasian than African Americans.

CML- 1.6 cases per 100,000 annually. Greatest in 50-60 year olds, with males having higher incidence 1.3:1. Accounts for 15-20 % of adult

leukemias

(Burns, 2013; Domino, 2014)Slide9

Leukemias

(Lee, 2009)Slide10

Screening

There is no individual screening test for

Leukemias

.

Those with risk factors can be monitored more diligently with routine exams and labs.

Routine or illness physical: Presence of

organomegaly

-

hepatosplenomegaly

, enlarged lymph nodes.

CBC with Differential (Often found during routine exam or illness)

Low or high white blood cells, varying levels of

neutropenia

Thrombocytopenia present in 85 % of cases

Peripheral smear- malignant cells

Low hemoglobin, less than 9.0

Liver Function Tests may show elevations

(Burns, 2013)Slide11

Risk Factors

ALL- Less than 15 years old, greater than 60 years old. Chemical exposure to benzene or radiation. Can follow

aplastic

anemia.

AML- Genetic predisposition (Down’s syndrome, Bloom’s syndrome),

Fanconi

anemia, neurofibromatosis, Li-

Fraumeni

Syndrome,

Wiskott

- Aldrich syndrome,

Kostmann

syndrome, and Diamond-

blackfan

anemia. Radiation exposure, Immunodeficiency states, Chemical and drug exposure (nitrogen mustard, benzene),

Myelodysplastic

syndromes, Cigarette smoking (20%).

CLL- Mostly uncertain risk factors, possible chronic immune stimulation.

CML- Ionizing radiation exposure

All

leukemias

: possibly other causes such as workplace exposures from organic solvents, pesticides, herbicides, hair dyes; electromagnetic fields, birth weight over 7.7 lbs, mom over 35 yrs at birth, and parent exposures.

(Domino, 2014).Slide12

Clinical Findings

Children:

Signs and symptoms related to leukemic replacement of bone marrow/ absence of blood cell precursors

Anemia, Pallor, listlessness

Irritability, chronically tired

History of repeated infections, fever, weight loss

Bleeding-

epistaxis

,

petechiae

, hematomas

Lymphadenopathy

and

hepatosplenomegaly

Bone and joint pain

CNS symptoms if brain involvement

Abnormal CBC, low or high white cell count with out of proportion differential

Testicular pain

(Burns, 2013)

Adults:

Acute forms have bone and joint pain

Gingival hyperplasia with bleeding

S/S infection- Fevers, chills, palpitations, shortness of breath

Skin eruptions, easy bruising, prolonged bleeding times

Chronic forms c/o fatigue, night sweats, low grade fevers

CML-

leukostasis

- blurred vision, respiratory distress,

priapism

Organomegaly

with chronic form,

hepatosplenomegaly

with enlarged spleen and lymph nodes, assoc with N/V

Pallor, Anemia

Abnormal CBC, low or high white cell count with out of proportion differential

(

Dunphy

, 2011)Slide13

Differential Diagnosis

Acute Lymphocytic Leukemia

AML

CML in Lymphoid blast phase

Prolymphocytic

leukemia

Malignant Lymphomas

Multiple Myeloma

Bone marrow metastases from solid tumors (breast, prostate, lung, renal)

Myelodysplastic

syndromes

Aplastic

anemia

Myelofibrosis

Autoimmune disease (lupus,

felty

syndrome)

Infectious mononucleosis

Pertussis

Autoimmune Thrombocytopenia

purpura

Leukemoid

reaction to infection

(Domino, 2014).

Acute Myeloid Leukemia

Virus Induced

Cytopenia

,

lymphadenopathy

, and

organomegaly

Immune

Cytopenias

(including Systemic lupus

erythmatosis

)

Drug induced

cytopenias

Other marrow failure and infiltrative disease (

aplastic

anemia, paroxysmal nocturnal

hemoglobinuria

,

myelodysplastic

syndromes,

Gaucher

disease)

(Domino, 2014).Slide14

Differential Diagnosis

Chronic

Myelogenous

Leukemia

Chronic

Myelomonocytic

leukemia

Chronic

neutrophilic

leukemia

Chronic

eosinophilic

leukemia

Juvenile

myelomonocytic

leukemia

Infectious mononucleosis

Leukemoid

reaction

Polycythemia

vera

Treatment with granulocyte stimulating factors

Acute

myelogenous

leukemia

Acute lymphoblastic leukemia

Atypical CML

(Domino, 2014).

Chronic Lymphocytic Leukemia

Bacterial Tuberculosis

Infectious mononucleosis

Non

hodgkins

Lymphoma

Hairy cell leukemia

Waldenstrom

macroglobulinemia

Large granular lymphocytic leukemia

(Domino, 2014

).Slide15

Social/ Environmental Considerations

For children:

No physical activities

Limited exposure to other children and family members due to risk of contracting infection.

Frequent hospitalizations for treatments, and follow ups.

Frequent illness due to disease and treatment modalities.

Changing of physical self, loss of hair, swelling, pale skin and dark circles under eyes, weight loss, central lines or ports.

Limited exposure to animals.

Family pressures with medical bills and transportation.

Threat of mortality.

For adults:

Frequent monitoring, hospitalizations for testing, treatments, and follow up.

Missed work, or need for leave of absence.

Loss of income due to missed work time, leave of absence, and elevated medical bills.

Family dynamic changes, the primary caregiver may become the one being cared for.

Changing of physical self, loss of hair, swelling, pale skin and dark circles under eyes, weight loss, central lines or ports.

Family pressures due to decreased income, increased bills, changes in family dynamics, and feeling of lack of self worth.

Threat of mortality.

(

Dunphy

, 2011; Larson, 2014)Slide16

Laboratory tests/ diagnostics

CBC with Manual Differential

Low or high white blood cells, varying levels of

neutropenia

Thrombocytopenia present in 85 % of cases

Peripheral smear- malignant cells

Low hemoglobin, less than 9.0

Uric acid level

Can be elevated or high

LDH

Elevated

PCR (polymerase chain reaction)

Presence of biomarkers in blood/ bone marrow cells . DNA abnormality marker with AML or CML “

philadelphia

chromosome”

Liver Function Tests

Elevation due to inflammation of liver

Sed

Rate

Elevation

CRP

Elevation

Bone marrow

Bx

/ aspiration

Replacement of normal marrow cells by blast cells

Should parallel peripheral smear

Lumbar Puncture, CXR, CT scans, MRIs- to rule out other pathology, CNS involvement,

hepatosplenomegaly

(Burns, 2013)Slide17

Management/ Treatment Guidelines

Treatment varies on

Type of leukemia

If chronic, usually asymptomatic, immediate treatment may not be required

Goal is for regular checkups, control disease and symptoms, and is seldom curable.

If acute, treatment begins right away

Goal is Remission, prevention of relapse, and it can be curable.

Extent of disease

If has been treated for cancer before

Age, symptoms, general health

Maintaining health physically and mentally

(National Cancer Institute, 2013). Slide18

Management/ Treatment Guidelines

Bone marrow transplant

Splenectomy

Radiation

Clinical trials

Nutritional support (IV fluids/

hyperalimentation

)

Avoidance of

antiplatelets

(ASA)

Neutropenic

guidelines/ reverse isolation for infection prevention

Blood transfusions

(Domino, 2014)Slide19

Treatment guidelines

ALL- 4 phases of treatment

Remission induction chemotherapy

One month

Kill as many cancer causing cells as possible

Corticosteroids

Transfusions

goal- Induce remission

Consolidation, or CNS prophylaxis

Preventative therapy

Stops spread to brain/ spinal cord

High Dose IV or

Intrathecal

chemo

Radiation to the brain PRN

Usually lasts 2-6 months

Intensification therapy

Starts when in remission

high dose chemo to kill any lingering cells1-2 times, 1-2 months each time

Maintenance therapy

Chemo for several years to remain in remission

Girls- 2 years, Boys- 3 years

AML- Intermediate and high risk patients curative potential only from Bone marrow transplant.

Transretinoic

acid and arsenic trioxide promote maturation to granulocytes.

Idarubicin

is used for induction therapy in 3-4 cycles.

CLL- Most patients do not require active treatment.

Early treatment is not advised.

High risk patients are only treated.

Three main groups of drugs: (COP or CHOP treatment-

cyclophosphamide

,

vincristine

, prednisone, doxorubicin)

1.

Alkylating

agents-

chlorambusil

,

bendamustine

,

cyclophosphamide

2.

Purine

analogues-

fludarabine

,

pentostatin

3. Monoclonal antibodies-

rituximab

,

alemtuzumab

CML- Bone marrow transplant is the only known cure. TKI’s (

imatinib

) provide long term control of disease, no immature blood cells, and no

Philadelpha

positive metaphases.

(

Katzung

, Masters, & Trevor, 2012).Slide20

Leukemia pharmacology

Chemotherapeutics- common toxic side effects include nausea, vomiting,

immuno

and

myelosuppression

. Can also cause

hepato

,

nephro

, and neurotoxicity. They are often used in multiples.

Alkylating

agents- DNA synthesis and function inhibition, as well as mitosis inhibition and catastrophe, leading to cell death. (

bendamustine

,

Cyclophosphamide

,

Busulfan

)

Antimetabolites

- Inhibit DNA synthesis and repair (

Cytarabine

,

Fludarabine

,

Cladribine

, 6-MP, 6-

Thioguanine

,

methotrexate

)Antitumor antibiotics- oxygen free radicals bind to DNA and RNA breaking it and interfering with replication. (Daunorubicin, Idarubicin)Asparginase- enzyme isolated from E coli, hydrolyzes L asparagine, causing rapid inhibition of protein synthesis.Imatinib- Inhibits tyrosine kinase in Philadephia chromosome related CML.Corticosteriods

- used in conjunction with Chemotherapeutics to decrease inflammation,

immunosuppression

, and further chances for remission.

(

Katzung

, Masters, & Trevor, 2012).Slide21

Complications

Infection

Anemia

Excess bleeding/ bruising (low PLT)

Clotting disorders ( elevated PLT), DVT, CVA

Richter transformation- 3-5% of patients with CLL develop diffuse large B cell lymphoma, and prognosis is generally poor.

Other cancer developments due to cancer or treatments- Kaposi Sarcoma, Melanoma, Bladder, Lung, stomach, throat cancers.

Hairy cell leukemia- can develop

hodgkins

, non-

hodgkins

, thyroid ca.

Kidney failure (Rare)

Ruptured spleen (due to enlargement)

CNS involvement- seizures, headache, vomiting, confusion, loss of coordination

Depression

Pain (increased WBC in marrow)

Infertility

Death

Therapy related illness, including

avascular

necrosis, transfusion reaction, neurotoxicity, tumor

lysis

syndrome,

Late effects (66%)- learning disabilities, poor work performance, psyche distress, health insurance discrimination, “chemo brain”- inability to concentrate.

(

Dunphy

, 2011; Burns, 2013)Slide22

Follow up

Chronic

leukemias

Recommended check ups every 6 months

Acute

leukemias

Every month after treatment for the first year

To monitor for health changes and treat as necessary

Monitor for return of cancer or the worsening of chronic

Leukemias

Physical exam, blood tests, bone marrow tests, other tests as indicated.

(National Cancer Institute, 2013). Slide23

Counseling/ Education

Support groups for patient and family can be helpful with resources, education and support. Immunizations need to be up to date

ie

: flu,

pneumovac

At time of diagnosis: How to care for yourself before treatment, avoidance of infection, rest, planning.

During therapy: Managing your symptoms, sexual changes and prevention of pregnancy, preventing and treating infections, preventing clotting, bleeding, staying active, relaxation, limiting visitors without isolation, coping with stressors.

After treatment: Keeping follow up appointments, normalizing life again, monitoring for infections, “late effects”

Stop smoking!

(National Cancer Institute, 2013). Slide24

Consultation/ Referral

Hematologist

Medical Oncologist

Pediatric oncologist

Radiation oncologist

Oncology nurse

Social worker

Registered dietician

Gastroenterologist,

Nephrologist

, Neurologist as needed

Cancer Centers *

* Cancer centers are recommended for

Leukemias

, especially acute forms

Gynecologist

Complementary therapists: Acupuncture, Reiki, Meditation, Hypnosis,

Aromatherapist

Hospice

Pain management

Cancer rehabilitation

Home care

Psychiatrist, counselors

Physical therapy

Spiritual/ Religious counselors

(National Cancer Institute, 2013). Slide25

Questions

1. True or false? The goal of acute Leukemia is remission.

2. True or false? The etiology of most types of leukemia is unknown.

3. What is the median age for AML and CLL?

a.) 30

b.) 50

c.) 10

d.) 70

4. What is the most common type of leukemia in children?

a.) ALL

b.) AML

c.) CML

d.) CLLSlide26

Questions

5. A patient presents to the office with newly diagnosed Chronic lymphocytic leukemia. They want to know when their therapy will begin. You tell them:

a.) Treatment begins right away

b.) Early treatment is not recommended for those patients not at high risk

c.) Treatment begins when the patient is infection free

6. What types of leukemia would a Bone marrow transplant be the only curative measure?

a.) ALL and CLL

b.) AML and CML

c.) ALL and AML

d.) CLL and CML

7. A patient comes into the office and is concerned about the staging of their leukemia. You tell them:

a.) Blood cancers are already widespread, so there is no staging like tumor related cancers.

b.) Their cancer is staged based on their age.

c.) Their cancer is based on the amount of symptoms they are currently experiencing.Slide27

Questions

8. The difference between lymphoma and leukemia is:

a.) Leukemia occurs in the white blood cells and lymphoma occurs in the marrow

b.) Leukemia occurs in the white blood cells and lymphoma occurs in the lymph tissue

c.) The two are exactly the same.

9. A 32 year old female who has been in remission for 5 years with ALL comes to the office because she has not been able to get pregnant. You tell her:

a.) Keep trying, it will happen.

b.) She should not ever have children due to the risk of relapse.

c.) She may have infertility issues due to her treatments, and should see an OB/GYN right away.

10. A 42 year old who was recently diagnosed with AML. Which of the following would least likely be a risk factor for this type?

a.) gender

b.) smoking

c.) chemical exposure

d.) family historySlide28

References

American Cancer Society. (2014). Leukemia – Acute Lymphocytic (Adults). Retrieved from http://www.cancer.org/acs/groups/cid/documents/webcontent/003109-pdf.pdf.

Burns, C. (2013).

Pediatric Primary Care

(5

th

ed.). Philadelphia: Elsevier Health.

Domino, F. (2014).

The 5- Minute Clinical Consult

(14

th

ed.). Philadelphia: Lippincott Williams & Wilkins.

Dunphy

, L. (2011).

Primary Care: The art and science of Advanced practice nursing

. (3

rd

ed.). Philadelphia: F.A. Davis Company.

Katzung

, B., Masters, S., & Trevor, A. (2012).

Basic and Clinical Pharmacology

(12

th

ed.). New York: McGraw Hill Medical.

Larson, R. (2014). Leukemia.

UpToDate

. Retrieved from

http://www.uptodateonline.com

.

Lee, S. (2009). Pathology 2: Leukemia chart. NCNM. Retrieved from http://ncnmnotes.blogspot.com/2009/12/pathology-ii-leukemia-chart.html.National Cancer Institute. (2013). Childhood Acute Lymphoblastic Leukemia Treatment. National Institute of Health. Retrieved from http://www.cancer.gov/cancertopics/pdq/treatment/childALL/Patient/page1.