LEUKEMIARita 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.

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).

Normal blood versus leukemia blood

(American Cancer Society, 2014)

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)

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)

Genesis of blood cells

(National Cancer Institute, 2013)

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).

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)

Leukemias

(Lee, 2009)

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)

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).

Clinical FindingsChildren: 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)

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).

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).

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)

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)

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 healthMaintaining health physically and mentally(National Cancer Institute, 2013).

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)

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).

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).

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)

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).

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).

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).

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.) 30b.) 50c.) 10d.) 70

4. What is the most common type of leukemia in children?a.) ALLb.) AMLc.) CMLd.) CLL

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 awayb.) Early treatment is not recommended for those patients not at high riskc.) 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 CLLb.) AML and CMLc.) ALL and AMLd.) 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.

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 tissuec.) 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.) genderb.) smokingc.) chemical exposured.) family history

ReferencesAmerican 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 (5th ed.). Philadelphia: Elsevier Health.

Domino, F. (2014). The 5- Minute Clinical Consult (14th ed.). Philadelphia: Lippincott Williams & Wilkins.

Dunphy, L. (2011). Primary Care: The art and science of Advanced practice nursing. (3rd ed.). Philadelphia: F.A. Davis Company.

Katzung, B., Masters, S., & Trevor, A. (2012). Basic and Clinical Pharmacology (12th 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.