Leukemias are cancers of the blood-forming tissues.

White blood cells may be produced in excessive amounts and are unable to work properly which weakens the immune system. The blood is made up of fluid called plasma and three types of cells and each type has special functions. White blood cells (also called WBCs or

leukocytes) help the body fight infections and other diseases. Red blood cells (also called RBCs or erythrocytes) carry oxygen from the lungs to the bodys tissues and take carbon dioxide from the tissues back to the lungs. The red blood cells give blood its color. Platelets (also called thrombocytes) help form blood clots that control bleeding. Blood cells are formed in the bone marrow, the soft, spongy center of bones. New (immature) blood cells are called blasts. Some blasts stay in the marrow to mature. Some travel to other parts of the body to mature. Normally, blood cells are produced in an orderly, controlled way, as the body needs them. This process helps keep us healthy. When leukemia develops, the body produces large numbers of abnormal blood cells. In most types of leukemia, the abnormal cells are white blood cells. The leukemia cells usually look different from normal blood cells, and they do not function properly. In both men and women, leukemia incidence is highest among whites and lowest among Chinese, Japanese, and Koreans. The incidence in men is about 50% higher than in women for all racial/ethnic groups except Vietnamese, among whom the male rates are only slightly higher. Ethnic differences in the incidence rates are small in the youngest adult age group (30-54 years), but become more evident in each of the older age groups. It is found that childhood leukemia rates are highest among Filipinos, followed by white Hispanics, nonHispanic whites and blacks. Anatomy and physiology Blood Blood is one of the connective tissues. As a connective tissue, it consists of cells and cell fragments (formed elements) suspended in an intercellular matrix (plasma). Blood is the only

liquid tissue in the body that measures about 5 liters in the adult human and accounts for 8 percent of the body weight. The body consists of metabolically active cells that need a continuous supply of nutrients and oxygen. Metabolic waste products need to be removed from the cells to maintain a stable cellular environment. Blood is the primary transport medium that is responsible for meeting these cellular demands. Blood cells are formed in the bone marrow, the soft, spongy center of bones. New (immature) blood cells are called blasts. Some blasts stay in the marrow to mature. Some travel to other parts of the body to mature. The activities of the blood may be categorized as transportation, regulation, and protection. These functional categories overlap and interact as the blood carries out its role in providing suitable conditions for celluar functions. The transport functions include: carrying oxygen and nutrients to the cells. transporting carbon dioxide and nitrogenous wastes from the tissues to the lungs and kidneys where these wastes can be removed from the body. Carrying hormones from the endocrine glands to the target tissues. Helping regulate body temperature by removing heat from active areas, such as skeletal muscles, and transporting it to other regions or to the skin where it can be dissipated. Playing a significant role in fluid and electrolyte balance because the salts and plasma proteins contribute to the osmotic pressure. Functioning in pH regulation through the action of buffers in the blood. Preventing fluid loss through hemorrhage when blood vessels are damaged due to its clotting mechanisms. Helping (phagocytic white-blood cells) to protect the body against microorganisms that cause disease by engulfing and destroying the agent. Protecting (antibodies in the plasma) protect against disease by their reactions with offending agents.

The regulation functions include:

The protection functions include:

Composition of blood When a sample of blood is spun in a centrifuge, the cells and cell fragments are separated from the liquid intercellular matrix. Because

the formed elements are heavier than the liquid matrix, they are packed in the bottom of the tube by the centrifugal force. The light yellow colored liquid on the top is the plasma, which accounts for about 55 percent of the blood volume and red blood cells is called the hematocrit,or packed cell volume (PCV). The white blood cells and platelets form a thin white layer, called the red blood cells.

buffy coat, between plasma and Plasma

The watery fluid portion of blood (90 percent water) in which the corpuscular elements are suspended. It transports nutrients as well as wastes throughout the body. Various compounds, including proteins, electrolytes, carbohydrates, minerals, and fats, are dissolved in it. Formed Elements The formed elements are cells and cell fragments suspended in the plasma. The three classes of formed elements are the red blood cells), thrombocytes (platelets). leukocytes ( erythrocytes ( white blood cells), and the

Erythrocytes (red blood cells) Erythrocytes, or red blood cells, are the most numerous of

the formed elements. Erythrocytes are tiny biconcave disks, thin in the middle and thicker around the periphery. The shape provides a combination of flexibility for moving through tiny capillaries with a maximum surface area for the diffusion of gases. The primary function of oxygen and, to a lesser extent, carbon dioxide. Leukocytes (white blood cells) Leukocytes or white blood cells are generally larger than erythrocytes is to transport

erythrocytes, but they are fewer in number. Even though they are considered to be blood cells, leukocytes do most of their work in the

tissues. They use the blood as a transport medium. Some are phagocytic, others produce antibodies, some secrete histamine and, heparin, and

others neutralize histamine. Leukocytes are able to move through the capillary walls into the tissue spaces, a process called diapedesis.In the tissue spaces they provide a defense against organisms that cause disease and either promote or inhibit inflammatory responses. There are two main groups of leukocytes in the blood. The cells that develop granules in the cytoplasm are called granulocytes and those that do not have granules are called agranulocytes. Neutrophils, eosinophils, and basophils are granulocytes. Monocytes and lymphocytes are agranulocytes. Neutrophils, the most numerous leukocytes, are phagocytic and have light-colored granules. Eosinophils have granules and help counteract the effects of histamine. Basophils secrete histomine and heparin and have blue granules. In the tissues, they are called mastcells. Lymphocytes are agranulocytes that have a special role in immune processes. Some attack bacteria directly; others produce antibodies. Thrombocytes (platelets) Thrombocytes, or platelets, are not complete cells, but are small fragments of very large cells called megakaryocytes. Megakaryocytes develop from hemocytoblasts in the red bone marrow. Thrombocytes become sticky and clump together to form platelet plugs that close breaks and tears in blood vessels. They also initiate the formation of Blood Cell Lineage: The production of formed elements, or blood cells, is called hemopoiesis. Before birth, hemopoiesis occurs primarily in the liver and spleen, but some cells develop in the thymus, lymph nodes, and red bone marrow. After birth, most production is limited to red bone blood clots.

marrow in specific regions, but some white blood cells are produced in lymphoid tissue. All types of formed elements develop from a single cell type stem cell (pleuripotential cells or hemocytoblasts). Seven different cell lines, each controlled by a specific growth factor, develop from the hemocytoblast. When a stem cell divides, one of the daughters remains a stem cell and the other becomes a precursor cell, either a lymphoid cell or a myeloid cell. These cells continue to mature into various blood cells.

A leukemia can develop at any point in cell differentiation. The illustration below shows the development of the formed elements of the blood. Blood-related cancers, or leukemias, have been shown to arise from a rare subset of cells that escape normal regulation and drive the formation and growth of the tumor. The finding that these so-called cancer stem cells, or leukemic stem cells (LSC), can be purified away from the other cells in the tumor allows their precise analysis to identify candidate molecules and regulatory pathways that play a role in progression, maintenance, and spreading of leukemias. The analyses of the other, numerically dominant, cells in the tumor, while also interesting, do not directly interrogate these key properties of malignancies. Mouse models of human myeloproliferative disorder and acute myelogenous leukemia have highlighted the remarkable conservation of disease mechanisms between both species. They can now be used to identify the LSC for each type of human leukemia and understand how they escape normal regulation and become malignant. Given the clinical importance of LSC identification, the insights gained through these approaches will quickly translate into clinical applications and lead to improved treatments for human leukemias. Predisposing factors The exact cause of leukemia is unknown, although many genetic and environmental factors are involved in its development. The basic mechanism involves damage to genes controlling cell growth. This damage then changes cells from a normal to a malignant (cancer) state. Analysis of bone marrow of a client with acute leukemias shows abnormal chromosomes about 50% of the time. Possible risk factors for the development of leukemia include ionizing radiation, exposure to chemicals and drugs, bone marrow hypoplasia (reduced production of blood cells), genetic factors, immunologic factors, environmental factors, and the interaction of theses factors. Ionizing radiation exposures such as radiation therapy for cancer treatment or environmental irradiation increase the risk for leukemia development, particularly acute myelogenous leukemia (AML). Certain chemicals and drugs have been linked to the development of leukemia because of their ability to damage DNA. Previous treatment for cancer that included melphaplan, cyclosphamide, doxorubicin, and etoposide poses risks for leukemia development about 5 to 8 years after treatment. Bone marrow hypoplasia can increase leukemia risk by reducing or changing bone marrow cell production. Disorders that have marrow hypoplasia and may lead to leukemia development include Fanconis anemia, paroxysmal nocturnal hemoglobinuria, and myelodysplastic syndromes. Genetic factors influence leukemia development. There is an increased incidence of the disease among clients with hereditary conditions such as Down syndrome, blooms syndrome, Klinefelter syndrome, and Fanconis anemia. Identical siblings of client with leukemia have a higher rate of leukemia than does general population. Immunologic factors, especially immune deficiencies, may promote the development of leukemia. Leukemia among immunodeficient people may be a result of immune surveilance failure, or the same mechanisms that cause the immune deficiency may also trigger cancer in the white blood cells population.

Interaction of many host and environmental factors may result in leukemia. Because each person tolerates the interaction of these factors differently, it is difficult to determine the origin of any specific leukemia. Pathophysiology Leukemia is a type of cancer with uncontrolled production of immature white blood cells (usually blast cells) in the bone marrow. As a result, the bone marrow becomes overcrowded with immature, nonfunctional calls and production of normal blood cell is greatly decreased. Leukemia may be acute, with sudden onset ans short duration, or chronic with a slow onset and symptoms that persist for a period of years. Leukemias are classified by cell type. Abnormal leukemic cells coming from lymphoid pathways are lymphocytic or lymphoblastic. Leukemias in which the abnormal cells come from the myeloid pathways are myelocytic or lymphoblastic. Several subtype exist for each of these diseases, which are classified according to the degree of maturity of the abnormal cell and the specific cell type involved. With leukemia, cancer occurs in the stem cells or early precursor leukocyte cell, causing excessive growth of a specific type of leukocyte. These cells are abnormal and their excessive production in the bone marrow stops normal bone marrow production of red blood cells, platelets, and mature leukocytes. Anemia, thrombocytopenia, and leukopenia result. The number of immature, abnormal white blood cells in the blood is greatly elevated. Leukemic cells can also be found in the spleen, liver, liver nodes and central nervous system. Without treatment, the client dies of infection or hemorrhage. For clients with acute leukemia, theae changes occur rapidly and, without intervention, progress to death. Chronic leukemia may be present for years before changes appear. Physical Manifestations Leukemias affects all blood cells, and blood influences the health and function of all organs and systems, thus many body areas and system cells may be affected. The following manifestations occur with the acute luekemias. Some of this findings may also be present in the client with chronic leukemia in the blast phase. Integumantary Manifestations: Ecchymoses Petechiae Open infected lesions Pallor of the conjunctiva, nail beds, palmar creases, and around the mouth. Bleeding gums Anorexia

Gastrointestinal Manifestations:

Weight loss Enlarged liver and spleen Hematuria Tachycardia at basal activity levels. Orthostatic hypotension Palpitations Dyspnea on exertion. Fatigue Headache Fever Bone pain Joint swelling and pain.

Renal Manifestations: Cardiovascular Manifestations:

Respiratory Manifestations: Neurologic Manifestations:

Musculoskeletal Manifestations:

Diagnostic Evaluation 1. CBC and blood smear peripheral WBC count varies widely from 1,000 to 100,000/mm3 and may include significant numbers of abnormal immature (blast) cells, anemia may be profound; platelet count may be abnormal and coagulopathies may exist. 2. Bone marrow aspiration and biopsy cells also studied for chromosomal abnormalities (cytogenetics) and immunologic markers to classify type of leukemia further. 3. Lymph node biopsy to detect the spread. 4. Lumbar puncture and examination of cerebrospinal fluid for leukemic cells (especially ALL). Treatment To eradicate leukemic cells and allow restoration of normal hematopoiesis. 1. High-dose chemotherapy given as an induction course to obtain a remission (disappearance of abnormal cells in bone marrow and blood) and then in cycles as consolidation or maintenance therapy to prevent recurrence of disease. 2. Leukapheresis (or exchange transfusion to infants) may be used when abnormally high numbers of white cells are present to reduce the risk of leukostasis and tumor burden before chemotherapy. 3. Radiation particularly of central nervous system (CNS) in ALL. 4. Autologous or allogeneic bone marrow or stem cell transplantation.

Complications 1. Leukostasis; in setting of high numbers (greater than 50,000/mm3) of circulating leukemic cells (blasts), blood vessel walls are infiltrated and weakened, with high risk of rupture and bleeding, including intracranial hemorrhage. 2. Disseminated intravascular coagulation(DIC). 3. Tumor lysis syndrome: rapid destruction of large numbers of malignant cells leads to alteration in electrolytes (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia). 4. May lead to renal failure and other complications. 5. Infection, bleeding, and organ damage. Pharmacologic Interventions Acute leukemia Different types of leukemia are best treated with different kinds of medicine. Acute lymphoblastic leukemia (ALL) drugs include prednisone, vincristine, daunorubicin, L-asparaginase or pegaspargase, methotrexate, and cyclophosphamide. Imatinib (Gleevec) is sometimes used to treat ALL. Dasatinib (Sprycel) is a newer drug for treating some ALL that has not improved with other drugs. Acute myelogenous leukemia (AML) drugs include daunorubicin, idarubicin, cytosine arabinoside, and mitoxantrone.10 Gemtuzumab (Mylotarg) may be given to people whose AML has relapsed. It helps your body destroy cancer cells. Acute promyelocytic leukemia (APL) drugs include all-trans-retinoic acid (ATRA) and chemotherapy with arsenic trioxide, idarubicin, or daunorubicin. ATRA helps control the risk of life-threatening bleeding from disseminated intravascular coagulation (DIC). Later treatment can include ATRA with or without methotrexate and 6-mercaptopurine. Or if a first round of ATRA and chemotherapy does not work, arsenic trioxide may be used.10 To treat leukemia in the brain or prevent it from spreading to the brain and central nervous system, methotrexate and cytarabine/cytosine arabinoside are injected into the spinal canal. This is called intrathecal chemotherapy.

Supportive treatments during cancer treatment include: Antibiotics and immunoglobulins help to prevent or fight infections. This is important when you do not have enough normal white blood cells to fight infections on your own. Transfusions of red blood cells and platelets. Epoetin and hematopoietic stimulants help your body make new blood cells. Allopurinol to prevent kidney problems and gout. Saline or steroid eyedrops for relief during treatment with cytarabine/cytosine arabinoside.

Chronic leukemia Chemotherapy for chronic leukemia can involve a single drug or a combination of drugs. For example, you may be given a combination of cyclophosphamide, vincristine, and prednisone. Other drug choices include fludarabine, chlorambucil, hydroxyurea (hydroxycarbamide), cytarabine, busulfan, rituximab, and alemtuzumab. Allopurinol may be given to prevent kidney problems and gout. Dasatinib (Sprycel) blocks the growth of cancer cells. It can be used for CML that has not been helped by imatinib or other drugs. Imatinib (Gleevec) blocks the growth of cancer cells. It is often given to people who have chronic myelogenous leukemia (CML). Immune globulin (IG) helps prevent infections. It is sometimes used for people with chronic lymphocytic leukemia (CLL), because CLL weakens the immune system. Interferon alfa helps your immune system fight disease and may keep cancer cells from growing. It is often given to people who have CML.

Medication for nausea and vomiting Nausea and vomiting are common side effects of chemotherapy. These side effects usually are temporary and go away when treatment is stopped. Your doctor will prescribe drugs to help relieve nausea. These may include: Aprepitant (Emend), which is used in combination with ondansetron and dexamethasone as part of a 3-day program. Dimenhydrinate, such as Dramamine. Metoclopramide, such as Reglan and Octamide. Phenothiazines, such as Compazine and Phenergan. Serotonin antagonists, such as ondansetron (Zofran), granisetron (Kytril), or dolasetron (Anzemet). These drugs work best when they are combined with corticosteroids such as dexamethasone (Hexadrol).

Nursing Interventions Preventing infection: Frequently monitor the client for pneumonia, pharyngitis, esophagitis, perianal cellulitis, urinary tract infection, and cellulitis, which are common in leukemia and which carry significant morbidity and mortality. Monitor for fever, flushed appearance, chills, tachycardia; appearance of white patches in the mouth; redness, swelling, heat or pain in the eyes, ears, throat, skin, joints, abdomen, rectal and perineal areas; cough, changes in sputum; skin rash. Check results of granulocyte counts. Concentrations less than 500/mm3 put the patient at serious risk for infection. Avoid invasive procedures and trauma to skin or mucous membrane to prevent entry of microorganisms.

Use the following rectal precautions to prevent infections: Avoid diarrhea and constipation, which can irritate the rectal mucosa, avoid the use of rectal thermometers, and keep perineal are clean. Care for the patient in private room with strict handwashing practice. Encourage and assist patient with personal hygiene, bathing, and oral care. Obtain cultures and administer antimicrobials promptly as directed. Watch for signs of minor bleeding, such as petechiae, ecchymosis, conjunctival hemorrhage, epistaxis, bleeding gums, bleeding at puncture sites, vaginal spotting, heavy menses. Be alert for signs of serious bleeding, such as headache with change in responsiveness, blurred vision, hemoptysis, hematemesis, melena, hypotension, tachycardia, dizziness. Test all urine, stool, emesis for gross and occult blood. Monitor platelet counts daily. Administer blood components as directed. Keep patient on bed rest during bleeding episodes. Teach signs and symptoms of infection and advise whom to notify. Encourage adequate nutrition to prevent emaciation from chemotherapy. Teach avoidance of constipation with increased fluid and fiber, and good perineal care. Teach bleeding precautions. Encourage regular dental visits to detect and treat dental infections and disease.

Preventing and Managing bleeding:

Patient Education and Health Maintenance: