ACUTE LYMPHOCYTIC LEUKEMIA DEFINITION: is a form of leukemia, or cancer of the white blood cells characterized by excesslymphoblasts.

Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (infiltrating) to other organs. ALL is most common in childhood with a peak incidence at 25 years of age, and another peak in old age. The overall cure rate in children is about 80%, [1] and about 45%-60% of adults have long-term disease-free survival. Acute refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of chronic lymphocytic leukemia, which has a potential time course of many years. It is interchangeably referred to as Lymphocytic or Lymphoblastic. This refers to the cells that are involved, which if they were normal would be referred to aslymphocytes but are seen in this disease in a relatively immature (also termed 'blast') state.

PATHOPYSIOLOGY:

In general, cancer is caused by damage to DNA that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth or by interrupting chemical signals that control growth. Damage can be caused through the formation of fusion genes, as well as the dysregulation of a proto-oncogene via juxtaposition of it to the promoter of another gene, e.g. the T-cell receptor gene. This damage may be caused by environmental factors such as chemicals, drugs or radiation. ALL is associated with exposure to radiation and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl nuclear reactor and atom bombs in Hiroshima and Nagasaki. In animals, exposure to benzene and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Some evidence suggests that secondary leukemia can develop in individuals treated for other cancers with radiation and chemotherapy as a result of that treatment.

INCIDENCE ALL in Children. ALL is the most common type of cancer diagnosed in children. ALL accounts for about 75% of cases of childhood leukemia. Each year, about 3,600 American children and adolescents are diagnosed with ALL. ALL can strike children of all ages, but is most likely to occur when children are 2 - 4 years of age. It is slightly more common in boys than in girls. ALL in Adults. ALL is the least common type of leukemia among adults. About 1 in 3 cases of ALL occur in adults. The survival rate has improved from zero four decades ago, to 20-75 percent currently, largely due to clinical trials on new chemotherapeutic agents and improvements in stem cell transplantation (SCT) technology. Five-year survival rates evaluate older, not current, treatments. New drugs, and matching treatment to the genetic characteristics of the blast cells, may improve those rates. The prognosis for ALL differs between individuals depending on a variety of factors: Gender: females tend to fare better than males. Ethnicity: Caucasians are more likely to develop acute leukemia than AfricanAmericans, Asians or Hispanics. However, they also tend to have a better prognosis than nonCaucasians. Age at diagnosis: children between 110 years of age are most likely to develop ALL and to be cured of it. Cases in older patients are more likely to result from chromosomal abnormalities (e.g., the Philadelphia chromosome) that make treatment more difficult and prognoses poorer. White blood cell count at diagnosis of less than 50,000/l Cancer spread into the Central nervous system (brain or spinal cord) has worse outcomes. Morphological, immunological, and genetic subtypes Patient's response to initial treatment Genetic disorders such as Down's Syndrome

TYPES: Immunophenotypes B-lymphocytic lineage subtypes These cases are identified by finding cellsurface markers on the leukemic blast cells that are identical to those thatdevelop on normal B lymphocytes. Almost 90 percent of cases are of theprecursor B or B-cell subtype. T-lymphocyticandNaturalKiller(NK)celllineagesubtypes These cases areidentified by finding cell surface markers on the leukemic blast cells that areidentical to those that develop in normal T lymphocytes. About 10 percent of casesareoftheT-andNK-cellsubtypes.

Chromosome Abnormalities

njury to chromosomes can be assessed by cytogenetics. The specific alterationin chromosomes aids in subclassifying acute lymphocytic leukemia. Forexample, a change in chromosome number 22, referred to as the Philadelphia orPh chromosome, which occurs in a small percentage of children and a largerpercentage of adults with acute lymphocytic leukemia, places the patient in ahigher risk category. The approach to therapy would be intensified in thosesubsets of patients. COMPLICATIONS: Liver and kidney damage Immediate and short-term risks of radiation therapy may include seizures, stroke, and paralysis Very high levels of uric acid in the blood, which can damage the kidneys Very high levels of calcium in the blood Abnormal blood clotting Allergic reaction Low blood sugar (hypoglycemia) -- a rare complication in young, thin children who are taking purine analogues such as mercaptopurine and thioguanine Suppression of adrenal glands in children who take short-term, high-dose corticosteroids such as prednisolone

Long-Term Complications. Fatigue is very common after chemotherapy and can be significant and long-lasting. Combinations of intrathecal chemotherapy plus brain radiation in children can cause some serious complications, including seizures and problems in learning and concentration. Methotrexate is particularly toxic. Seizures can often be treated successfully with anti-epilepsy medications. Delayed puberty. The effects of treatment in the brain can affect regions that regulate reproductive hormones, which may affect fertility later on. Chemotherapy, cranial radiation, or both can impair fertility in male and female patients. Cranial radiation can also result in impaired growth. Bone loss can occur after chemotherapy, particularly with corticosteroids and after bone marrow transplantation. Drugs are available, particularly bisphosphonates, which may help reduce this risk. Pancreatic beta-cell damage and impaired insulin response. Chemotherapy-induced beta cell damage may persist after therapy has been stopped. Heart damage. Some of the treatments increase risk factors for future heart disease, including unhealthy cholesterol levels and high blood pressure. Anthracyclines (doxorubicin, daunorubicin, epirubicin) have been associated with later development of heart failure. Lower doses used for many ALL children may not pose a high risk to the heart. Patients treated for ALL should be regularly monitored for heart risks. Stroke. Survivors of childhood leukemia are at increased risk of later stroke, especially if they received treatment with cranial radiation. Obesity. Children treated for ALL are at higher risk for obesity, possibly because the treatments trigger an earlier than normal occurrence in childhood weight gain. Corticosteroid drugs used in treatments also increase appetite, which contributes to the problem. Central nervous system. Radiation and intrathecal MTX therapy may be associated with an increased risk of mood disturbances (such as depression) among adult survivors of childhood ALL. Cranial radiation and drugs used in chemotherapy, especially specific corticosteroids and spinal injection treatments, may also impair mental functioning and cause neurologic problems, such as movement problems.

Secondary Cancers. Studies indicate that survivors of childhood ALL are at increased risk of later developing other types of cancers, including brain and spinal cord tumors, basal cell skin carcinoma, and myeloid (bone marrow) malignancies. Radiation and older types of chemotherapy are mainly responsible for this risk. Newer types of ALL treatment may be less likely to cause secondary cancers.

ASSESSMENT: Any fever of 101F or higher Any signs of a flu or cold Shortness of breath Severe diarrhea Blood in the urine or stools Trouble urinating

MEDICAL MANAGEMENT:

Chemotherapy is the primary treatment for each stage. Radiation to the brain and spinal cord is also administered in some cases. A bone marrow transplant is often recommended for relapsed ALL or in cases that cannot be induced into remission (refractory disease). It is also sometimes considered after remission is achieved for certain high-risk ALL types. The timing of bone marrow transplantation can be controversial, particularly after a first remission, although it has produced excellent long-term survival rates in appropriate patients. New drugs known as biological therapies are also being used.

NSG DX: Nursing Interventions Acute Lymphocytic Leukemia : Risk for Infection 1. Take action to prevent exposure to known or potential sources of infection:

Keep the protective insulation, according to institutional policy Maintain a careful hand washing technique Give good hygiene Limit visitors who were fever, flu or infections Give two times daily perianal hygiene and each bowel movement Limit fresh flowers and fresh vegetables Use the oral care protocol Hospitalized with neutropenic clients first.

Rational: Vigilance, minimizing client exposure to bacteria, viruses, and fungal pathogens either endogenous or exogenous.

2. Report if there are changes in vital signs Rationale: Changes in vital signs is an early sign of sepsis, especially if there is an increase in body temperature. 3. Get culture of sputum, urine, diarrhea, abnormal blood and body secretions as recommended Rational: The culture can confirm infection and identify the causative organism. 4. Explain the reasons for vigilance and abstinence Rational: The culture can confirm infection and identify the causative organism. 5. Reassure the client and his family that the increased susceptibility to infection while only Rational: granulocytopenia may persist 6-12 weeks. The notion of a temporary nature can help prevent anxiety granulocytopenia clients and their families 6. Minimize invasive procedures Rational: certain procedures may cause tissue trauma, increased susceptibility of infection.

ACUTE MYELOGENOUS LEUKEMIA DEF: lso known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare [1] disease, accounting for approximately 1.2% of cancer deaths in the United States, its incidence is expected to increase as the population ages. The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells,platelets, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Several risk factors and chromosomal abnormalities have been identified, but the specific cause is not clear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated. PATHO: The malignant cell in AML is the myeloblast. In normal hematopoiesis, the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will gradually mature into a mature white blood cell. In AML, though, a single myeloblast accumulates genetic changes which [27] "freeze" the cell in its immature state and prevent differentiation. Such a mutation alone does not cause leukemia; however, when such a "differentiation arrest" is combined with other mutations which disrupt genes controlling proliferation, the result is the uncontrolled growth of [28] an immature clone of cells, leading to the clinical entity of AML. Much of the diversity and heterogeneity of AML stems is because leukemic transformation can [29] occur at a number of different steps along the differentiation pathway. Modern classification

schemes for AML recognize the characteristics and behavior of the leukemic cell (and the leukemia) may depend on the stage at which differentiation was halted. Specific cytogenetic abnormalities can be found in many patients with AML; the types of [30] chromosomal abnormalities often have prognostic significance. The chromosomaltranslocations encode abnormal fusion proteins, usually transcription [31] factors whose altered properties may cause the "differentiation arrest". For example, in acute promyelocytic leukemia, the t(15;17) translocation produces a PML-RAR fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and [32] inhibits myeloid differentiation. The clinical signs and symptoms of AML result from the growth of leukemic clone cells, which tends to displace or interfere with the development of normal blood cells in the bone [33] marrow. This leads to neutropenia, anemia, and thrombocytopenia. The symptoms of AML are, in turn, often due to the low numbers of these normal blood elements. In rare cases, patients can develop a chloroma, or solid tumor of leukemic cells outside the bone marrow, which can cause various symptoms depending on its location. INCIDENCE: The incidence of AML increases with age. In the United States, the median age of patients with AML is 68 years. The age-adjusted population incidence is 17.6 per 100,000 for people older than 65 years, compared with 1.8 per 100,000 for those younger than 65 years. Similarly, chromosomal abnormalities occur with greater frequency among this older population of patients. TYPES:

ASSESSMENT: White blood cells fight infection. Low numbers can lead to fever and frequent infections. Red blood cells carry oxygen throughout the body. Low numbers can lead to anemia feeling tired or weak, being short of breath and looking pale. Platelets control bleeding. Low numbers can lead to easy bleeding or bruising and tiny red spots under the skin (petechiae). High numbers of leukemia cells may cause pain in the bones or joints. anemia bleeding bruising fever persistent weakness fatigue aches in bones and joints

swollen lymph nodes

MEDICAL MGMT: Chemotherapy drugs that destroy cancer cells or stop them from growing (described below). A bone marrow or cord blood transplant (described below). All-trans retinoic acid (ATRA) if he or she has the subtype of AML known as promyelocytic leukemia. Other newer treatments that were recently developed or are still being studied in clinical trials you can ask your doctor whether any newer treatments may be options for you.

NSG DX:

CHRONIC LMPHOCYTIC LEUKEMIA: DEF: B-cell chronic lymphocytic leukemia (B-CLL), also known as chronic lymphoid leukemia (CLL), is the most common type ofleukemia. Leukemias are cancers of the white blood cells (leukocytes). CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by producing antibodies. B cells grow out of control and accumulate

in the bone marrow and blood, where they crowd out healthy blood cells. CLL is a stage of small lymphocytic lymphoma (SLL), a type of B-cell lymphoma, which presents primarily in the lymph [1] nodes. CLL and SLL are considered the same underlying disease, just with different appearances. CLL is a disease of adults, but, in rare cases, it can occur in teenagers and occasionally in children (inherited). Most (>75%) people newly diagnosed with CLL are over the age of 50, and the majority are men. Most people are diagnosed without symptoms as the result of a routine blood test that returns a high white blood cell count, but, as it advances, CLL results in swollen lymph nodes, spleen, and liver, and eventually anemia and infections. Early CLL is not treated, and late CLL is treated with chemotherapy and monoclonal antibodie PATHO: The pathophysiology of lymphoma and leukaemia is defined by molecular biology. CLL cells are monoclonal B lymphocytes that express CD5, CD19, and CD23. These cell surface markers show an immunophenotype consistent with a mature activated B lymphocyte. Recent studies have also identified mutated immunoglobulin heavy chain (IgVH) and zetaassociated protein (ZAP-70) as important molecular markers. The presence of mutated IgVH gene is associated with slower disease progression and better prognosis. [10] [11] ZAP-70 is a tyrosine kinase that is essential for T-cell receptor signalling but is not found in normal B cells. Overexpression of ZAP-70 was found to correlate with unmutated IgVH and worse prognosis. [12] Another molecular marker of interest is CD38. CD38 expression correlates with presence of unmutated IgVH gene and denotes a poor-risk group INCIDENCE:

TYPES: The Rai system uses numbers 0 to IV to group CLL into low-, intermediate-, and high-risk categories. Generally, the higher the stage number, the more advanced the cancer. The Binet system uses letters A-C to stage CLL according to how many lymph node groups are involved and whether you have a drop in the number of red blood cells or platelets.

COMPLICATIONS: Autoimmune hemolytic anemia Bleeding from low platelet count Hypogammaglobulinemia, a condition in which you have lower levels of antibodies, which increases your risk of infection Idiopathic thrombocytopenic purpura (ITP) Infections that keep coming back (recur) Overwhelming fatigue Other cancers, including a much more aggressive lymphoma (Richters transformation) Side effects of chemotherapy

ASSESSMENT:

MEDICAL MANAGEMENT: Complete blood count (CBC) with white blood cell differential Bone marrow biopsy CT scan of the chest, abdomen, and pelvis Immunoglobulin testing Flow cytometry test of the white blood cells

NSG DX:

CHRONIC MYELOGENOUS LEUKEMIA: DEF: also known as chronic granulocytic leukemia (CGL), is a cancer of thewhite blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in thebone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors is the main finding. It is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome. CML is now largely treated with tyrosine kinase inhibitors (TKIs), such as imatinib (Gleevec/Glivec), dasatinib, or nilotinib, which have led to dramatically improved survival rates since their introduction in the last decade. PATHO: CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome. This chromosomal abnormality is so named because it was first discovered and described in 1960 by two scientists fromPhiladelphia, Pennsylvania, USA: Peter Nowell of the University of Pennsylvania and David Hungerford of Fox [5] Chase Cancer Center. In this translocation, parts of two chromosomes (the 9th and 22nd by conventional karyotypic numbering) switch places. As a result, part of the BCR ("breakpoint cluster region") gene from chromosome 22 is fused with the ABL gene on chromosome 9. This abnormal "fusion" gene generates a protein of p210 or sometimes p185 weight (p210 is short for 210 kDa protein, a shorthand used for characterizing proteins based solely on size). Because abl carries a domain that can add phosphate groups to tyrosine residues (a tyrosine kinase), thebcrabl fusion gene product is also a tyrosine kinase.

The fused BCR-ABL protein interacts with the interleukin 3beta(c) receptor subunit. The BCR-ABL transcript is continuously active and does not require activation by other cellular messaging proteins. In turn, BCR-ABL activates a cascade of proteins that control the cell cycle, speeding up cell division. Moreover, the BCR-ABL protein inhibits DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities. The action of the BCR-ABL protein is the pathophysiologic cause of chronic myelogenous leukemia. With improved understanding of the nature of the BCR-ABL protein and its action as a tyrosine kinase, targeted therapies (the first of which was imatinib mesylate) that specifically inhibit the activity of the BCRABL protein have been developed. These tyrosine kinase inhibitors can induce complete remissions in CML, confirming the central importance of bcr-abl as the cause of CML

INCIDENCE:

TYPES:

COMPLICATIONS: Blast crisis can lead to complications, including infection, bleeding, fatigue, unexplained fever, and kidney problems. Chemotherapy can have serious side effects, depending on the drugs used.

MEDICAL MANAGEMENT: 1. Targeted therapy with tyrosine kinase inhibitors. 2. High-dose therapy followed by allogeneic bone marrow transplant (BMT) or stem cell transplantation (SCT). 3. Biologic therapy with or without chemotherapy. 4. Hydroxyurea. 5. Splenectomy may be required and useful in patients having hematologic problems and physical discomfort from a massive spleen.

NSG DX:

NSG MANAGEMENT: