A. Nonneoplastic Disorders of WBC 1. Neutropenia 2. Infectious Mononucleosis B. Neoplastic Disorders of Hematopoietic and Lymphoid Origin 1. Malignant Lymphomas 2.

Leukemias 3. Plasma Cell Dyscrasia

Leukocytosis

* Abnormally elevated number of white blood cells *Abnormally low number of white blood cells.

Leukopenia

Thrombocytosis

*Abnormally elevated number of platelets. *Abnormally low number of platelets.

Thrombocytopenia

Polycythemia

* Abnormally elevated number of red blood cells. * Abnormally low number of red blood cells

Anemia

Literally white blood, is a neoplastic proliferation of one particular cell type (granulocytes, monocytes, lymphocytes, or megakaryocytes). The defect originates in the hematopoietic stem cell, either the myeloid, or the lymphoid stem cell.

Based on Development Rate of Symptoms: Acute leukemia -the onset of symptoms is

abrupt, often occurring within a few weeks. WBC development is halted at the blast phase, so that most WBCs are undifferentiated or are blasts.

Chronic Leukemia symptoms evolve over a period of months to years, and the majority of WBCs produced are mature. Chronic leukemia progresses more slowly; the disease trajectory can extend for years.

Based on Predominant Cell Type: Lymphocytic leukemias involve immature lymphocytes that originate in the bone marrow but infiltrate the spleen, lymph nodes, CNS, and other tissues.

Myelogenous leukemias, which involve the

myeloid stem cells in bone marrow, interfere with the maturation of all blood cells, including the granulocytes, erythrocytes, and thrombocytes.

Acute Leukemia affects immature cells and are characterized by rapid progression of symptoms. 1. Acute Lymphocytic Leukemia (ALL) When lymphocytes are the predominant malignant cells. 2. Acute Myelogenous Leukemia (AML) When immature monocytes or granulocytes are predominant malignant cells.

1. Associated with:
Exposure to ionizing radiation. Exposure to certain chemicals and toxins (benzene, alkylating agents) Familial susceptibility. Genetic disorders (Down syndrome, Fanconi's anemia).

2. Half of new leukemias are acute. 85% of acute leukemias in adults are AML. ALL - most common in children (ages 2 and 9 3. Childhood ALL is usually cured with chemotherapy alone (> 75%), whereas only 30% to 40% of adults with ALL are cured. 4. AML - older people (median age - 67). Patients younger than age 60 - AML is difficult to treat (median survival of 5 to 6 months) despite intensive therapy.

Common symptoms include pallor, fatigue, weakness, fever, weight loss, abnormal bleeding and bruising, lymphadenopathy (in ALL), and recurrent infections (in ALL). Other presenting symptoms may include bone and joint pain, headache, splenomegaly, hepatomegaly, neurologic dysfunction.

CBC and blood smear - peripheral WBC count varies widely from 1,000 to 100,000/mm3; abnormal immature (blast) cells; profound anemia; low platelet count Bone marrow aspiration and biopsy- bone marrow is full of leukemic cells (immature cells that are dividing) Lymph node biopsy to detect spread. Lumbar puncture and examination of cerebrospinal fluid for leukemic cells (ALL)

ACUTE LEUKEMIA: 1. To eradicate leukemic cells and allow restoration of normal hematopoiesis.

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 Induction therapy intense started at the time of diagnosis to achieve a rapid, complete remission of all manifestations of disease 1. Antimetabolite: Cytarabine (ARA-C, Cytosar-U) 2. Antibiotic: Daunorubicin (Cerubidine) Doxorubicin (Adriamycin PFS)

- Consolidation therapy- often consists of another course of either the same drugs used for induction at a different dosage or a different combination of chemotherapy drugs. Maintenance therapy maybe prescribed for months to years after successful induction and consolidation therapies purpose is to maintain the remission achieved through induction and consolidation.
- Used for ALL and APL

Leukostasis: high numbers (>50,000/mm3) of circulating leukemic cells (blasts), blood vessel walls are infiltrated and weakened (high risk of rupture, bleeding, intracranial hemorrhage) Disseminated intravascular coagulation (DIC). Tumor lysis syndrome: rapid destruction of large numbers of malignant cells leads to alterations in electrolytes (hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia). Renal failure and other complications. Infection, bleeding, organ damage.

Weight loss, fever, frequency of infections, progressively increasing fatigability, shortness of breath, palpitations, visual changes(retinal bleeding) Difficulty in swallowing, coughing, rectal pain. Enlarged lymph nodes, hepatosplenomegaly, evidence of bleeding, abnormal breath sounds, skin lesions. Infection: mouth, tongue, and throat for reddened areas or white patches. Skin for breakdown, which is a potential source of infection.

Pain related growth of tumor, infection or sideeffects of chemotherapy Powerlessness related to diagnosis and perceived lack of support/resources Risk for Infection related to granulocytopenia of disease and treatment (chemotherapy/radiation) Risk for Injury related to bleeding secondary to bone marrow failure and thrombocytopenia

Pain will be controlled Patient and family will be empowered to seek appropriate help Risk of infection will be minimized Risk of bleeding will be minimized

Controlling Pain: Assess at least every 4 hours for presence, location, intensity, and characteristics of pain. Teach and use nonpharmacologic measures, such as the use of music, relaxation breathing, progressive muscle relaxation, distraction and imagery to help manage pain. Administer analgesics on regular schedule as ordered (Avoid aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) in thrombocytopenic patients; If oral analgesics not effective- I.V. route)

Empowering patient and family Encourage verbalization of feelings regarding diagnosis, treatment plan, and anticipated course of illness. Refer as needed to social worker, psychiatric liaison nurse, psychologist. Share information regarding national and local resources.

Preventing Infection Monitor 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 mouth; redness, swelling, heat or pain of eyes, ears, throat, skin, joints, abdomen, rectal and perineal areas; cough, changes in sputum; skin rash.

Preventing Infection 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:
Avoid diarrhea and constipation, which can irritate the rectal mucosa; Avoid use of rectal thermometers; Keep perianal area clean.

Preventing Infection Care for patient in private room with strict handwashing practice. Patients with prolonged neutropenia may benefit from HEPA filtration. Encourage and assist patient with personal hygiene, bathing, and oral care. Obtain cultures and administer antimicrobials promptly as directed and prescribed.

Preventing and Managing Bleeding 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.

Preventing and Managing Bleeding Test all urine, stool, emesis for gross and occult blood. Monitor platelet counts daily. Administer blood components as directed and prescribed. Keep patient on bed rest during bleeding episodes.

Patient Education and Health Maintenance Teach infection precautions 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 perianal care. Teach bleeding precautions Encourage regular dental visits to detect and treat dental infections and disease.

Pain is reduced/minimized Appropriate verbalizations of feelings Afebrile, without signs of infection No signs of bleeding

are malignancies involving the proliferation of well-differentiated myeloid and lymphoid cells. Chronic Myelogenous Leukemia(CML) (involving more mature cells than acute leukemia) - proliferation of myeloid cell lines, including granulocytes, monocytes, platelets and occasionally RBCs. Chronic Lymphocytic Leukemia(CLL) (involving more mature cells than acute leukemia) proliferation of morphologically normal but functionally inert lymphocytes that include B cell (95% of cases), T cell

Chronic Myelogenous Leukemia (CML) Specific etiology unknown, associated with exposure to ionizing radiation and family history of leukemia. First cancer associated with chromosomal abnormality ( Philadelphia[Ph] chromosome), > 90% of patients. Accounts for 25% of adult leukemias and less than 5% of childhood leukemias. Generally presents between ages 25 and 60 with peak incidence in the mid-40s.

Chronic Myelogenous Leukemia (CML) Insidious onset, may be discovered during routine physical examination. Insidious symptoms, such as malaise, anorexia, and weight loss Common symptoms: shortness of breath; enlarged spleen and liver There are three stages in CML:
chronic, transformation, and accelerated or blast crisis.

1. CBC and blood smear: large numbers of granulocytes CML(>100,000/mm3) platelets may be decreased 2. Bone marrow aspiration and biopsy: CML: hypercellular, usually demonstrates Philadelphia (Ph1) chromosome.

Chronic Lymphocytic Leukemia (CLL) Specific etiology unknown. Tends to cluster in families, much more common in Western hemisphere. Male hormones may play role. Most common adult leukemia in United States and Europe. Disease of later years (90% over age 50); twice as common in men than in women. Lymphocytes are immunoincompetent and respond poorly to antigenic stimulation. In late stages, organ damage may occur from direct lymphocytic infiltration of tissue. May be indolent for years, with gradual transformation to more malignant disease.

Chronic Lymphocytic Leukemia (CLL) Insidious onset, may be discovered during routine physical examination. Early symptoms: history of frequent skin or respiratory infections, symmetrical lymphadenopathy, mild splenomegaly. More advance: pallor, fatigue, activity intolerance, easy bruising, skin lesions, bone tenderness, abdominal discomfort.

1. CBC and blood smear: CLL (10,000 to 150,000/mm3); anemia, thrombocytopenia, hypogammaglobulinemia. 2. Bone marrow aspiration and biopsy: CLL: lymphocytic infiltration of bone marrow. 3. Lymph node biopsy to detect spread.(CLL)

Chronic Phase - 10% blasts in their blood or bone marrow samples. These patients usually have fairly mild symptoms (if any) and usually respond to standard treatments.
Most patients are diagnosed in the chronic phase.

Accelerated Phase The bone marrow or blood samples have more than 10% but fewer than 20% blasts High blood basophil count (basophils making up at least 20% of the white blood cells) High white blood cell counts that do not go down with treatment Very high or very low platelet counts that are not caused by treatment New chromosome changes in the leukemia cells

Blast Phase
Bone marrow and/or blood samples from a patient in this phase have more than 20% blasts.

A. Chronic Phase 1. Imatinib (Gleevec) providing a highly effective oral treatment for newly diagnosed patients and in chronic or accelerated phases (protein-tyrosine kinase inhibitor inhibit proliferation of abnormal cells and inducing cell death (apoptosis) in abnormal cells. 2. Intolerance to imatinib mesylate, Alpha Interferon - eliminates the Ph1 chromosome and blasts

A. Chronic Phase (2) 3. Allogeneic (related or unrelated donor) Bone Marrow Transplantation. 4. Palliative treatment, controlling symptoms, includes chemotherapy with such agents as busulfan (Myleran) or hydroxyurea (Hydrea); irradiation; splenectomy. B. Accelerated phase or blast crisis 1. High dose chemotherapy, leukophoresis 2. Supportive care generally terminal

A. Symptom Control and Treatments 1. Newly diagnosed CLL is generally observed and followed closely until symptoms develop. 2. Lymphocyte proliferation can be suppressed with chlorambucil (Leukeran), cyclophosphamide (Cytoxan), and prednisone (Orasone). 3. B cell CLL may be treated with fludarabine (Fludara). 4. Monoclonal antibodies such as alemtuzumab (Campath) and rituximab (Rituxan) may be used.

A.

Symptom Control and Treatments 5. Splenic irradiation or splenectomy for painful splenomegaly or platelet sequestration, hemolytic anemia. 6. Irradiation of painful enlarged lymph nodes. 7. Bone marrow transplant and combinations of alpha interferon and interleukin-2 are also used to treat CLL.

B. Supportive Care Transfusion therapy to replace platelets and RBCs. Antibiotics, antivirals, and antifungals as needed to control infections. I.V. immunoglobulins or gamma globulin to treat hypogammaglobulinemia. Irradiation of painful enlarged lymph nodes. Bone marrow transplant and combinations of alpha interferon and interleukin-2 are also used to treat CLL.

Chronic Myelogenous leukemia (CML) fatigue, weight loss, night sweats, activity intolerance. Signs of bleeding and infection. Splenomegaly, hepatomegaly. Weight gain and edema in patients taking imatinib.

Chronic Lymphocytic Leukemia (CLL) History of infections, fatigue, bruising and bleeding, swollen lymph nodes. Signs of anemia, bleeding, or infection. Splenomegaly, hepatomegaly, lymphadenopathy.

Fear related to disease progression and death Acute pain related to tumor growth, infection, or adverse effects of chemotherapy Activity Intolerance related to anemia and adverse effects of chemotherapy

Patient will manage fear and demonstrate effective coping skills Pain will be controlled To increase activity tolerance

Allaying Fear Encourage appropriate verbalization of feelings and concerns. Provide comprehensive teaching about disease, using methods and content appropriate to patient's needs. Assist patient in identifying resources and support (eg, family and friends, spiritual support, community or national organizations, support groups). Facilitate use of effective coping mechanisms.

Controlling Pain: Assess at least every 4 hours for presence, location, intensity, and characteristics of pain. Teach and use nonpharmacologic measures, such as the use of music, relaxation breathing, progressive muscle relaxation, distraction and imagery to help manage pain. Administer analgesics on regular schedule as ordered (Avoid aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) in thrombocytopenic patients; If oral analgesics not effective- I.V. route)

Improving Activity Tolerance Encourage frequent rest periods alternating with ambulation and light activity as tolerated. Assist patient with hygiene and physical care as necessary. Encourage balanced diet or nutritional supplements as tolerated. Teach patient to use energy conservation techniques while performing activities of daily living, such as sitting while bathing, minimizing trips up and down stairs, using bag or cart to carry articles.

Patient Education and Health Maintenance Teach patient to take medications as prescribed and monitor for adverse effects. Teach patient method of subcutaneous injection for self-administration of alpha interferon, and teach strategies for managing such adverse effects as fatigue and fevers. Provide patient and family with information about resources in the community, such as the Leukemia and Lymphoma Society

Patient Education and Health Maintenance Teach patient to minimize risk of infection Teach patient to take medications as prescribed and monitor for adverse effects. avoid aspirin and NSAIDs, which interfere with platelet function. Teach patient method of subcutaneous injection for self-administration of alpha interferon, and teach strategies for managing such adverse effects as fatigue and fevers. Provide information about resources in the community, such as the Leukemia Society

Demonstrates effective coping skills and manages fear Verbalizes absence of pain Performs activities without complaints of fatigue