In contrast to ALL which develop in immature lymphocytes, most leukemia cells in CLL are fully mature, typically deriving from a malignant clone of B lymphocytes.
- Accumulation: One mechanism that results in this oncogenesis is that these cells do not go through the process of apoptosis (programmed cell death), leading ti an excessive amount of these cells accumulating in the marrow and circulation.
- Infiltration: Because these lymphocytes are small, they easily travel through the blood capillaries, often infiltrating and accumulating within the lymph nodes and spleen.

Incidence:

- CLL is a common malignancy of older adults, with an average age 72 years at diagnosis.
- CLL is the most prevalent time of adult leukemia in the Western world.

Progression/Survival Rate:

While many patients will have a normal life expectancy, others will have a very short life expectancy due to the aggressive nature of the disease.
- Prolymphocytic leukemia transformation: Around 10% of patients will experience a gradual transformation of their disease to one that becomes resistant to chemotherapy.
- Richter's transformation: Slightly fewer patients will experience Richter's transformation, which is a sudden transformation to a very aggressive lymphoma; this transformation results in markedly increased lymphadenopathy, splenomegaly, worsening B symptoms, and survival of only a few months despite treatment.

Causes/Risk Factors:

- Family Tendency: A strong familial predisposition exists with CLL; the disease can occur in 10% of those with a first- or second-degree relative with the same diagnosis.
- Toxin Exposure: Veterans of the Vietnam War who were exposed to Agent Orange may be at risk for developing CLL.

Clinical Manifestations:

Many symptoms are asymptomatic and diagnosed incidentally during routine physical examinations or during treatment for another disease.
- Lymphocytosis: An increased lymphocyte count (lymphocytosis) is always present.
- The erythrocyte and platelet count may be normal or, in later stages of the illness, decreased.
- Lymphadenopathy: Enlargement of the lymph nodes is common; can be severe and painful.
- Splenomegaly: Spleen may also be enlarged.
- B Symptoms: A constellation of symptoms including fevers, drenching sweats (especially at night), and unintentional weight loss.
- Impaired T-Cell Function: May result in tumor progression and increased susceptibility to second malignancies and infections.

Complications:

- Autoimmune complications can occur at any stage, as either autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura. In the autoimmune process, the reticuloendothelial system destroys the body's own erythrocytes of platelets.
- Infection: Life-threatening infections are particularly common with advanced disease, and account for 50% to 60% of all deaths in patients with CLL
- Patients with CLL have a greater risk for developing other cancers (risk is 2.2 times higher than the expected incidence per the SEER database); second cancers typically involve the skin, colon, lung, breast, prostate, and kidney; patients should receive an annual comprehensive skin examination as the incidence of skin cancer in patients with CLL is very high.

Assessment and Diagnosis:

- Immunophenotyping of the circulating B cells is critical to establish the diagnosis by identifying the presence of a malignant clone of these cells; it is also used to gauge the prognosis.
- Other special cytogenic and molecular analyses (e.g., fluorescence in situ hybridization [FISH]) are also used to guide prognosis and therapy.
- Beta-2 microglobulin, a protein found on the surface of lymphocytes, can be measured in the serum; an elevated level correlates with a more advanced clinical stage and poorer prognosis.

Medical Management:

Various parameters are considered when treatment is selected, including the clinical stage of the disease, disease-associated symptoms, the functional status of the patient, genetic risk for poor prognosis, and the extent of any prior therapy and efficacy of that therapy.
Functional status is a complex consideration: in the context, it incorporates the individual's life expectancy independent of CLL (due to other health problems), the ability to tolerate aggressive therapy (creatinine clearance is particularly important), and the ability to perform ADLs.
- Good Functional Status: Can typically tolerate aggressive therapy and often achieve lasting complete remission.
- Impaired Physical Status: Objective of treatment focuses on controlling bothersome symptoms (e.g., drenching night sweats; painful lymphadenopathy).

Pharmacologic Therapy:

Combination Therapy: Using an immunotherapeutic antibody against CD₂₀ with chemotherapy agents is typically given as initial therapy.
- When the disease is accompanied by a deletion of the TP₅₃ gene or a mutation of this gene, the combination of chemo-immunotherapy is largely ineffective; however, two kinase inhibitors are now available that are efficacious in this extent.

Surgical Management:

Because of the older age of most patients with CLL, transplantation may not be an option, particularly if significant comorbidities exist.

ALL progresses quickly, resulting from the uncontrolled proliferation of lymphocyte precursor cells, or lymphoblasts (stem cells - immature cells).
- Accumulation: Due to the precipitating factors, immature, non-functioning white blood cells appear to accumulate first in the tissue where they originate (e.g., lymphocytes in lymph tissue; granulocytes in bone marrow).
- Infiltration: These immature WBCs then spill into the bloodstream, traveling, and infiltrating other tissues.
- Malfunction: Eventually, this infiltration of immature WBCs results in organ malfunction as a result of their intrusion and hemorrhage.

Incidences:

- ALL is more common in males than females
- ALL is more common Caucasians, especially in people of Jewish descent.
- ALL is seen most often in children between the ages of 2 and 5, especially those who live in urban and industrialized areas (the most common form of cancer in children).
- While 80% of leukemias diagnosed in children aged 2 to 5 are ALL, ALL accounts for only about 20% of adult leukemia diagnoses.

Progression/Survival Rate:

ALL is very responsive to treatment.
- While the 5-year survival rate is >85% in children, the 3-year survival rate is <45% for adults.

Causes/Risk Factors:

- Congenital Disorders: Down syndrome, Bloom syndrome, Fanconi anemia, congenital agammaglobulinemia, and ataxia-telangiectasia usually predisposes ALL.
- Family Tendency: Genetics play a part in the development of ALL.
- Viruses: Since viral remnants have been found in leukemic cells, they may likely be a cause of ALL.

Clinical Manifestations:

Signs of acute lymphocytic leukemia may be gradual or sudden.
- High Fever: Elevated temperature accompanies by thrombocytopenia and abnormal bleeding, such as nosebleeds and gingival bleeding.
- Bruising: Easy bruising following minor trauma.
- Dyspnea: A decrease in mature blood cells leads to dyspnea.
- Anemia: Anemia is present in ALL due to the decrease in mature red blood cells.
- Fatigue: Patient will experience excess fatigue.
- Tachycardia: As the immature blood cells multiply and have difficulty carrying oxygen, the body compensates by pumping blood faster than usual.
- Pain: Pain from an enlarged liver or spleen, as well as bone pain is common.
The CNS is frequently a site for leukemic cells; thus, patients may exhibit cranial nerve palsies or headache and vomiting because of meningeal involvement.

Complications:

If left untreated, acute lymphocytic leukemia is fatal; usually due to complications resulting from leukemic cell infiltration of the bone marrow and other vital organs.
- Infection: Immature WBCs are unable to defend the body against invading pathogens, leaving the patient immunocompromised and at great risk for infection.
- Organ Malfunction: Infiltration of immature WBCs into the bloodstream and tissues, results in organ malfunction as a result of their intrusion and hemorrhage.

Assessment and Diagnostic Findings:

Diagnosis of ALL can be confirmed with a combination of the following:
- Bone Marrow Aspiration: Typical clinical findings and bone marrow aspirate showing a proliferation of immature WBCs confirm ALL.
- Bone Marrow Biopsy: A bone marrow biopsy, usually of the posterior superior iliac spine, is part of the diagnostic workup.
- Blood Counts: Blood counts show severe anemia, thrombocytopenia, and neutropenia.
- Differential Leukocyte Count: Differential leukocyte count determines cell type.
- Lumbar Puncture: Lumbar puncture detects meningeal involvement.
- Uric Acid Levels: Elevated uric acid levels and lactic dehydrogenase levels are commonly found.

Medical Management:

The goal of treatment is to obtain remission without excess toxicity and with a rapid hematologic recovery so that additional therapy can be given if needed.
- Systemic Chemotherapy: Systemic chemotherapy aims to eradicate leukemic cells and induce remission (<5% of blast cells in the marrow and peripheral blood are normal).
- Platelet Transfusion: Platelet transfusion is performed to prevent bleeding.
- Red Blood Cell Transfusion: RBC transfusion is performed to prevent anemia.

Pharmacologic Therapy:

The following are drugs included in chemotherapy used to treat ALL:
- Vincristine: Vincristine is an anti-cancer (antineoplastic or cytotoxic) chemotherapy drug and is classified as a plant alkaloid.
- Prednisone: This drug works by altering the body's normal immune system responses.
- Cytarabine: Cytarabine belongs to the category of chemotherapy called antimetabolites, wherein when the cells incorporate these substances into the cellular metabolism, they are unable to divide and they attack cells at very specific phases in the cycle.
- L-asparaginase: Asparaginase breaks down asparagine in the body, so since the cancer cells cannot make more asparagine, they die.
- Daunorubicin: Daunorubicin is classified as an antitumor antibiotic that is made from natural products produced by species of the soil fungus Streptomyces, and these drugs act during multiple phases of the cell cycle and are considered cell-cycle specific.
- Antibiotics; Antifungals; Antivirals: These control infection, a common complication of acute leukemias.

Surgical Management:

Aggressive treatment of ALL may include surgical intervention.
- Bone Marrow Transplant
- Stem Cell Transplant: One of the latest developments in the treatment of leukemias.

Nursing Management:

The care plan for the leukemic patient should emphasize comfort, minimize the adverse effects of chemotherapy, promote preservation of veins, manage complications, and provide teaching and psychological support.
Goals:
- Absence of pain.
- Attainment and maintenance of adequate nutrition.
- Activity tolerance.
- Ability to provide self-care and to cope with diagnosis and prognosis.
- Positive body image.