ACUTE MYELOID LEUKEMIA (AML)
AML results from a defect in the hematopoietic stem cell that dif-ferentiates into all myeloid cells: monocytes, granulocytes (neu-trophils, basophils, eosinophils), erythrocytes, and platelets. All age groups are affected; the incidence rises with age, with a peak incidence at age 60 years. AML is the most common nonlym-phocytic leukemia.
The prognosis is highly variable and is not consistently based on patient or disease variables. Patients with AML have a potentially curable disease. However, patients who are older or have a more undifferentiated form of AML tend to have a worse prognosis. Those who have preexisting MDS or who had previously received alkylating agents for cancer (secondary AML) have a much worse prognosis; the leukemia tends to be more resistant to treatment, re-sulting in a much shorter duration of remission. With treatment, these patients survive an average of less than 1 year, with death usu-ally a result of infection or hemorrhage. Patients receiving sup-portive care also usually survive less than 1 year, again dying from infection or bleeding.
Most of the signs and symptoms evolve from insufficient produc-tion of normal blood cells. Fever and infection result from neutropenia, weakness and fatigue from anemia, and bleeding ten-dencies from thrombocytopenia. The proliferation of leukemic cells within organs leads to a variety of additional symptoms: pain from an enlarged liver or spleen, hyperplasia of the gums, and bone pain from expansion of marrow.
The disorder develops without warning, with symptoms occurring over a period of weeks to months. CBC results show a decrease in both erythrocytes and platelets. Although the total leukocyte count can be low, normal, or high, the percentage of normal cells is usually vastly decreased. A bone marrow analysis shows an excess of immature blast cells (more than 30%).
AML can be further classified into seven different subgroups, based on cytogenetics, histology, and morphology (appearance) of the blasts. The actual prognosis varies somewhat between subgroups, but the clinical course and treatment differ substantially with only one subtype, acute promyelocytic leukemia (APL, or AML-M3). Patients with this leukemia often have significantly more problems with bleeding, in that they have underlying coagulopathy and a higher inci-dence of disseminated intravascular coagulation (DIC).
Complications of AML include bleeding and infection, the major causes of death. The risk of bleeding correlates with the level of platelet deficiency (thrombocytopenia). The low platelet count can result in ecchymoses (bruises) and petechiae (pinpoint red or pur-ple hemorrhagic spots on the skin). Major hemorrhages also may develop when the platelet count drops to less than 10,000/mm3. The most common sites of bleeding are gastrointestinal, pul-monary, and intracranial. For undetermined reasons, fever and in-fection also increase the likelihood of bleeding.
Because of the lack of mature and normal granulocytes, pa-tients with leukemia are always threatened by infection. The like-lihood of infection increases with the degree and duration of neutropenia; neutrophil counts that persist at less than 100/mm3 make the chances of systemic infection extremely high. As the du-ration of severe neutropenia increases, the patient’s risk for de-veloping fungal infection also increases.
The overall objective of treatment is to achieve complete remis-sion, in which there is no detectable evidence of residual leukemia remaining in the bone marrow. Attempts are made to achieve re-mission by the aggressive administration of chemotherapy, called induction therapy, which usually requires hospitalization for sev-eral weeks. Induction therapy typically involves high doses of cytarabine (Cytosar, Ara-C) and daunorubicin (DaunoXome) or mitoxantrone (Novantrone) or idarubicin (Idamycin); sometimes etoposide (VP-16, VePesid) is added to the regimen. The choice of agents is based on the patient’s physical status and history of prior antineoplastic treatment.
The aim of induction therapy is to eradicate the leukemic cells, but this is often accompanied by the eradication of normal types of myeloid cells. Thus, the patient becomes severely neutropenic (an ANC of 0 is not uncommon), anemic, and thrombocytopenic (a platelet count of less than 10,000/mm3 is common). During this time, the patient is typically very ill, with bacterial, fungal, and occasionally viral infections, bleeding, and severe mucositis, which causes diarrhea and a marked decline in the ability to maintain ad-equate nutrition. Supportive care consists of administering blood products (RBCs and platelets) and promptly treating infections. The use of granulocytic growth factors, either G-CSF (filgrastim [Neupogen]) or GM-CSF (sargramostim [Leukine]), can shorten the period of significant neutropenia by stimulating the bone mar-row to produce leukocytes more quickly; these agents do not ap-pear to increase the risk of producing more leukemic cells.
When the patient has recovered from the induction therapy (ie, the WBC and platelet counts have returned to normal and any infection has resolved), the patient typically receives consol-idation therapy (postremission therapy). The goal of consolida-tion therapy is to eliminate any residual leukemia cells that are not clinically detectable, thereby diminishing the chance for re-currence. Multiple treatment cycles of various agents are used, usually containing some form of cytarabine (eg, Cytosar, Ara-C). Frequently, the patient receives one cycle of treatment that is al-most the same, if not identical, to the induction treatment but uses lower dosages (therefore resulting in less toxicity).
Despite the aggressive use of chemotherapy, the likelihood of remaining in remission for a prolonged period is not great. About 70% of patients with AML experience a relapse (Hiddemann & Buchner, 2001). A recent study of long-term survival of patients with AML found that only 11% survived 10 years or longer (Micallef et al., 2001).
Another aggressive treatment option is bone marrow trans-plantation (BMT) or peripheral blood stem cell transplantation (PBSCT). When a suitable tissue match can be obtained, the pa-tient embarks on an even more aggressive regimen of chemother-apy (sometimes in combination with radiation therapy), with the treatment goal of destroying the hematopoietic function of the patient’s bone marrow. The patient is then “rescued” with the in-fusion of the donor stem cells to reinitiate blood cell production. Patients who undergo PBSCT transplantation have a significant risk for problems with infection, potential graft-versus-host dis-ease (in which the donor’s lymphocytes [graft] recognize the pa-tient’s body as “foreign” and set up reactions to attack the “foreign” host), and other complications. PBSCT has been shown to cure AML in 25% to 50% of patients who are at high risk for relapse or who have relapsed (Radich & Sievers, 2000).
Recent advances in understanding of the molecular biology of myeloid blast cells have resulted in a new therapeutic option. After the uncommitted stem cell differentiates into a myeloid stem cell, it expresses a specific antigen on the cell surface, called CD33. It appears that 90% of blast cells found in AML express CD33; nor-mal hematopoietic stem cells do not express this antigen (Radich
Sievers, 2000). Armed with that discovery, researchers developed a monoclonal antibody to target cells with the CD33 antigen. The anti-CD33 antibody is linked to a potent antitumor antibiotic, calicheamicin; this medication is called gemtuzumab ozogamicin (Mylotarg). When administered, the anti-CD33 antibody binds to cells with CD33 antigens, and the calicheamicin causes cell death. Normal myeloid and megakaryocyte precursors have the CD33 antigen, so the Mylotarg destroys them. Patients develop severe neutropenia and thrombocytopenia after receiving this medication. Nonetheless, Mylotarg shows promise as an effective agent against AML. In elderly patients, it appears to be somewhat less toxic than conventional induction therapy regimens.
Another important option for the patient to consider is sup-portive care alone. In fact, supportive care may be the only op-tion if the patient has significant comorbidity, such as extremely poor cardiac, pulmonary, renal, or hepatic function. In such cases, aggressive antileukemia therapy is not used; occasionally, hydroxyurea (eg, Hydrea) may be used briefly to control the in-crease of blast cells. Patients are more commonly supported with antimicrobial therapy and transfusions as needed. This treatment approach provides the patient with some additional time at home; however, death frequently occurs within months, typically from infection or bleeding.
The massive leukemic cell destruction from chemotherapy results in release of electrolytes and fluids within the cell into the systemic circulation. Increases in uric acid levels, potassium, and phosphate are seen; this process is referred to as tumor lysis syndrome. The increased uric acid and phosphorus levels make pa-tients vulnerable to renal stone formation and renal colic, which can progress to acute renal failure. Hyperkalemia and hypocalcemia can lead to cardiac dysrhythmias, hypotension, neuromuscular ef-fects such as muscle cramps, weakness, spasm/tetany, confusion, and seizure. Patients require a high fluid intake, alkalization of the urine, and prophylaxis with allopurinol to prevent crystallization of uric acid and subsequent stone formation. Gastrointestinal prob-lems may result from the infiltration of abnormal leukocytes into the abdominal organs and from the toxicity of the chemothera-peutic agents. Anorexia, nausea, vomiting, diarrhea, and severe mucositis are common. Because of the profound myelosuppressive effects of chemotherapy, significant neutropenia and thrombo-cytopenia typically result in serious infection and increased risk for bleeding.
Nursing management of the patient with acute leukemia is dis-cussed at the end of the leukemia section.
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