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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