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ONLINE EXCLUSIVE
®
Nursing Implications of Mylotarg : A Novel
+
Antibody-Targeted Chemotherapy for CD33
Acute Myeloid Leukemia in First Relapse
Kathleen Shannon-Dorcy, RN, MN
Key Points . . .
Purpose/Objectives: To review the nursing implications of
gemtuzumab ozogamicin (Mylotarg®, CMA-676, Wyeth
Pharmaceuticals, Philadelphia, PA), a novel monoclonal
Acute myeloid leukemia (AML) is an aggressive disease; pa-
antibody-targeted chemotherapy agent for relapsed
tients with AML have a median survival of about one year.
acute myeloid leukemia (AML).
Data Sources: Published articles, abstracts, book chap-
Conventional chemotherapy for AML involves the use of cy-
ters, manufacturer information, unpublished clinical trial
totoxic drugs with significant side effects and possible he-
data, and personal experiences with gemtuzumab ozo-
matopoietic stem cell transplantation.
gamicin.
Data Synthesis: Conventional chemotherapy for AML is
Gemtuzumab ozogamicin is efficacious and well tolerated.
associated with toxicities that often limit treatment options
The infusion-related side effects are manageable with adher-
when AML relapses. Gemtuzumab ozogamicin is a human-
ence to guidelines of administration, premedication, and strict
ized recombinant anti-CD33 monoclonal antibody linked
patient monitoring.
to calicheamicin, a potent cytotoxic agent. The antibody
targets the CD33 antigen found on the surface of leukemic
blast cells and myeloid precursors. This targeting effect re-
duces the toxicity of gemtuzumab ozogamicin. The effi-
cacy and tolerability of gemtuzumab ozogamicin have
been documented in relapsed AML, particularly in patients
Goal for CE Enrollees
60 years of age or older, who often have no other treat-
ment options. As with other monoclonal antibody thera-
The goal of this continuing-education article is to further
pies, an "infusion syndrome" (i.e., fever and chills) may
enhance nurses' knowledge regarding gemtuzumab ozogami-
occur but can be managed effectively when administra-
cin.
tion guidelines are used.
Conclusions: Gemtuzumab ozogamicin is the first of a
Objectives for CE Enrollees
new class of targeted therapies for the treatment of re-
On completion of this CE, the participant will be able to
lapsed AML. A number of implications for nurses exist.
1. Describe treatment regimens currently available for the
Implications for Nursing: Nurses must be knowledgeable
treatment of acute myeloid leukemia.
about gemtuzumab ozogamicin preparation and admin-
istration, patient selection and monitoring, and intervention
2. Describe patient criteria to receive gemtuzumab ozogami-
procedures. This knowledge is necessary to accurately in-
cin.
form patients and their families of the possible course of
3. Discuss the nursing care of patients receiving gemtuzumab
treatment and potential side effects.
ozogamicin.
cute myeloid leukemia (AML) is a disease of the bone
A
marrow and is manifested by fatigue, infections, and
Kathleen Shannon-Dorcy, RN, MN, is a research nurse in the De-
bleeding caused by crowding and suppression of nor-
partment of Clinical Research at the Fred Hutchinson Cancer Re-
mal marrow precursors by malignant clones. The etiology of
search Center in Seattle, WA. She is a member of the Wyeth-Ayerst
AML is not known, but evidence suggests that AML is caused
Advisory Board and has spoken on its behalf, receiving honorariums
for those presentations. (Submitted March 2001. Accepted for pub-
by acquired genetic defects occurring in hematopoietic pre-
lication August 7, 2001.) (Mention of specific products and opinions
cursor cells. These early, mutated precursor cells give rise to
related to those products do not indicate or imply endorsement by the
progeny that fail to differentiate and continue to proliferate.
Oncology Nursing Forum or the Oncology Nursing Society.)
Inappropriate proliferation of myeloid blasts replaces normal
bone marrow, which reduces the production of normal red
Digital Object Identifier: 10.1188/02.ONF.E52­E59
ONF ­ VOL 29, NO 4, 2002
E52
blood cells (RBCs), white blood cells (WBCs), and platelets.
lowest incidence of leukemic relapse was achieved with allo-
A reduction in the production of these cells leads to anemia,
geneic HSCT during first CR; four- to five-year disease-free
neutropenia, and thrombocytopenia.
survival rates ranged from 50%­59%. However, many insti-
tutions place age limits for eligibility at 50­55 years because
Epidemiology and Natural History
treatment-related mortality from HSCT increases with age.
The percentage of patients who achieved second remissions
AML constitutes about 80% of all acute leukemia cases in
from chemotherapy regimens varied widely between studies,
adults. The annual incidence of AML is 2.7 per 100,000
generally ranging from 30%­80%, depending largely on the
people (Ries et al., 2000). This rate increases dramatically to
prognostic characteristics of the patients enrolled (Bassan et al.,
14.1 per 100,000 people older than 65 (Ries et al.). AML oc-
1998; Lee et al., 1998; Saito et al., 2000). However, these remis-
curs more commonly in adults than in children; the median
sions tended to be brief. Several agents, including amsacrine,
age at diagnosis is 68 years. Because the incidence of AML
mitoxantrone, high-dose cytarabine, and idarubicin, have dem-
increases with age, the number of new cases per year is pro-
onstrated activity in recurrent AML. These agents' potential
jected to increase. The five-year survival rate for patients
therapeutic results are limited by substantial levels of cardiac,
younger than 65 is about 25% but significantly lower--a rate
central nervous system, gastrointestinal, and hematologic tox-
of about 3%--for patients 65 or older (Ries et al.).
icities, as well as mucositis and alopecia. Therefore, treatment
AML is an aggressive disease. If left untreated, leukemic
with these agents often is not an option for many AML patients
myeloid cells will metastasize to the lymph nodes, spleen, and
60 or older or those in poor medical condition.
other vital organs. Most untreated or unresponsive patients
A novel drug, gemtuzumab ozogamicin (Mylotarg®, CMA-
will die within several months because of secondary infection
676, Wyeth Pharmaceuticals, Philadelphia, PA), is an anti-
or bleeding. Early symptoms of AML often resemble other
body-targeted chemotherapy agent that reduces potential tox-
conditions, making early diagnosis difficult.
icities by specifically targeting myeloid precursor cells. The
targeted nature and greater tolerability of gemtuzumab ozo-
Diagnosis and Treatment
gamicin provide a treatment opportunity for older patients
As a result of low RBC counts that are secondary to AML,
with relapsed AML.
patients with AML may present with fatigue and headaches.
Antibody-Targeted Chemotherapy
About one-third of these patients may have significant or near
life-threatening infections, usually of bacterial origin. In ad-
Clinical Rationale
dition, about one-third of patients have clinical signs of bleed-
ing, usually in the form of petechiae, ecchymoses, or epi-
With current conventional cytotoxic chemotherapies, re-
staxis. Bone marrow aspirates and biopsies are used to
mission rates are variable and depend on patients' ages, dura-
diagnose AML because the disease originates from hemato-
tion of the first CR, and response criteria, which vary by
poietic precursor cells.
study. Recent developments in antibody-targeted chemo-
When AML is diagnosed, the aggressive nature of the dis-
therapy suggest that an anti-CD33 antibody can target a che-
ease mandates that treatment begin immediately. The first
motherapeutic agent specifically to AML cells.
treatment goal is induction to obtain complete remission (CR).
Technical problems burdened initial attempts to use mono-
Once patients are stabilized (i.e., infections and hemorrhagic
clonal antibodies for targeted therapy. Patients' immune sys-
conditions are controlled), a combination of two drugs,
tems recognized the murine monoclonal antibodies as foreign
daunorubicin and cytarabine, most often is administered
and developed human antimouse antibodies (HAMA) that re-
(Masaoka, Ogawa, Yamada, Kimura, & Ohashi, 1996; Vogler
duced or eliminated the efficacy of the therapy (Schroff, Foon,
et al., 1992). About 60%­80% of patients treated with dauno-
Beatty, Oldham, & Morgan, 1985). New approaches to anti-
rubicin and cytarabine achieve CR (Schiller et al., 1992).
body-targeted therapy have overcome this limitation and have
However, the majority of patients relapse, with only 24%­
eliminated most of the HAMA response (Karius & Marriott,
44% of those younger than 60 and less than 20% of those 60
1997).
or older achieving durable remissions with postremission
Gemtuzumab Ozogamicin
therapy (Mayer et al., 1994). Early mortality during therapy
is the result of drug resistance with failure to respond to che-
Gemtuzumab ozogamicin is a targeted chemotherapy agent
motherapy or complications of myelosuppression.
composed of humanized anti-CD33 antibody linked to cali-
Current options for postremission therapy include short-
cheamicin, an antitumor antibiotic that binds to DNA and pro-
term, intensive treatment with cytarabine, dose-intensive
duces double-strand DNA breaks. Humanizing the antibody
cytarabine-based chemotherapy, and high-dose chemotherapy
was crucial to ensuring that the risk of HAMA formation was
with autologous or allogeneic hematopoietic stem cell trans-
minimized. Thus, 98.3% of the antibody was derived from a
plantation (HSCT) (Löwenberg, Downing, & Burnett, 1999).
human immunoglobulin gamma, and the remaining variable
The disease-free survival rate for patients treated with non-
region was derived from a murine antibody (hp 67.6, chemical
transplant postremission therapy is about 25%, with higher
compound) that binds CD33 (Wyeth Laboratories, 2000).
rates of disease-free survival observed in patients younger
Proposed mechanism of action: The CD33 antigen is a
than 60 (Champlin et al., 1990; Mayer et al., 1994).
cell marker that is expressed on the surfaces of normal and
Advances in induction therapy have resulted in improved
leukemic myeloid colony-forming cells but is not expressed
CR rates, with a majority of patients responding to initial che-
on pluripotent hematopoietic stem cells or nonhematopoietic
motherapy. Despite postremission therapy, however, CR is
cells. In addition, CD33 is expressed on the surfaces of leuke-
maintained only for a median of about one year (Preisler et al.,
mic blasts in more than 90% of patients with AML (Legrand
1989; Preisler, 1995). In a study by Tallman et al. (2000), the
et al., 2000). Binding the antibody portion of gemtuzumab
SHANNON-DORCY ­ VOL 29, NO 4, 2002
E53
ozogamicin to CD33 results in the formation of an antibody/
(16%) and pneumonia (7%). Treatment-related cardiotoxicity,
protein complex that is internalized and directed to the lyso-
cerebellar toxicity, and alopecia were not observed.
somes. The acidic pH in the lysosomes leads to the release of
All responding patients recovered from neutropenia to an ab-
solute neutrophil count of 500/ µm by a median of 41 days from
calicheamicin, which then binds to DNA, resulting in DNA
breaks and cell death by apoptosis.
the first dose of gemtuzumab ozogamicin (E.L. Sievers, per-
Pharmacokinetics: At the dose level of 9 mg/m2, detectable
sonal communication, May 14, 1999). Patients who received the
second dose of gemtuzumab ozogamicin less than 18 days af-
plasma concentrations of medication are present immediately
ter the first dose experienced a shorter duration of neutropenia.
after IV administration. The maximum plasma concentration,
About 30% of the patients had a moderate incidence of gen-
achieved shortly after the start of infusion, is 2.86 ± 1.35 mg/
erally transient grade 3 or 4 elevations of hepatic transami-
L (Korth-Bradley, Dowell, Berger, Liu, & King, 1999). The
nases or bilirubin. Clinically serious hepatic veno-occlusive
medication has a long half-life of 72 ± 42 hours. Plasma levels
disease occurred rarely (i.e., 2% of patients) after gemtu-
decrease with time, with an area under the curve of 123 ± 105
zumab ozogamicin therapy. A history of previous HSCT ap-
mg·hour/L. Results using flow microfluorometry indicate that
in patients who receive 9 mg/m2 gemtuzumab ozogamicin, 92%
peared to predispose patients to veno-occlusive disease after
of CD33 binding sites on peripheral blast cells are occupied
gemtuzumab ozogamicin therapy.
within 30 minutes (Sievers, Appelbaum, et al., 1999).
Phase I and II trials have demonstrated the efficacy and
Clinical experience: Phase I and II clinical trials have
safety of gemtuzumab ozogamicin. Given the fact that treat-
evaluated the ability of people with relapsed AML to tolerate
ment with gemtuzumab ozogamicin has a low incidence of se-
gemtuzumab ozogamicin. A phase I, ascending-dose study of
vere mucositis or alopecia, gemtuzumab ozogamicin is a ratio-
40 patients with relapsed and refractory AML examined the
nal choice for the treatment of older patients with AML. No
safety of gemtuzumab ozogamicin, using a regimen of as
important clinical differences were observed in these safety
many as three doses of gemtuzumab ozogamicin (0.25­9 mg/
endpoints between patients younger than 60 and those 60 and
m2) 14 days apart (Sievers, Appelbaum, et al., 1999). The
older. Gemtuzumab ozogamicin is a new treatment option for
study found that two doses of 9 mg/m2 given 14 days apart
patients with relapsed AML and is approved for patients 60 and
older who are not candidates for conventional chemotherapy.
was the most appropriate regimen for phase II trials.
Three international, phase II, open-label, single-arm,
Nursing Implications
multidose studies were conducted to assess the efficacy and
tolerability of gemtuzumab ozogamicin in patients with re-
Because gemtuzumab ozogamicin treatment is a new therapy,
lapsed AML (Sievers, Larson, et al., 1999). These studies in-
cluded 142 patients diagnosed with CD33+ AML with relapse
nurses should familiarize themselves with the issues and con-
cerns specific to the use of antibody-targeted chemotherapy, es-
confirmed by bone marrow biopsy or aspiration. All patients
pecially because some of these issues differ from those of con-
had CD33+ AML in first relapse following first CR of at least
ventional chemotherapy. Nurses should be aware of the proper
three months (for patients 60 and older) or six months (for pa-
tients younger than 60). Gemtuzumab ozogamicin (9 mg/m2)
method of administering the drug, be conscious of potential side
effects, and design a plan to anticipate and manage side effects.
was administered by IV infusion over a two-hour period, with
In addition, nurses should educate patients and their families
the two doses given 14 days apart. Patients were evaluated for
about the course of treatment, possible side effects, planned in-
28 days after the second dose to evaluate for potential toxici-
terventions for those side effects, and potential disease response.
ties and disease response to treatment.
The median age of patients treated with gemtuzumab ozo-
Patient Selection
gamicin was 53 years (Sievers, Larson, et al., 1999). Patients
Gemtuzumab ozogamicin is indicated for the treatment of
had a median remission duration of 11 months prior to gem-
patients with CD33+ AML in first relapse who are 60 or older
tuzumab ozogamicin treatment, and 94% had received prior
and are not considered candidates for conventional cytotoxic
postremission therapy. After one dose of gemtuzumab ozo-
chemotherapy. Therefore, it must be determined, usually by
gamicin, 43% of patients had 5% or less blasts in bone mar-
flow cytometry evaluation of the immunophenotype, that the
row. The overall remission rate for patients treated with two
AML is CD33+. Patients' WBC counts must be less than
doses of gemtuzumab ozogamicin was 30%.
30,000 cells/µL at the time of administration because higher
Treatment-emergent adverse events associated with gemtu-
WBC counts can result in severe acute respiratory distress
zumab ozogamicin were observed during the treatment period
syndrome (Wyeth Laboratories, 2000). Baseline complete
(i.e., the day of infusion to 28 days after the final dose). Chills,
blood counts, routine chemistry tests, and liver function tests,
fever, and occasional hypotension and dyspnea, which were ob-
including levels of aspartate aminotransferase (AST), alanine
served during infusion, are typical of antibody-based therapies
aminotransferase (ALT), and total bilirubin, also should be
(Winkler et al., 1999). Tumor lysis syndrome was reported oc-
determined. Finally, gemtuzumab ozogamicin has not been
casionally. Thrombocytopenia and neutropenia are expected
studied in patients with bilirubin greater than 2 mg/dL, and
with gemtuzumab ozogamicin treatment because the CD33 an-
caution should be exercised when administering gemtuzumab
tigen is present on hematopoietic precursor cells. Grade 3 or 4
ozogamicin to patients with hepatic impairment.
thrombocytopenia was observed in 99% of the patients; 97% ex-
perienced grade 3 or 4 neutropenia (Wyeth Laboratories, 2000).
Guidelines for Dosing and Administration
Grade 3 or 4 bleeding was observed in 15% of the patients, in-
Figure 1 offers nursing guidelines for the preparation and
cluding epistaxis (3%) and intracranial hemorrhage (4%). Only
administration of gemtuzumab ozogamicin. Because gemtu-
4% of the patients had grade 3 or 4 mucositis. In addition, 28%
zumab ozogamicin is sensitive to light, it must be protected
of the patients experienced grade 3 or 4 infections, including op-
from direct and indirect sunlight and fluorescent light during
portunistic infections. The most frequent infections were sepsis
ONF ­ VOL 29, NO 4, 2002
E54
include nausea, vomiting, and headache. As a precaution, most
Preparation
patients should receive prophylactic medications including
· Plan to start treatment early on the day of infusion.
diphenhydramine, acetaminophen, and IV fluids. Blood cul-
· Assess patients on the planned day of infusion. If they meet
tures and septic work-up should be taken according to institu-
all criteria (white blood cell count below 30,000 cells/µL,
tional policy. Patients experiencing chills should receive warm
CD33+ acute myeloid leukemia, liver function tests within nor-
blankets and be treated with 50 mg IV diphenhydramine. If
mal limits, and no active life-threatening infections), prepare
severe rigors persist, patients should be treated with IV meperi-
them for infusion and call pharmacy to request gemtuzumab
dine. If fever and chills persist, patients should be admitted to
ozogamicin.
· Gemtuzumab ozogamicin is light sensitive and must be mixed
an inpatient unit for continued observation and possible further
with the hood fluorescent lights off using standard chemo-
intervention. Hypotension can occur several hours after the end
therapy precautions.
of the infusion period, so an observation period is required to
· Place gemtuzumab ozogamicin in a minibag of normal sa-
prevent this from occurring away from clinical supervision.
line, which then should be placed in an opaque bag that
Grade 3 or 4 nonhematologic infusion-related adverse events
completely covers the minibag.
generally are rare but can include chills, fever, hypotension,
Administration
hypertension, hyperglycemia, hypoxia, and dyspnea. Fewer
· Administer 650­1,000 mg acetaminophen and 50 mg diphen-
infusion-related events, particularly those of grade 3 or 4 sever-
hydramine within one hour before start of infusion.
ity, are observed after the second dose.
· Administer normal saline before the start of infusion and con-
Separating drug-related effects from known leukemia com-
tinue for the length of infusion and for the four hours of moni-
plications is difficult. Table 3 lists common treatment-emergent
toring.
adverse events (Sievers, Larson, et al., 1999). Within 4­8 days
· Infuse gemtuzumab ozogamicin using a 1.2 micron in-line filter.
after infusion, patients may experience elevated total bilirubin,
· Infuse gemtuzumab ozogamicin 9 mg/m2 with a separate line
AST, and ALT levels. Abnormalities in liver function generally
over two hours using a volumetric pump or infusion controller.
are transient and reversible without intervention. Patients must
· Use gemtuzumab ozogamicin within about eight hours of mix-
ing. After eight hours, unused drug should be discarded.
be observed for elevated liver function. Total bilirubin, AST,
· Dispose of empty minibag using standard precautions.
and ALT levels should be monitored twice per week. Although
some patients have reported anorexia and low-grade nausea,
Figure 1. Guidelines for Dosage and Administration
these side effects generally have not required antiemetic
preparation and administration of the infusion. Before admin-
istration, patients should receive oral prophylactic medications
Table 1. Nursing Interventions
including 650­1,000 mg acetaminophen and 50 mg diphenhy-
dramine. Acetaminophen may be repeated every four hours
Side Effect
Nursing Interventions
throughout the infusion day. Treatment should be initiated by
Infusion syndrome
Administer oral acetaminophen and
and remain under the supervision of primary care providers
(i.e., fever and chills
diphenhydramine prior to infusion.
who are experienced in the use of cytotoxic chemotherapeutic
during and immedi-
Monitor vital signs
agents. Gemtuzumab ozogamicin may be administered on an
ately after infusion)
· At baseline and during infusion
outpatient basis, but patients should be monitored for clinically
· Before infusion
significant symptoms (e.g., fever, chills, rigor, nausea, vomit-
· Immediately after infusion
ing, hypotension) during the 4­6 hours immediately following
· Every hour for four hours.
the infusion. The recommended dose is a two-hour IV infusion
Admit patient if fever persists.
of 9 mg/m2. Shorter infusion schedules have not been tested. A
Chills and rigor
Instruct patient to wear warm clothes
second dose of gemtuzumab ozogamicin may be given 14 days
for infusion.
after the first infusion regardless of hematopoietic recovery but
Administer IV diphenhydramine and
may be postponed if patients have severe, life-threatening infec-
meperidine as ordered as needed.
tion or elevated liver function tests (i.e., total bilirubin at least
Wrap patient in warm blankets.
three times the upper limit of normal).
Increase ambient air temperature.
Admit patient if chills persist.
Patient Monitoring and Intervention
Nausea and vomiting
Administer antiemetics as ordered.
Patients should be monitored carefully throughout treatment
Assess dehydration and electrolyte
levels preinfusion and during course
with gemtuzumab ozogamicin. Table 1 reviews common side
of treatment.
effects and appropriate nursing interventions. Vital signs (i.e.,
Monitor nutritional status preinfusion
temperature, pulse, respiration, and blood pressure) should be
and during course of treatment.
taken at baseline, before infusion, as needed during infusion,
Hypotension
Monitor vital signs.
and immediately at the end of infusion. These measurements
Check for orthostatic tolerance every
should be repeated as needed for as long as four hours after
four hours.
treatment. Table 2 summarizes the acute infusion-related ad-
Monitor for tachycardia, dizziness,
verse events associated with gemtuzumab ozogamicin treat-
and shortness of breath.
ment (Wyeth Laboratories, 2000). Infusion-related symptoms
Administer fluids.
generally occur shortly after the two-hour infusion and are re-
Abnormal liver
Monitor aspartate aminotransferase,
solved within 2­4 hours with supportive therapy. Patients often
function tests
alanine aminotransferase, and total
experience severe chills and spiking fevers within four hours of
bilirubin levels twice a week.
infusion. Other common acute infusion-related adverse events
SHANNON-DORCY ­ VOL 29, NO 4, 2002
E55
Table 2. Acute Infusion-Related Adverse Events
suggest that patients bring warm clothes and any medications
that may be needed over the course of the day. Patients should
Any Severity
Grade 3 or 4
be assured that drug-related cardiac or cerebellar toxicities have
Adverse Event
(% of Patients)
(% of Patients)
not been reported with gemtuzumab ozogamicin treatment. The
frequency of severe mucositis and infections is lower with gem-
Chills
62
11
tuzumab ozogamicin compared with conventional chemo-
Fever
61
7
therapy. Also, gemtuzumab ozogamicin is not associated with
Nausea
<1
38
hair loss, a common side effect of conventional chemotherapy.
During the recovery period, patients may require blood prod-
Vomiting
32
<1
uct support and, therefore, need frequent monitoring of their
Headache
12
<1
complete blood cell counts.
Hypotension
4
11
Hypertension
6
3
Summary and Conclusions
Hypoxia
6
2
Dyspnea
1
4
AML is an aggressive disease of the bone marrow that oc-
curs more commonly in older adults. Patients present with
Hyperglycemia
2
2
life-threatening infections and bleeding and are diagnosed
Note. Based on information from Mylotarg® prescribing informa-
with AML when bone marrow biopsies reveal abnormal my-
tion (Wyeth Laboratories, 2000).
eloid production. Conventional chemotherapy treatment will
result in CR in 60%­80% of patients. However, even with
postremission therapy, 75% of patients eventually will re-
therapy. Nonetheless, patients should be counseled regarding
lapse. The lowest incidence of relapse is obtained when HSCT
the importance of maintaining adequate hydration and nutrition.
is used as postremission therapy. However, few older patients
During the treatment phase, myelosuppression is the major
can tolerate transplantation procedures.
toxicity. Figure 2 suggests guidelines for managing throm-
Gemtuzumab ozogamicin is a novel antibody-targeted che-
bocytopenia and infections in patients after gemtuzumab ozo-
motherapy agent that delivers a potent cytotoxic antitumor an-
gamicin treatment. Because of disease- and treatment-induced
tibiotic specifically to CD33+ myeloid cells. Phase I and II clini-
thrombocytopenia and infections, supportive care during
cal trials have established the safety and efficacy of gemtuzumab
gemtuzumab ozogamicin treatment may include platelet trans-
ozogamicin, and the drug has been approved for treatment of pa-
fusions and prophylactic broad-spectrum antibiotics, espe-
tients 60 and older in first relapse with CD33+ AML. The periph-
cially in febrile patients (Rebulla et al., 1997; Rubin, Hathorn,
eral WBC counts should be reduced to less than 30,000 cells/µL
& Pizzo, 1988).
prior to the initiation of gemtuzumab ozogamicin therapy.
Education
The most common infusion-related side effects are fever,
chills, and, less commonly, hypotension and dyspnea. These
To minimize treatment-associated anxiety, patients and their
families need a fundamental understanding of antibody-targeted
chemotherapy. Understanding infusion-related side effects, par-
ticularly fever, is key for patients preparing for treatment.
· Patients may experience profound thrombocytopenia requir-
Healthcare professionals should stress the frequent monitoring
ing platelet transfusions and occasional packed red blood
of body temperature during the period after the infusion as an
cell transfusions (this may occur within two days of infusion).
Check platelet levels within two days of infusion. Transfuse per
aid in early detection of infections. Patients must plan to spend
institutional policy for low platelet counts.
the entire day at the hospital or infusion clinic and make ar-
· Patients will have a rapid drop in neutrophil counts following
rangements to have others drive them home. Nurses should
infusion of gemtuzumab ozogamicin (absolute neutrophil
count may be 0 as early as day two after infusion).
· Perform complete blood counts at least three times per week
Table 3. Incidence of Grade 3 or 4 Treatment-Emergent
during neutropenia.
Adverse Events
· Instruct patients to take their temperature twice daily and
notify physician's office of elevation in temperature per insti-
Adverse Event
% of Patients
tutional policy.
· Administer prophylactic antibiotics per institutional policy for
Thrombocytopenia
99
absolute neutrophil count < 500 cells/µL.
Neutropenia
97
· Depending on their clinical status at the time of therapy,
Infections of any type
28
patients may be able to remain in the outpatient clinical set-
ting for the duration of treatment. However, as with other
Hyperbilirubinemia
23
chemotherapy regimens, patients may require hospitalization
Elevated liver function
17
if a fever of undetermined origin develops or if neutropenia
Sepsis
16
persists.
Fever
15
· Gemtuzumab ozogamicin does not appear to cross the
blood-brain barrier. Consequently, if patients have signs sug-
Bleeding
15
gesting leukemia involving the central nervous system (CNS),
Chills
13
a spinal tap should be performed and the patients should be
Nausea and vomiting
11
treated with therapy appropriate for CNS involvement.
Figure 2. Implications for Patient Care
Note. Based on information from Sievers, Larson, et al. (1999).
ONF ­ VOL 29, NO 4, 2002
E56
can be managed with appropriate nursing care, including the
The author acknowledges the contributions, first and foremost, of those
individuals who agreed to participate in the study; their courage in fac-
administration of antipyretic and antiemetic medications. As
ing leukemia is inspiring. She also acknowledges the nurses at the Fred
expected with this type of therapy, major adverse events with
Hutchinson Cancer Research Center, who worked together to implement
gemtuzumab ozogamicin are thrombocytopenia and neutrope-
the research protocols, and Sherry DeRoko, the clinical scientist who co-
nia. These can be managed with platelet infusions and broad-
ordinated the start of the pivotal Phase II protocol. She died of breast can-
spectrum antibiotics. Generally, transient elevations of hepatic
cer before the fruits of her labors were fully realized. Her dedication and
transaminases and bilirubin may occur. Treatment with gem-
scientific understanding built the foundation upon which we continue to
work.
tuzumab ozogamicin provides patients 60 and older, who oth-
erwise may not have an acceptable treatment option, with an
opportunity for remission of relapsed AML. With further re-
Author Contact: Kathleen Shannon-Dorcy, RN, MN, can be
search, gemtuzumab ozogamicin also holds promise for other
reached at 206-667-3648 or kshannon@FHCRC.org, with copy to
populations of people with AML.
editor at rose_mary@earthlink.net.
References
logiche Maligne dell'Adulto. New England Journal of Medicine, 337,
Bassan, R., Lerede, T., Buelli, M., Borleri, G., Bellavita, P., Rambaldi, A.,
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et al. (1998). A new combination of carboplatin, high-dose cytarabine,
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and cross-over mitoxantrone or idarubicin for refractory and relapsed
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acute myeloid leukemia. Haematologica, 83, 422­427.
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leukemia (AML) and previously untreated elderly patients with AML,
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secondary AML, and refractory anemia with excess blasts in transforma-
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(1992). Long-term outcome of high-dose cytarabine-based consolidation
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The continuing-education examina-
tion and test form for the preceding ar-
ticle appear on the following pages.
SHANNON-DORCY ­ VOL 29, NO 4, 2002
E57
ONF Continuing Education Examination
Nursing Implications of Mylotarg®: A Novel Antibody-Targeted
Chemotherapy for CD33+ Acute Myeloid Leukemia in First Relapse
b. To use nonpolyvinyl chloride tubing.
Credit Hours: 1.1
c. To cover the medication bag during administration.
Passing Score: 80%
d. To dilute the medication in a liter of normal saline.
Test ID #02-29/4-06
7.
Mr. Smith demonstrates understanding of his pretreat-
Test Processing Fee: $15
ment instructions when he
The Oncology Nursing Society is accredited as a provider
a. Drives himself to the clinic.
of continuing education (CE) in nursing by the
b. Dresses for the summer weather.
· American Nurses Credentialing Center's Commission on
c. Brings a list of his current medications.
Accreditation.
d. Schedules his appointment for early morning.
· California Board of Nursing, Provider #2850.
8.
Appropriate oral medications for side-effect prophylaxis
for Mr. Smith are
a. Ibuprofen and cimetidine.
CE Test Questions
b. Prochloperazine and lorazepam.
c. Dexamethasone and ondansetron.
1.
Gemtuzumab ozogamicin binds specifically with CD33,
d. Diphenhydramine and acetaminophen.
which is expressed on the surface of
Mr. Smith's body surface area is 2.5 m2. The appropriate
9.
a. Lymphocytes.
b. Pluripotent stem cells.
dose of gemtuzumab ozogamicin would be
c. Myeloid precursor cells.
a. 23.8 mg times two doses, 7 days apart.
d. Nonhematopoietic cells.
b. 20 mg times two doses, 14 days apart.
2.
Gemtuzumab ozogamicin is linked to a cytotoxic agent,
c. 22.5 mg times two doses, 14 days apart.
calicheamicin, classified as
d. 25 mg times three doses, 2 weeks apart.
a. A taxane.
10.
Mr. Smith is scheduled to receive his second dose, but it
b. An antimetabolite.
is held because
o
c. An alkylating agent.
a. He has a temperature of 38 C.
d. An antitumor antibiotic.
b. His blood counts have not recovered.
3.
Mr. Smith has been told that he is not eligible for conven-
c. His alanine aminotransferase (ALT) is 75 u/L.
tional chemotherapy for his acute myeloid leukemia. He
d. He recently completed antibiotics for pneumonia.
may meet criteria for gemtuzumab ozogamicin because
11.
When talking with Mr. Smith, a nurse should instruct him
he is a
that after his treatment he should
a. 58-year-old in first relapse.
a. Take his temperature twice a day.
b. 62-year-old in first relapse.
b. Avoid fresh fruits and vegetables.
c. 65-year-old in second relapse.
c. Take antiemetics around the clock.
d. 72-year-old with newly diagnosed AML.
d. Take antidiarrheal medication as needed.
4.
To finalize his eligibility for gemtuzumab ozogamicin,
12.
Following administration of gemtuzumab ozogamicin,
Mr. Smith first would undergo
Mr. Smith becomes dizzy, tachycardic, and short of
a. An abdominal ultrasound.
breath. He is likely experiencing
b. Cardiac assessment tests.
a. Hypotension.
c. Pulmonary function tests.
b. An allergic reaction.
d. Flow cytometry.
c. A transient ischemic attack.
5.
Which of the following laboratory results would cause
d. An acute myocardial infarction.
postponement of Mr. Smith's gemtuzumab ozogamicin
13.
During discharge instructions, a nurse should tell Mr.
treatment?
Smith
a. Bilirubin of 1.9 mg/dL.
a. To return to the clinic for weekly blood tests.
b. Hemoglobin of 8.6 g/dL.
b. That he is permitted to return to work as a farmer.
c. White blood cell count of 31,000 cells/µ L.
c. The signs and symptoms of bleeding and infection.
d. Platelet count of 15,000 cells/µ L.
d. How to self-administer subcutaneous injections of
6.
The most appropriate safety precaution to take with gem-
growth factors.
tuzumab ozogamicin is
14.
Mr. Smith complains of severe headaches and visual dis-
a. To administer it over one hour.
turbances. A nurse should tell him that
ONF ­ VOL 29, NO 4, 2002
E58
a. Computerized tomography of the brain will be or-
16. Mr. Smith calls the clinic complaining of a fever. He
dered to rule out a stroke.
should be instructed to
b. A spinal tap will be performed to assess for leukemic
a. Begin his injection of growth factors.
involvement of the central nervous system.
b. Report to the clinic for a septic work-up.
c. Gemtuzumab ozogamicin crosses the blood-brain bar-
c. Start his prescription for broad-spectrum antibiotics.
rier and can cause neurologic complaints.
d. Go to his primary care physician for physical assess-
d. An outpatient appointment has been made with a neu-
ment.
rologist to evaluate the cause of his symptoms.
17. When administering the second dose of gemtuzumab
15. Adverse events associated with gemtuzumab ozogamicin
ozogamicin, a nurse should instruct Mr. Smith that
may be observed the day of the infusion and as long as
a. The medication can be safely given over less time.
how many weeks later?
b. Nausea is more likely to occur with the second dose.
a. Six
c. His blood count will recover sooner than with the first
b. Four
dose.
c. Two
d. The side effects may be more severe because of cumu-
d. Three
lative effects.
Oncology Nursing Forum Answer/Enrollment Form
Nursing Implications of Mylotarg®: A Novel Antibody-Targeted Chemotherapy for CD33+ Acute Myeloid Leukemia
in First Relapse (Test ID #02-29/4-06)
4. The deadline for submitting the answer/enrollment form is
To receive continuing-education (CE) credit for this issue, simply
1. Read the article.
two years from the date of this issue.
2. Take the test and record your answers on the form below.
5. Contact hours will be awarded to registered nurses who suc-
Also, complete the program evaluation listed below. (You
cessfully complete the program. Successful completion is de-
may make copies of the answer form.)
fined as an 80% correct score on the examination and a com-
3. Mail the completed answer/enrollment form along with a
pleted program evaluation. Verification of your CE credit
check or money order for $15 per test payable to the Oncol-
will be sent to you. Certificates will be mailed within six
ogy Nursing Society. Payment must be included for your ex-
weeks following receipt of your Answer/Enrollment Form.
amination to be processed.
For more information, call 412-921-7373, ext. 296.
8.
9.
1.
5.
2.
6.
7.
4.
3.
a  10.
a
a
a
a
a
a
a
a
a
I n s t r u c t i o n s : Mark
b
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b
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b
b
b
b
b
b
your answers clearly by
c
c
c
c
c
c
c
c
c
c
placing an "x" in the
d
d
d
d
d
d
d
d
d
d
box next to the correct
answer. This is a stan-
11.
a  20.
a
a 18.
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a 12.
a 15.
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a 14.
dard form; use only the
b
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b
b
b
number of spaces re-
c
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c
quired for the test you
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are taking.
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Program Evaluation
1. How relevant were the objectives to the CE activity's goal?
2. How well did you meet the CE activity's objectives (see page E52)?
· Objective #1
· Objective #2
· Objective #3
3. To what degree were the teaching/learning resources helpful?
Too basic
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4. Based on your previous knowledge and experience, do you think
that the level of the information presented in the CE activity was
minutes
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My check or money order payable to the Oncology Nursing Society is enclosed. U.S. currency only. (Do not send cash.)
After completing this form, mail it to: Oncology Nursing Society, P.O. Box 3575, Pittsburgh, PA 15230-3575.
For more information or information on the status of CE certificates, call 412-921-7373, ext. 296.
SHANNON-DORCY ­ VOL 29, NO 4, 2002
E59