1_Acute Leukemia Diagnosis and Treatment_2019

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Seminars in Oncology Nursing 35 (2019) 150950
Contents lists available at ScienceDirect
Seminars in Oncology Nursing
journal homepage: https://www.journals.elsevier.com/seminars-in-oncology-nursing
Acute Leukemia: Diagnosis and Treatment
Lisa M. Blackburn, MS, RN, AOCNS�,*, Sarah Bender, MS, RN, CNP, OCN�,
Shelly Brown, MS, APRN-CNS, AOCNS�
The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
A R T I C L E I N F O
*Address correspondence to: Lisa M. Blackburn, MS, RN
cialist, The Ohio State University Comprehensive Cancer
cer Hospital and Richard J. Solove Research Institute, 46
43210.
E-mail address: lisa.blackburn@osumc.edu (L.M. Black
https://doi.org/10.1016/j.soncn.2019.150950
0749-2081/© 2019 Elsevier Inc. All rights reserved.
A B S T R A C T
Objective: To provide an overview of acute leukemia, comparing incidence, presenting symptoms, diagnosis,
prognosis, and treatment of the major subtypes.
Data Sources: Review of articles dated 2010 to present in PubMed and CINAHL, and National Comprehensive
Cancer Network Guidelines.
Conclusion: The diagnosis of acute leukemia is comprised of a variety of hematopoietic neoplasms that are
both complex and unique. Each subtype of acute leukemia has defining characteristics that affect prognosis
and treatment.
Implications for Nursing Practice: Nurses play an integral role in the care of the patient with acute leukemia
during and beyond hospitalization. Therefore, baseline knowledge of these diseases is essential. Early symp-
tom recognition is central in the management of oncologic emergencies.
© 2019 Elsevier Inc. All rights reserved.
Key Words:
leukemia
hematology
hematopoiesis
differentiation
induction therapy
consolidation therapy
oncologic emergencies
, AOCNS� , Clinical Nurse Spe-
Center, Arthur G. James Can-
0 W. 10th Ave., Columbus, OH
burn).
Introduction
The term leukemia is derived from the Greek words “leukos” and
“heima,” which refer to excess white blood cells (WBC) in the body.
Leukemia, once considered a single disease, was first recognized
around the 4th century.1 By the end of the 19th century, leukemia
was classified into four subtypes: acute myeloid leukemia (AML),
acute lymphocytic leukemia (ALL), chronic myeloid leukemia, and
chronic lymphocytic leukemia. Currently, the diagnosis of leukemia
is known to be comprised of a variety of hematopoietic neoplasms
that are both complex and unique. Each subtype can be further dis-
tinguished by morphologic differences, cytogenetic abnormalities,
immunophenotype, and clinical features.1 These distinguishing char-
acteristics affect both prognosis and selection of optimal treatment.
This review will focus only on those classified as acute leukemia.
Acute Myeloid Leukemia
Etiology/incidence
Acute myeloid leukemia (AML) is a disorder of hematopoietic progen-
itor cells characterized by an increased number of immature myeloid
cells in the bone marrow.1,2 AML is the most common acute leukemia in
adults, with an incidence of 2.7 per 100,000 people, or about 21,000 cases
per year in the US.3 There are 14 new cases of leukemia per 100 people
per year and roughly 1.6% of men and women will be diagnosed during
their lifetime.3 The median age at diagnosis is 68 years, with 55.54% of
patients diagnosed at 65 years or older.3 Although it varies by subtype
and other risk factors, the 5-year survival rate is 62.7%.3 With the aging
population, the incidence of AML has been rising 2.2% per year over the
past 10 years.1 The cause of AML remains largely unknown. The following
environmental factors have been associated with the diagnosis: ionizing
radiation, benzene, chemotherapy drugs, and tobacco.2 Other disorders
involving myeloid and nonmyeloid cells, such as chronic myelogenous
leukemia, primary myelofibrosis, essential thrombocytosis, polycythemia
vera, paroxysmal nocturnal hemoglobinuria, and aplastic anemia, can
evolve into AML. Bloom syndrome, Diamond-Blackfan syndrome, Down
syndrome, Fanconi anemia, neurofibromatosis, and Noonan syndrome
are all genetic conditions associated with AML.2
There is an increased risk of treatment-related AML in survivors of
childhood and young adult cancers.4 The exact incidence of treatment-
related AML is unknown, but it is estimated that therapy-related AML
may occur in 5% to 20% of patients with AML.4 The rate of therapy-
related AML is higher among patients treated for breast and gyneco-
logic cancers and non-Hodgkin and Hodgkin lymphoma. This is likely
because of the cytotoxic agents commonly used to treat these cancers
(eg, anthracyclines, topoisomerase inhibitors, and alkylating agents).4
Clinical Presentation
As with other leukemias, patients often present to their primary care
clinician, local urgent care, or emergency department with non-specific
mailto:lisa.blackburn@osumc.edu
https://doi.org/10.1016/j.soncn.2019.150950
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Table 1
Cytogenetic and molecular prognostic factors in acute myelogenous leukemia (AML).
Risk category Cytogenetics Molecular abnormalities
Favorable risk t(8;21)(q22;q22.1)
inv(16)(p13.1q22) or t
(16;16)(p13.1;q22)
RUNX1-RUNX1T1
CBFB-MYH11
Mutated NRM1 w/o FLT3-
ITD or with FLT3-ITDlow
Biallelic mutated CEBPA
Intermediate risk T(9;11)(p21.3;q23.3)
Cytogenetic abnormalities
not in other category
Mutated NPM1 and
FLT3ITDhigh
Wild-tpye NPM1 w/o
FLT3-ITD or with FLT3-
ITDlow
MLLT3-KMT2A
Poor risk T(6;9)(p23;q34.1)
T(v;11q23.3)
T(9;22)(q34.1;q11.2)
inv(3)(q21.3q26.2) or t(3;)
(q21.3;q26.2)
-5 or del(5q); -7; -17/abn
(17p)
DEK-NUP214
KMT2A rearranged
BCR-ABL1
GATA2, MECOM(EVI1)
Complex karyotype
Wild-type NPM1 and
FLT3-ITDhigh
Mutated RUNX1
Mutated ASXL1
Mutated TP53#
Data from Estey,14 Rockova et al,15 and O’Donnell.16
2 L.M. Blackburn et al. / Seminars in Oncology Nursing 35 (2019) 150950
chief complaints andmay be treated for general symptommanagement.
Symptoms are typically a result of the highly proliferative, malignant
“blasts” (the immature leukemic cells) invading the bonemarrowwhere
healthy cells are normally produced. Anemia, leukopenia, and thrombo-
cytopenia occur because of the lack of space for cells to grow and
mature into healthy red cells, WBC, and platelets. With anemia comes
fatigue, shortness of breath with normal activity, chest pain, dizziness,
and pallor. Fever, frequent infections, and impaired wound healing are a
result of WBC dysfunction and leukopenia.5
Patients with thrombocytopenia often present with bleeding that is
difficult to stop, easy bruising, nose bleeds, petechiae, and females may
also notice menstruation that lasts longer than usual.2,6�8 Patients may
present with arthralgias as a result of leukemia infiltration into the bone
marrow.2,7 Patients can also present with leukocytosis manifesting as
lymphadenopathy, splenomegaly, and hepatomegaly.6,8 Signs and
symptoms of AML are related to the underlying disruption in hemato-
poiesis because of the untreated disease. Patients may present with
physical signs of extramedullary disease, such as skin lesions, gingival
hypertrophy, or lymphadopathy.2
Hyperleukocytosis, a WBC > 100,000/mL, may also be seen on pre-
sentation. The incidence of hyperleukocytosis in AML ranges from 5% to
13%, and may lead to leukostasis.9 Patients with leukocytosis require
close monitoring and care to prevent and minimize complications.
Nurses can expect for these patients to receive aggressive intravenous
(IV) fluids, laboratory testing every 6 to 8 hours, and hydroxyurea to
help decrease theWBC count.10
In some cases leukocytosis can lead to leukostasis (a medical
emergency characterized by decreased tissue perfusion). Leukostasis
is caused by leukemic cells clumping in capillaries and is associated
with early mortality if not treated appropriately.11 Although any
organ system can be affected by leukostasis, the most common sitesare the central nervous system (CNS) and the lungs.9 CNS symptoms
can include confusion, dizziness, headache, tinnitus, vision changes,
delirium, coma, and ataxia; while respiratory symptoms can include
dyspnea, tachypnea, and hypoxia.9 A thorough physical nursing
assessment can quickly identify a patient who might be developing
leukostasis. Patients with leukostasis may require leukapheresis,
which is a process to rapidly remove leukocytes by mechanical sepa-
ration.10 Once a large-bore peripheral IV catheter or central line is
placed, apheresis should be performed. One apheresis session can
decrease circulating blasts by 20% to 50%.12
Diagnosis
The first step in the diagnosis of AML typically involves evaluating
the peripheral blood of patients for anemia, thrombocytopenia, and
leukopenia. Although leukocytosis is possible, leukopenia can also
occur.2 The diagnosis of leukemia then involves testing via bone mar-
row aspirate and biopsy, along with peripheral blood samples that
allow for flow cytometry, immunophenotyping, and morphologic
and genetic analysis.2,4,6,7 Bone marrow aspirate and biopsy results
often reveal a hypercellular marrow with a small number of normal
hematopoietic cells and a diffuse population of blasts.6 Flow cytome-
try is a test that uses a variety of dyes and chemical substances to
classify leukemia cells.6 Immunophenotyping is determined by the
pattern of surface proteins on the leukemic cells and allows for dis-
cerning between healthy cells and leukemia cells. Patterns of the cell
surface proteins and the level of differentiation are associated with
classification and diagnosis.13
A bone marrow biopsy or peripheral blood showing at least 20%
myeloblasts confirms the diagnosis of AML.1 Flow cytometry, cytoge-
netics, and molecular studies should be completed on the bone mar-
row aspirate and will aide in determining risk stratification.1
Antigens commonly expressed on AML blasts include CD13 and
CD33.14 Common cytogenetic abnormalities include t(15;17), t(8;21),
t(6;16), and inv(16).1 Chromosomal changes can be detected via
fluorescence in-situ hybridization (FISH) testing.6 Molecular analysis
may reveal abnormalities in NPM1, CEBP a, IDH1, IDH2, TP53, cKIT or
FLT3 ITD or TKD.4
The diagnostic workup of a patient with suspected AML should
also include a complete metabolic panel, liver function test, serum
lactic acid dehydrogenase, and uric acid. Patients without contraindi-
cations to hematopoietic cell transplant require human leukocyte
antigen typing. Other diagnostic testing, such as lumbar puncture or
computed tomography scans, may be needed based on patient symp-
toms and presentation.7 Treatment for AML often includes an anthra-
cycline, which will require an echocardiogram pretreatment.
Prognosis
There are both patient and disease-specific factors that are used
for risk stratification in AML. Patient-specific factors that predict
poorer performance include: age over 59 years; poor performance
status; and co-existing medical conditions.1 Disease-specific factors
that predict poorer performance include: high WBC at time of diag-
nosis; prior history of hematologic condition; cytogenetics; molecu-
lar markers; and disease related to prior chemotherapy, radiation, or
immunotherapy.1 Molecular markers have been validated to corre-
late with outcomes: NPM1, CEBP a, FLT3-ITD, cKIT, FLT3-TKD, IDH1,
IDH2, RUNX1, ASXL1, and TP53.14�16 See Table 1 for full cytogenetic
and molecular prognostic factors.
Treatment
The National Comprehensive Cancer Network recommends par-
ticipation in clinical trials, if available, for all patients diagnosed with
AML.4 Standard-of-care treatment for AML is determined by the
patient’s age, risk category, and baseline functional status.1 For adults
less than 60 years old with favorable or intermediate-risk AML, or
treatment-related AML, therapy often includes induction chemother-
apy with cytarabine plus an anthracycline (daunorubicin or idarubi-
cin). This regimen is typically referred to as 7+3.4 Patients with
treatment-related AML or with a prior history of myelodysplastic
syndrome can also receive a dual-drug liposomal encapsulation of
daunorubicin and cytarabine.4 More recent evidence points to an
added benefit in incorporating gemtuzumab ozogamicin in patients
with favorable-risk AML as well. Patients with a FLT3 mutation may
receive midostaurin as part of their 7+3 induction.17,18 A repeat bone
L.M. Blackburn et al. / Seminars in Oncology Nursing 35 (2019) 150950 3
marrow is typically done on day 14 to confirm a hypoplastic marrow,
and then again at the time of count recovery to assess the response to
the chemotherapy. Complete remission (CR) is defined as neutrophils
� 1,000/mL with platelets � 100,000/mL, and50% of waking hours
3 Capable of only limited self-care, confined to bed or chair more than
50% of waking hours
4 Completely disabled. Cannot carry on any self-care. Totally confined to
bed or chair
5 Dead
Data from Oken.19
Abbreviation: ECOG, Eastern Cooperative Oncology Group.
A key characteristic of APL is the presence of atypical promyelo-
cytes, both in the bone marrow and in the peripheral blood. The
promyelocytes show characteristic findings of bi-lobed nuclei and
azurophilic cytoplasmic granules. These granules can form elon-
gated bodies called Auer rods.28 This disease is distinguished from
other forms of AML by the cytogenetic translocation of the long
arms of chromosomes 15 and 17.29 One of the genes responsible,
the promyelocyte leukemia or PML gene, is on chromosome 15 and
is thought to be responsible for apoptosis and tumor suppression.
The other gene responsible, the retinoic acid receptor-alpha or
RARa, is on chromosome 17 and is mostly responsible for myeloid
differentiation. The translocation of genetic material that occurs
between these two chromosomes creates a fusion between parts of
the PML gene to parts of the RAR-a gene.28 This chromosomal trans-
location causes neither the PML nor the RAR-a protein to act in its
original capacity. Because of this morphology of chromosomes,
blood cells cannot differentiate past the promyelocyte phase, which
results in both the bone marrow and the peripheral blood being
filled with promyelocytes.
Clinical Presentation
The clinical presentation of APL, like that of AML, can be rather
nondescript, with many patients experiencing days to weeks of non-
specific symptoms followed by the occurrence of bleeding and
thrombosis.28 Symptoms can include infections, bruising, bleeding,
fevers, excessive sweating, fatigue, and tachycardia. Patients often
present through an emergency department. Misdiagnosis may occur
because of an underlying infectious process or bleeding. This can lead
to negative clinical outcomes because relatively quick treatment is
imperative. Advances in treatment options have increased the inci-
dence of both disease-free survival and CR, but there is still a high
mortality rate in the first month of diagnosis. This occurs because APL
is highly malignant in the initial stage when patients have severe coa-
gulopathies requiring emergent treatment.29
Diagnosis
Diagnostics for APL, as with AML, should include a bone marrow
aspirate and biopsy, complete blood count, metabolic panel, uric acid,
and lactate dehydrogenase. A screen for disseminated intravascular
coagulation (DIC) should be added for the diagnosis of APL. Prelimi-
nary testing of a complete blood count will show an increased WBC
and decreased red cells and platelets. The WBC differential may show
an increased percentage of promyelocytes. The bone marrow will be
screened for presence of the PML-RARa gene, reverse-transcription
polymerase chain reaction (or RT-PCR), but full results may take up
to a week. Cytogenetic testing identifies where genetic abnormalities
have occurred and FISH identifies the PML-RARa translocation. FISH
on peripheral blood for cytogenetic abnormalities can usually con-
firm the diagnosis in less than 24 hours. Patients with APL are divided
into three prognostic groups (see Table 3)4 based on their WBC and
platelet count, with patients at highest risk being those with a WBC
of > 10,000/mL at presentation (no matter their associated platelet
count).1,29
Table 3
APL risk stratification.
Risk status WBC Platelets
Low risk � 10,000/mL >40,000/mL
Intermediate risk � 10,000/mL 90% in patients newly
diagnosed with APL and 5-year disease-free survival rates have
improved to 74%.28,31 Patients who are high risk at diagnosis may
require both ATRA and anthracycline-based chemotherapy.4,27 For
these patients, idarubicin and ATRA are given until both hematologic
and molecular remissions occur, unless the patient is elderly or has
concomitant heart disease that would restrict the use of an anthracy-
cline.4,30 Alternative regimens now include gemtuzumab ozogamicin
in high-risk patients to reduce the risk of anthracycline-induced car-
diomyopathy and secondary malignancies years later.32 Patients with
APL require consolidation treatment to destroy any undetectable leu-
kemia cells that survive induction therapy. Consolidation consists of
additional ATO and ATRA for maintenance therapy, and possibly 6-
mercaptoprurine and methotrexate given for an additional 1 to
2 years, depending on the regimen used.25
Disseminated Intravascular Coagulation
Coagulopathic disorders are very common in patients with APL,
with almost 85% of patients experiencing them.28 Bleeding is fre-
quently the presenting symptom in patients with APL. Because these
complications are so frequently seen, it is imperative that clinicians
successfully identify potentially fatal conditions and react quickly
and succinctly. Researchers have found patients with APL to carry an
early death rate of 17%, with early death being defined as death
within 1 month of APL diagnosis.25,29 Other researchers have found
the early death rate to be somewhat higher, with a rate of 29%
reported within the first month of APL treatment.25,30 Greater than
60% of early death is caused by coagulopathy within the population
of patients with APL.31,33
Nursing interventions should include assessing the patient for air-
way, breathing, circulation, and level of consciousness changes, as
well as obvious signs of bleeding, petechiae, purpura, and other signs
of thrombotic events.10 Laboratory tests include complete blood
count, coagulation values (including fibrinogen, prothrombin time
(PT)/international normalized ratio (INR), partial thromboplastin
time (PTT), and D-dimer) should be obtained with assessments every
4 to 6 hours.1 Aggressive supportive treatment with blood products
is essential. This includes platelet transfusions to maintain platelet
levels > 30,000/mL, cryoprecipitate to maintain fibrinogen above 100
to 150 mg/dl, as well as fresh frozen plasma to correct abnormal PT/
INR and PTT values, plus red blood cells as necessary.27 Blood product
replacements are continued until the patient no longer shows signs
of coagulopathy.33 The early initiation of ATRA, even before a con-firmed diagnosis, should be anticipated by the nurse and may have a
great impact on the emergence of fatal bleeding disorders.28,33
Differentiation Syndrome
Differentiation syndrome (DS), also referred to as retinoic acid syn-
drome, is a potentially fatal development in patients with APL who
are undergoing induction therapy with ATRA or ATO.33 DS is charac-
terized by an elevated WBC, weight gain, unexplained fever, respira-
tory distress, interstitial pulmonary infiltrates, pulmonary edema,
pericardial effusion, unexplained hypotension, and acute renal fail-
ure.31 In a patient exhibiting one or more of these signs and symp-
toms, absent of other causes, DS should be considered and early
intervention should take place to avoid life-threatening complica-
tions.1 Diagnosis can be challenging because signs and symptoms can
be very nonspecific or parallel those of other complications, such as
septic shock.
About 50% of patients with APL treated with ATRA develop DS.31
Although variable, onset generally takes place between 2 and 21 days
into therapy. Patients receiving ATRA and ATO in combination have a
lower incidence of DS (16%) as opposed to patients who receive ATRA
or ATO alone (25% to 31%).31 Predictors of severe DS include serum
creatinine > 1.4 mg/dL and a WBC count > 5,000/mL at time of diag-
nosis. In comparison, a WBC count of 10,000/mL at time of diagnosis
predicts moderate DS.1
Treatment for APL causes differentiation and maturation of malig-
nant promyelocytes, and these maturing leukocytes invade tissues
and organs such as the lungs and kidneys.1 Production of inflamma-
tory chemokines and adhesion molecules promote local inflamma-
tion and leukocyte adhesion to alveolar epithelial cells.1 Oncology
nurses must be attentive to the early signs of DS, such as increased
work of breathing, cough, shortness of breath, decreased oxygen sat-
uration, hypotension, weight gain, fever, or decreased urinary output.
These symptoms can usually be correlated with a rise in the total
WBC during DS.33
Treatment with IV dexamethasone should begin as soon as the
initial signs and symptoms of DS are recognized and should be con-
tinued for at least 3 days or until the resolution of symptoms.31 Early
intervention is vital; corticosteroids started in the early stages of DS
better inhibit production of alveolar chemokines, lessening the
migration of differentiating APL cells to the alveolar space. Depending
on the degree of patient symptoms, ATRA and ATO might be stopped
and re-started with symptom resolution.31 ATRA and ATO may be
resumed at a full or reduced dose, but close monitoring for recurring
DS is critical.2 Because DS can be so severe, and yet is also very ste-
roid-responsive, some APL treatment regimens include the use of
prophylactic steroids upfront.31
Acute Lymphocytic Leukemia
Acute lymphocytic leukemia (ALL), also referred to as acute lym-
phoid leukemia and acute lymphoblastic leukemia, is a malignancy of
immature lymphocytes. Lymphocytes are a type of matureWBC that is
an integral part of the immune system. Lymphoblasts, a type of imma-
ture WBC, grow and mature into lymphocytes that are found in the
blood as well as the lymphatic system. Abnormal or malignant lym-
phoblasts are also called leukemic cells. These leukemic cells divide and
replicate, crowding out healthy cells in the bonemarrow.34 As ALL pro-
gresses, lymphoblasts spill out of the bone marrow and accumulate in
various areas, including the spleen, thymus, lymph nodes, liver, tes-
ticles of men, and the brain and spinal cord.34,35 Malignant lympho-
blasts do not go through the maturation process to become
lymphocytes, nor do they function as they should, and therefore the
body’s infection-fighting capabilities are compromised. These
L.M. Blackburn et al. / Seminars in Oncology Nursing 35 (2019) 150950 5
malignant cells block the production and development of healthy cells
and, unfortunately, grow and live longer than normal cells.34,36
At diagnosis, the ALL subtype is determined by which lymphocyte
is affected. There are three main types of lymphocytes: B lympho-
cytes (B cells) make antibodies; T lymphocytes (T cells) fight infec-
tions by activating the immune system, destroy infected and
diseased cells, and assist B cells;34�36 and natural killer cells fight
cancer cells and microbes.35
Incidence
It is estimated that in 2019, close to 6,000 people (children and
adults) in the United States were diagnosed with ALL.36 The incidence
in European countries is very similar to the rates noted in the US.7
with whites and Hispanics being more likely to develop ALL than
African Americans.35,36 ALL accounts for 60% to 74% of all leukemias
diagnosed in people under the age of 20,35 with children under
5 years of age having the highest risk.7,35 Approximately 20% of
patients diagnosed with ALL are over 55 years of age.37 In those diag-
nosed with ALL across all age groups, 75% to 88% will have the B-cell
subtype; 15% to 25% have the T-cell subtype; and the natural killer-
cell subtype of ALL is extremely rare.35
Etiology
The cause of ALL has yet to be determined, but there is thought
that the DNA changes found with ALL are not inherited from a par-
ent.36 However, genetic syndromes are linked to a higher risk.
Genetic abnormalities such as Down syndrome, Bloom syndrome,
ataxia teleangiectasia, Klinefelter syndrome, Fanconi anemia, and
Wiskott-Aldrich pose a higher risk of developing ALL.35 Genetic
changes in utero are the same genetic changes seen years after birth,
when a diagnosis of ALL has been confirmed.35
Clinical Presentation
Patients typically present to their primary care provider, local
urgent care, or emergency department with the same presenting
symptoms described for AML. Symptoms of anemia, thrombocytope-
nia, and ongoing infections are often what lead a person to seek care.
Some unique presenting symptoms of ALL are a direct result of the
subtype. Patients with B-cell ALL can present with CNS disease, while
lytic bone lesions, extramedullary disease, mediastinal mass and high
calcium levels may be noted more frequently in those with T-cell
ALL.2
Diagnosis
Diagnosis of ALL involves testing via bone marrow aspirate and
biopsy, along with peripheral blood samples that allow for flow
cytometry and immunophenotyping, morphologic and genetic analy-
sis as described.34�36,38 Bone marrow aspirate and biopsy results
often reveal a hypercellular marrow with a small number of normal
hematopoietic cells and a diffuse population of lymphoblasts. Flow
cytometry and immunophenotyping aides in determining if the ALL
is derived from the B-cell or T-cell lymphocyte.35,36,38
Patterns of the cell surface proteins and the level of differentiation
are associated with classification and diagnosis.37 B-cell ALL can be
further segmented into additional subtypes based on the differentia-
tion of the B cell, such as precursor B-cell ALL, intermediate or “com-
mon B-ALL”, and pre�B-cell, which is the most mature.2 Precursor B-
cell ALL cells most often express CD10, CD19, and CD34 proteins on
the cell surface, along with nuclear terminal deoxynucleotide trans-
ferase.39 Mature B-cell ALL, also called Burkitt cell leukemia,2 has a
male predominance and often a bulky extramedullary disease pre-
sentation.2,37 T-cell ALL cells typically express CD2, CD3, CD7, CD34,
and deoxynucleotide transferase.39 Wright-Giemsa�stained bone
marrow aspirate smears, hematoxylin and eosin-stained core biopsy
and clot sections are used for morphologic evaluation.34
Chromosomal changes in ALL often involve translocation of chro-
mosome 9 and 22, called Philadelphia chromosome positive (Ph-posi-
tive) disease.35,36,39 The incidence of this particular translocation,
which results in a BCR-ABL fusion gene, increases from 3% in children
up to more than 50% occurrence in adults over the age of 50.2 A trans-
location of chromosomes 12 and 22 with TEL-AML1 fusion gene is
frequently found in children.35 A newer subtype of ALL, Ph-like ALL,
exhibits geneexpression similar to Ph-positive ALL, but without the
translocation of chromosomes 9 and 22.
In addition to translocations, there are genetic changes that result
in an abnormal number of chromosomes. Instead of having the nor-
mal number of chromosomes (46), hyperdiploidy means there are
more than 50 chromosomes per leukemia cell and hypodiploidy indi-
cates there are less than 45 chromosomes per leukemia cell. Hyperdi-
ploidy is considered a favorable cytogenetic factor and hypodiploidy
is an adverse cytogenetic factor.2
Prognosis
Even though significant improvement in survival has been on the
rise over the past 2 decades for the adult population, there remains a
wide chasm between the overall survival of pediatric patients com-
pared with adults. The 5-year survival rate for people diagnosed with
ALL under the age of 20 is 89%, yet this same 5-year survival milestone
is only obtained by 35% of those who are 20 years of age and older.35
Having minimal residual disease detected after induction suggests a
poor prognosis.1 Patients diagnosed with Ph-like ALL have a very high
risk of relapse and the overall survival rate is poor.37 However, the
presence of the Ph chromosome allows for the use of novel targeted
therapies that may be changing the course of Ph+ ALL.40
Standard Treatment
CR is the treatment goal of induction therapy, and treatment
options are determined by risk stratification (Ph status and age).
Many other factors should also be considered, such as the subtype
and classification of ALL, the patient’s current health status, treat-
ment side effects, and the patient’s goals. Multi-agent systemic che-
motherapy regimens with drugs that cross the blood-brain barrier,
such as high-dose cytarabine and methotrexate, along with intrathe-
cal chemotherapy for CNS prophylaxis are standard treatments for
ALL.1 Systemic treatment regimens also include various combinations
of anthracyclines, vincristine, steroids, and cyclophosphamide.34
Philadelphia chromosome-positive disease is the largest subset of
patients with ALL in the older population.37 Ph-like ALL is treated
with the same regimens as Ph-positive ALL because even though the
Philadelphia chromosome is not present in the Ph-like subtype of
ALL, the genetic changes in the leukemia cells mimic those of the
Philadelphia chromosome.35 While Ph-positive ALL has often been
thought of as a high-risk disease, the addition of tyrosine kinase
inhibitors (TKIs) has improved remission rates.37 TKIs disrupt the sig-
naling process of the abnormal fusion gene (BCR-ABL) that promotes
leukemia cell growth.36 Imatinib, dasatinib, and nilotinib are a few
TKIs that target Ph-positive ALL.35 Targeted therapies include not
only TKIs, but drugs such as nelarabine that can be prescribed for T-
cell ALL.21 Other therapies that can be prescribed include: nelarabine
for T-cell ALL; ponatinib, which can target Ph-positive disease; rituxi-
mab, which can be added to chemotherapy to treat B-cell ALL if there
is significant expression of CD20; or blinatumuab and inotuzamab
ozogamicin.35 Blinatumomab directs the body’s own T cells to target
and destroy cells with the CD19 protein on the surface of B-cell lym-
phocytes. Blinatumomab is now approved by the US Food and Drug
Administration for the treatment of minimal residual disease after
6 L.M. Blackburn et al. / Seminars in Oncology Nursing 35 (2019) 150950
initial induction treatment in ALL, which is a paradigm-shifting
approach that may be improving our ability to achieve very deep
remissions and hopefully improve outcomes without the need for
riskier treatments like allogeneic stem cell transplantation.
Because of the higher remission rates in children than adults, adoles-
cent and young adult regimens routinely given to young children have
been adopted for the adult population in the 15- to 39-year-old age
range. Depending on the patient’s age at diagnosis, regimens for Ph-
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	Acute Leukemia: Diagnosis and Treatment
	Introduction
	Acute Myeloid Leukemia
	Etiology/incidence
	Clinical Presentation
	Diagnosis
	Prognosis
	Treatment
	Acute Promyelocytic Leukemia
	Clinical Presentation
	Diagnosis
	Treatment
	Disseminated Intravascular Coagulation
	Differentiation Syndrome
	Acute Lymphocytic Leukemia
	Incidence
	Etiology
	Clinical Presentation
	Diagnosis
	Prognosis
	Standard Treatment
	Oncologic Emergencies: The Nurses Role
	Tumor Lysis Syndrome
	Febrile Neutropenia and Sepsis
	Disseminated Intravascular Coagulation
	Conclusion
	References