716 Leukemia, Acute Myelogenous

C92.90Myeloid leukemia, unspecified, not PHYSICAL FINDINGS & CLINICAL

BASIC INFORMATION
DEFINITION
Acute myelogenous leukemia (AML) is a malig-
nancy of hematopoetic progenitor cells that
would normally give rise to mature myeloid
granulocytes. Strictly speaking, AML is a sub-
set of acute non-lymphocytic leukemia (ANLL),
broadly distinguishing these diseases from the
biologically distinct leukemias of lymphocytic ori-
gin and including leukemias involving the spec-
trum of myeloid stem cells, including precursors
of granulocytes, monocytes, erythrocytes and
megakaryocytes. Acute promyelocytic leukemia
is a distinct leukemia syndrome that is part of
the ANLL spectrum, but which has very different
treatment implications. ANLL is characterized by
maturation failure of myeloid progenitors, exces-
sive numbers of immature progenitors (blasts)
and various degrees of bone marrow failure
(neutropenia, thrombocytopenia, anemia).
SYNONYMS
Acute nonlymphocytic leukemia (ANLL)
Acute myeloid leukemia (AML)
ICD-10CM CODES
C92.60Acute myeloid leukemia with 11q23-
abnormality not having achieved
remission
C92.61Acute myeloid leukemia with 11q23-
abnormality in remission
C92.62Acute myeloid leukemia with 11q23-
abnormality in relapse
having achieved remission
C92.91Myeloid leukemia, unspecified in
remission
C92.92Myeloid leukemia, unspecified in
relapse
C92.A0Acute myeloid leukemia with
multilineage dysplasia, not having
achieved remission
C92.A1Acute myeloid leukemia with
multilineage dysplasia, in remission
C92.A2Acute myeloid leukemia with
multilineage dysplasia, in relapse
C92.Z0Other myeloid leukemia not having
achieved remission
C92.Z1Other myeloid leukemia, in remission
C92.Z2Other myeloid leukemia, in relapse
C92.00Acute myeloblastic leukemia, not
having achieved remission
C92.01Acute myeloblastic leukemia, in
remission
C92.02Acute myeloblastic leukemia, in
relapse
EPIDEMIOLOGY &
DEMOGRAPHICS
AML incidence rises with age:
 Incidence 20 to 55 years old: 1 to
3/100,000 persons/year.
 Incidence 65 to 80 years old: 11 to
20/100,000 persons/year.
Annual incidence is 4 cases/100,000 per-
sons/year.
Males slightly > females; European ancestry
slightly > African ancestry.
PRESENTATION
Symptoms/Exam Findings:
Complications of bone marrow failure:
Thrombocytopenia associated bleeding.
Fatigue and shortness of breath associ-
ated with anemia.
Infection associated with neutropenia.
Complications of leukocytosis (hyperleuko-
cytic leukemia, WBC > 100,000/mcl)
Retinal hemorrhage with visual symptoms.
Headache and intracranial bleeding.
 Respiratory symptoms from pulmonary
involvement.
Systemic symptoms
 Fatigue, fever (usually infectious, rarely
tumor), bone pain (more common in ALL).
Hemorrhagic complications of disseminated
intravascular coagulation (DIC), especially
with APML)
Physical exam will reflect consequences of
cytopenias (bruising from thrombocytopenia,
pallor from anemia). Enlarged lymph nodes
and enlarged liver and spleen are rare. Exam
is often normal.
Rarely disease will present as skin lesions
(leukemia cutis) or mass lesions (granulocytic
sarcoma).
Gum hypertrophy and organ/skin involvement
is more common in monocytic leukemia.
ETIOLOGY

Environmental/exposure related: Benzene
(best documented), organic solvents (includ-
ing gasoline), cigarettes smoking (20 pack

BOX 1L-1Stepwise Algorithm for Diagnosis and Classification of Acute Myelogenous Leukemia Using
Cytomorphology, Cytochemistry, Immunophenotyping, Cytogenetics, and Molecular Cytogenetics

The criteria are based on Wright-Giemsastained blood and
marrow smears and biopsy. The percentage of blast cells separates
acute myeloid leukemia (AML) from myelodysplastic syndrome
(MDS). The World Health Organization (WHO) classification defines
AML as greater than 20% blasts in the marrow or blood. The next
step is to define the blast population by immunophenotyping and/
or immunohistochemistry. The initial evaluation separates AML
from ALL. A history of exposure to prior cytotoxic chemotherapy or
agents associated with AML defines the leukemia as therapy-related
acute myeloid leukemia (t-AML). The WHO recognizes the unique clini-
cal and biologic features of the therapy-related leukemias (t-AML).
This subtype results from prior exposure to cytotoxic chemo-
therapy and/or radiation therapy. A majority of patients will have
clonal cytogenetic abnormalities and now account for more than
40% of all patients with AML. The WHO recognizes two types of
t-AML based on the type of prior exposure or treatment: alkylating
agentrelated AML and topoisomerase II inhibitorrelated AML. The
WHO classification defines major subgroups of AML that manifest
recurring cytogenetic abnormalities. As a group, these AMLs have
chromosomal translocations that result in the production of chime-
ric proteins, which are pivotal in the leukemogenic process. The
genetic abnormalities define a specific biology, clinical course, and
prognosis and therefore it is important to classify them separately.
In this group of patients, the diagnosis is defined by the cytoge-
netic abnormality independent of the percentage of blasts. There
are four recurrent translocations in this group. The diagnosis is
defined by the cytogenetic abnormalities and is not dependent on
the number of blasts: (a) AML with t(8;21)(q22;q22), (AML1/ETO)
(RUNX/CBFA2T1); (b) AML with abnormal bone marrow eosinophils
and inv16(p13;q22) or t(16;16)(p13;q22), (CBFB/MYH11); (c) acute
promyelocytic leukemia: AML with t(15;17)(q22;q21)(PML/RARA) or
t(11;17)(q23;q12) (PLZF/RARA) or t(5;17)(q23;q12)(NPM/RARA), or
t(11;17)(q13;q12) (NuMA/RARA); and (d) AML with 11q23 (MLL) ab-
normalities. If multilineage dysplasia is present, then the leukemia is
classified as acute leukemia with multilineage dysplasia.
AML with multilineage dysplasia is characterized by the presence of
20% or more blasts in the marrow and dysplasia in at least 50% of the
cells of at least two of the three main hemopoietic lines. The leukemia
may occur de novo or after a preceding myelodysplastic, myeloprolif-
erative, or overlap myelodysplastic/myeloproliferative syndrome unre-
lated to prior exposure to chemotherapy. If such a syndrome preceded
the development of acute leukemia, the AML is best designated as
AML evolving from a myelodysplastic syndrome. When a leukemia
fails to satisfy the cytogenetic, morphologic, or clinical criteria for the
newly defined subgroups, it is classified as AML not otherwise cat-
egorized. The not otherwise categorized designation essentially applies
the original FAB classification with some modifications, namely, acute
promyelocytic leukemia (M3) is no longer included; a pure erythroleu-
kemia has been distinguished from erythroleukemia, acute erythroid/
myeloid type; and acute basophilic leukemia (very rare) has been
added, as is a rare entity termed acute panmyelosis with myelofibrosis
and the solid tumor myeloid sarcoma.

CD, Cluster designation; MPO, myeloperoxidase; NEC, nonerythroid cells; NSE, nonspecific esterase; PAS, periodic acidSchiff; SBB, Sudan black B; TdT, terminal deoxynucleo-
tidyl transferase; TNC, total nucleated cells.
From Hoffman R etal: Hematology, basic principles and practice, ed 5, Philadelphia, 2009, Churchill Livingstone.

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year 1.34 relative risk), obesity, best docu-

mented in women.
Hereditary disorders: Numerous, includ-
ing Fanconi anemia, Bloom syndrome,
Schwachman Diamond syndrome, Diamond
Blackfan anemia, among others.
Therapy related:
Alkylator (e.g. melphalan, busulfan, cispla-
tin) related: typical latency 5 to 7 years,
associated with chromosome 5 and 7
abnormalities..
Topoisomerase II inhibitor (e.g. etoposide,
doxorubicin): typical latency 1-3 years,
associated with 11q23 (mixed lineage
leukemia (MLL) gene) rearrangements.
Radiation exposures (therapeutic generally
low risk), occupational.
Antecedent hematologic disorders:
Myelodysplasia, myeloproliferative disorders,
aplastic anemia.
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
Disorders that can present with circulating
blasts or cells with blast like appearance:
 Acute myeloid leukemia/acute lympho-
cytic leukemia.
 Myelodysplasia (up to 20% circulating
blasts, if 20% = AML).
Primary myelofibrosis.
Chronic myeloid leukemia
Blastoid variant of mantle cell lymphoma.
Prolymphocytic leukemia
Blastic plasmacytoid dendritic cell neo-
plasm.
Atypical lymphocytes of Epstein Barr virus
and other viral syndromes.
LABORATORY TESTS
Complete blood counts and blood smear
evaluation. Note that morphologic evaluation
of blasts may suggest myeloid or lymphoid
origin, but flow cytometry or cytochemistries
(often faster) are needed to confirm. Auer
rods equal myeloid origin.
LDH is commonly elevated. Other biochem-
istries to assess organ function (creatinine,
liver enzymes) and spontaneous tumor lysis
syndrome (uric acid, potassium phosphate,
calcium).
Coagulation studies to assess DIC (always
present in APML, but can be present in
all forms of acute leukemia, especially acute
monocytic leukemia.
HLA typing for possible bone marrow trans-
plant and platelet support.
Cytochemical stains
 Myeloperoxidase can be performed in
minutes, + in myeloid origin leukemia.
 Alpha naphthyl acetate esterase (non-
specific esterase) stains mainly mono-
cytic cells.
Flow cytometry on blood and/or bone marrow
(see Table 1L-8)
Cytogenetic studies, ideally on bone mar-
row, but can be done on peripheral blood.
Fluorescence in situ hybridization (FISH) is
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Leukemia, Acute Myelogenous
Table 1L-8 Flow Cytometry Markers Used For Diagnosis of ANLL
Precursor stage CD34, CD38, CD117, CD133, HLA-DR
Granulocytic (myeloid) markers CD13, CD15 CD16, CD33, CD65, cytoplasmic myeloperoxidase
Monocytic markers CD11c, CD14, CD64, CD4, CD11b, CD36, NG2 homologue
Megakaryocytic markers CD41 (glycoprotein IIb/IIIa), CD61 (glycoprotein IIIa), CD42 glycoprotein
1b
Erythroid markers CD235 (glycophorin A)
Adapted from Doehner H etal, Diagnosis and management of acute myeloid leukemia in adults, recommendations from an inter-
national expert panel, on behalf of the European LeukemiaNet, Blood 115: 453-474, 2010.
often used as an adjunct to conventional
chromosome analysis.

Molecular studies to further stratify risk
groups and prognosis (see Table 1L-9).

Formal diagnosis of acute nonlympho-
cytic leukemia is established if the marrow
blast percentage is 20%, unless t(8;21),
inv(16), t(16;16) or t(15;17) are present, in
which case the percentage of blasts may
be lower.
Myeloperoxidase (MPO) staining of 3%
of blasts establishes myeloid lineage, but
MPO may be negative in some AML cases
diagnosed by flow cytometry.
Specific criteria exist for diagnosing other
forms of ANLL, mainly to distinguish from
myelodysplasia. The WHO AML classifica-
tion is outlined in Table 1L-10.
Cytogenetic risk categories in AML are
described in Table 1L-11. Bone marrow
findings are described in Fig. E1L-9.
IMAGING STUDIES
Imaging studies are typically directed to
evaluating specific complaints.
Echocardiogram or MUGA is usually needed
to verify adequate cardiac function to tol-
erate anthracycline (usually daunorubicin)
therapy, with left ventricular ejection frac-
tion (LVEF) of > 50% typically considered
acceptable.
TREATMENT
ACUTE GENERAL Rx
Therapy of AML typically has three compo-
nents:
 Immediate therapy to correct metabolic,
infectious, or hyperleukocytic emergencies
(if needed).
Induction therapy, which is therapy of active
disease intended to obtain remission and
restore normal bone marrow function.
Remission is defined as blasts <5% in the
bone marrow, absolute neutrophils (ANC) of
> 1000/mcl, platelets > 100,000/mcl and
transfusion independence.
Consolidation therapy, typically some form
of intensive chemotherapy or stem cell
transplant therapy intended to prevent
relapse.
Hyperleukocytic symptoms are most typi-
cally seen with WBC > 100,000/mcl.
 Leukapheresis requires catheter place-
ment and pheresis, but spares tumor lysis.
717
L
and Disorders
Diseases
 Rapid cytoreduction with chemotherapy
(cytarabine, hydroxyurea 3 grams orally)
often adequate and easier, but risks of
acute tumor lysis. Optimal management is
therefore individualized.
 Tumor lysis syndrome (TLS) is associ-
ated with rise in uric acid, potassium and I
phosphate (with reciprocal fall in calcium)
levels as well as renal failure.
Mainstay of therapy is vigorous hydration
possibly with furosemide to maintain urine
output > 100 ml/m2/hour. Urinary alkalini-
zation is controversial, usually not helpful.
Allopurinol up to 600 mg PO or IV, adjusted
for renal failure) for hyperuricemia.
Rasburicase (0.05-0.2 mg/kg) lowers uric
acid rapidly (hours) with single dose in TLS
emergency; avoid in patients with G6PD
deficiency.
Induction chemotherapy typically consists
of daunorubicin 60 or 90 mg/m2 IV for 3
days and cytarabine (Ara-C) 100 or 200
mg/m2/day as continuous infusion for 7
days (7+3).
Success rates are 60% to 80% and have
been better in recent trials. Other agents
used have included etoposide, idarubicin,
and fludarabine, among others. Bone mar-
row examination is commonly performed at
day 14 to assess adequacy of response with
additional therapy given for large amounts of
persisting disease.
Consolidation therapy is controversial.
Cytarabine 3 gm/m2 for six doses was used
for many years, but intermediate doses
(1000-1500 mg/m2) for six doses appears
equally effective and less toxic. Doses above
1000 mg/m2 are poorly tolerated in patients
over 60 yr because of cerebellar toxicity.
 For favorable risk disease, consolida-
tion with chemotherapy alone with 2 to
4 cycles of intermediate/high dose cyta-
rabine is typically given with long term
survival of 60% to 70%.
For intermediate risk and unfavorable risk
disease, first remission allogeneic stem cell-
marrow transplant is often recommended if a
donor is available. If not, chemotherapy con-
solidation chemotherapy is offered, although
the optimal therapy and schedule, especially
for unfavorable disease, is uncertain.
 The role of autologous stem cell mar-
row transplant is controversial, with some
evidence of a decrease in relapse rates
after chemotherapy, but no clear benefit in
overall survival.
718 Leukemia, Acute Myelogenous
Treatment of older patients (>60 yr) is prob-
Table 1L-9 Significance of Molecular Abnormalities in Cytogenetically
lematic, with cure rates of 10% to 15%. Older
Normal Patients With AML patients do worse because they are more
Molecular profile Patients 4 year overall survival likely to have high risk features and less
likely to tolerate therapy. Options for these
Mutant CEBPA 67 62% patients include:
Mutant NPM, without FLT-3 ITD 150 60% Standard induction therapy is reasonable
FLT-3 ITD present 164 24% for patients likely to tolerate it. Even in the
FLT-3 ITD absent, wild type NPM, wild type 69 33% absence of cure, quality of life is excellent
CEBPA (triple negative leukemia) in remission. Patients over 80 yr do not
usually benefit, although this has been
CEBPA, CCAAT/enhancer binding protein gene; FLT-3 ITD, fms-related tyrosine kinase gene internal tandem duplication; NPM, reconsidered recently. Some form of con-
nucleophosmin gene.
Improved prognosis in patients with CEBPA mutations is limited to patients who lack FLT-3 ITD and have double mutations. CEBPA
solidation is usually given, with presumed
mutations are seen in approximately 6% to 10% of AML cases, NPM mutations in 25% to 35% (more common in cytogenetically greater benefit in favorable risk disease.
normal cases) and FLT-3 ITD in approximately 20% to 30% of cases. The optimal regimen is not known.
Data from Schlenk RF, etal: N Engl J Med 358: 1909-18, 2008, and Green CL, etal: J Clin Oncol 28: 2739-47, 2010.  Hypomethylating agentsdecitabine and
azacytidinemay be considered in patients
unlikely to tolerate induction therapy, espe-
TABLE 1L-10 Classification of Acute Myeloid Leukemia According to the cially in the setting of low blast count (20%-
Revised World Health Organization Classification (2008) 30% bone marrow blasts) leukemia.
 Low dose cytarabine (20 mg/m2 twice
Category Subtype/Definition daily or 40 mg/m2 daily for 10 days sub-
cutaneously) has shown survival benefit
AML with recurrent cytogenetic abnormalities t(8;21)(q22;q22); RUNX1-RUNX1T1* over hydroxyurea in low/intermediate risk
inv(16)(p13.1q22); CBFB-MYH11*
patients.
t(16;16)(p13.1q22); CBFB-MYH11*
t(15;17)(q22;q12); PML-RARA*  Oral hydroxyurea dosed to counts and
t(9;11)(p22;q23); MLLT3-MLL cytopenias.
t(6;9)(p23;q34); DEK-Nup214 Best supportive care.
inv(3)(q21q26.2); RPN1-EVI1  Reduced intensity allogeneic stem cell
t(3;3)(q21;q26.2); RPN1-EVI1 transplant has yielded cure rates of 20%
t(1;22)(p13q13); RBM15-MKL1 to 40% of highly selected patients, typically
AML with MDS-related changes Morphologic features of MDS, or ages 60 to 75, and is an option for some.
Prior history of MDS or MDS/MPN, or Acute Promyelocytic Leukemia (APML)
MDS-related karyotype, and APML is a distinct leukemia syndrome with
None of the recurrent genetic abnormalities above very different treatment implications. Cure
Therapy-related myeloid neoplasms Late complications of cytotoxic chemotherapy (alkylating rates greater than 95% have been seen in
agents, topoisomerase II inhibitors) and/or ionizing current protocols in the absence of high risk
radiation therapy
features. It is associated with t(15;17), which
AML, not otherwise specified AML with minimal differentiation translocates the PML gene to retinoic acid
AML without maturation
receptor (PML-RARa). Uncommon variants
AML with maturation
Acute myelomonocytic leukemia are t(11;17) and t(5;17).
Acute monoblastic/monocytic leukemia Risk groups in APML receiving anthracy-
Acute erythroid leukemia cline and retinoic acid therapy:
Acute megakaryoblastic leukemia
Acute basophilic leukemia High risk: WBC >10,000/mcl
Acute panmyelosis with myelofibrosis Intermediate WBC 10,000/mcl,
Myeloid sarcoma risk: platelets 40,000/
Myeloid proliferations related to Down syn- Transient abnormal myelopoiesis mcl.
drome Myeloid leukemia associated with Down syndrome Low Risk: WBC 10,000/mcl,
Blastic plasmacytoid dendritic cell neoplasm platelets > 40,000/
Acute leukemia of ambiguous lineage Acute undifferentiated leukemia mcl.
Mixed-phenotype acute leukemia with t(9;22)
(q34;q11.2); BCR-ABL1  Patients in low and intermediate risk
t(v;11q23); MLL rearranged groups (WBC 10,000) had a two year
Mixed-phenotype acute leukemia, B/myeloid, NOS event free survival of 97% using all tran-
Mixed-phenotype acute leukemia, T/myeloid, NOS sretinoic acid (ATRA) and arsenic trioxide
Provisional entities AML with mutated NPM1 (AsO3) therapy in a recent trial.
AML with mutated CEBPA Patients in the high risk group had approx-
NK-cell lymphoblastic leukemia/lymphoma imately 75% 5 year survival using anthra-
cycline (idarubicin) and ATRA therapy.
AML, Acute myeloid leukemia; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; NK, natural killer.
*Diagnosis of AML regardless of percentage of blasts. APML is a medical emergency because of the
Excluded are patients with AML who have transformed from MPN. high risk of bleeding complications.
From Hoffman R: Hematology, basic principles and practice, 6th ed, Philadelphia, 2013, Saunders. All patients with APML have DIC, caused
by overexpression of annexin II, (which
Allogeneic stem cell transplant is offered lymphocyte infusions, adjustment of increases generation of plasmin, degrad-
to patients with relapsed disease if a sec- immune suppression to increase the graft ing fibrin), elastases (which degrade
ond remission can be obtained. vs. leukemia effect, and chemotherapy. fibrinogen and fibrinolytic inhibitors), and
Relapses after bone marrow transplant In general, outcomes are poor with post- increased endothelial tissue plasminogen
can sometimes be managed with donor transplant relapses. activator release.

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 Leukemia, Acute Myelogenous 719

daunorubicin) to lower WBC and decrease

Table 1L-11 European LeukemiaNet Defined Cytogenetic and Molecular
Abnormalities Relevant to Prognosis in AML
risk of differentiation syndrome
Maintenance therapy for 2 years is given L
Favorable t(8;21)(q22;q22)*
in some APML protocols
inv (16)(p13.1;q22) or t(16;16) (p13.1;q22) * Differentiation syndrome (DS) is a potentially
Normal karyotype with mutated NPM1 and absent FLT-3 ITD fatal complication of therapy with retinoic
Normal karyotype and mutated CEBPA acid and arsenic trioxide. It is associated
Intermediate-1 Normal karyotype and mutated NPM1 and FLT3-ITD with fever, interstitial pulmonary infiltrates,
Normal karyotype with wild type NPM1 and FLT3-ITD peripheral edema, pleural and pericardial
Normal karyotype without FLT3-ITD effusions and renal failure; it is commonly
Intermediate-2 t(9;11)(p22;q23) associated with rising WBC seen in patients
Cytogenetic abnormalities not classified as favorable or adverse on differentiation therapy.
Therapy for suspected differentiation syn-

and Disorders
Diseases
Adverse Complex (3 or more abnormalities, unless associated with a known favorable
abnormality), drome is dexamethasone 10 mg/m2 every
inv(3)(q21;q26.2) or t(3;3)(q21;q26.2); 12 hr. Stopping retinoic acid and arsenic
t(6;9)(p23;q34) is appropriate for inadequate response to
t(variable;11)(variable;q23) (MLL gene rearrangement), dexamethasone.
-5 or del (5q);  Prophylaxis for differentiation syndrome
-7;
abnormal (17p)
with dexamethasone 2.5 mg/m2 every 12
hr has been suggested for WBC >5000 or I
*AML associated with t(8;21)(q22;q22), inv (16)(p13.1;q22) or t(16;16) (p13.1;q22) are referred to core binding factor (CBF) leuke- creatinine > 1.4 mg/dl.
mias. CBF is a modulator of DNA transcription that is affected by these mutations. Favorable risk groups have had 5 year surviv-
als of about 60%, intermediate risk of approximately 25% to 30% and unfavorable risk of less than 5% in clinical trials from
the 1990s. PEARLS &
Adapted from Doehner H etal, Diagnosis and management of acute myeloid leukemia in adults, recommendations from an inter-
national expert panel, on behalf of the European LeukemiaNet., Blood 115: 453-474, 2010. CONSIDERATIONS
The diagnosis of acute myeloid leukemia or
Early death due to hemorrhage is seen Diagnosis of APML variants is often, but not always, a medical
in 5% to 17% of newly diagnosed APML Rapid diagnosis is essential due to treatment emergency requiring rapid clinical and labo-
patients, usually intracranial or pulmo- implications, Tests commonly available in 24 ratory assessment by appropriate expertise.
nary. Risk factors include elevated WBC, to 48 hours depending on local availability APML is a distinct clinical entity with a high cure
increased age, and elevated creatinine. Polymerase chain reaction for PML/RARa rate with current protocols, but requires inten-
Retinoic acid rapidly stabilizes the coagu- FISH for t(15;17) or variants sive supportive care at the time of diagnosis.
lopathy of APML; consideration should Flow cytometry is typically distinct with
be given to starting this immediately for lack of HLA-DR and CD34; CD13, CD33
suspected cases. and CD64 are usually positive SUGGESTED READINGS
Cryoprecipitate (usual dose 10 bags) Therapy of APML Available at www.expertconsult.com
to raise the fibrinogen level to 150 mg/ Emergency measures to stabilize coagu-
dl and platelet transfusion to raise the lapathy as outlined previously RELATED CONTENT
count to >50,000//mcl should be given Patients with WBC 10,000 (low/intermedi- Acute Myelogenous Leukemia (Patient
as needed. ate risk) are treated with retinoic acid and Information)
Unfractionated heparin may paradoxically arsenic trioxide (differentiation therapy) AUTHOR: PETER RINTELS, M.D.
stop bleeding in APML by inhibiting DIC,  Optimal therapy of higher risk patients
but is rarely used in the retinoic acid treat- is less well defined and may include
ment era. anthracyclines (commonly idarubicin, also

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Leukemia, Acute Myelogenous 719.e1

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Doehner H, etal.: Diagnosis and management of acute myeloid leukemia in
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Lo-Coco F, etal.: Retinoic acid and arsenic trioxide for acute promyelocytic leu-
kemia, N Engl J Med 369(2):111121, 2013.
Sanz MA, Montesinos P: How we prevent and treat differentiation syndrome in
patients with acute promyelocytic leukemia, Blood 123(18):27772782, 2014.
Sanz MA, Tallman MS, Lo-Coco F: Tricks of the trade for the appropriate manage-
ment of newly diagnosed acute promyelocytic leukemia, Blood 105(8):3019
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Schlenk RF, etal.: Mutations and treatment outcome in cytogenetically normal
acute myeloid leukemia, N Engl J Med 358(18):19091918, 2008.
Strom SS, etal.: De Novo acute myeloid leukemia risk factors: A Texas case-
control study, Cancer 118:45894596, 2012.
Vardiman JW, etal.: The 2008 revision of the World Health Organization (WHO)
classification of myeloid neoplasms and acute leukemia: rationale and impor-
tant changes, Blood 114(5):937951, 2008.
Zuckerman T, etal.: How I treat hematologic emergencies in adults with acute
leukemia, Blood 120(10):19932002, 2012.
Walter MJ, etal.: Clonal architecture of secondary acute myeloid leukemia, N Engl
J Med 366:10901098, 2012.

A C
FIGURE E1L-9 Acute myeloid leukemia with t(8;21)(q22;q22), (AML/ETO). A, Low-power, Wright-
stained bone marrow aspirate smear showing increased blasts associated with differentiating myeloid cells. B,
Details illustrating some of the features associated with the leukemia. They include blasts with long thin Auer
rods (top left), immature cells with abnormal eosinophilic globules (top and bottom, second from left), abnormal
salmon-colored granulation in the maturing cells, sometimes associated with a basophilic periphery (top and
bottom, fourth from left), and slightly abnormal features in the mature neutrophils (far right). PseudoChdiak-
Higashi granules were not seen in this case. C, Biopsy shows the significant degree of maturation that is
sometimes seen. In some cases the blast count is less than 20%, but the diagnosis of acute myeloid leukemia
still can be made with the cytogenetic finding of t(8;21). (From Hoffman R etal: Hematology, basic principles
and practice, ed 5, Philadelphia, 2009, Churchill Livingstone.)

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