A Patient with Pancytopenia

Peter W. Marks, MD
Yale University School of Medicine, New Haven, CT

Copyright of the American Society of Hematology, 2012. ISSN: 1931-6860.

Section I: History

A 34-year-old woman is seen by her dentist for bleeding from her gums. The bleeding started on
the day prior to evaluation and seems to be getting steadily worse with time.

After briefly evaluating the patient and noting diffuse bleeding from the mucosal surfaces around
multiple teeth, the dentist refers her for further evaluation to the emergency department at a
nearby hospital where you are working.

What further information should you request regarding this patient’s history?

Have you ever had a similar episode in the past?

Good choice!
A personal history of a similar episode or episodes in the past, occurring spontaneously or with trauma
or surgery, might indicate the presence of a hematologic disorder associated with mucosal bleeding,
such as von Willebrand disease or a platelet function defect. Non-hematologic causes of gum bleeding
include periodontal disease, the presence of which a dentist would identify.
Is there any family history of a bleeding disorder?
Good choice!
Family history is an important component when evaluating a patient for the possibility of a bleeding
disorder, as von Willebrand disease and platelet function defects are often inherited.
Are you taking any prescribed or over-the-counter medications?
Good choice!
Multiple medications can affect the hemostatic system. Although non-steroidal anti-inflammatory drugs
(NSAIDs) or aspirin alone (reversible and irreversible cyclooxygenase inhibitors, respectively) would be
unlikely to cause such significant bleeding, many other medications can affect the hemostatic system,
including warfarin, heparins, selective-serotonin reuptake inhibitors (SSRI antidepressants) and herbal
supplements.
Do you smoke cigarettes or drink alcohol?
Good choice!
Although cigarette smoking may be associated with injury to the oral mucosa and staining of the teeth,
it is not associated with a bleeding disorder. However, heavy alcohol use may be associated with the
development of thrombocytopenia on the basis of hypersplenism and bone marrow suppression, and a
coagulopathy is associated with the development of liver failure from cirrhosis associated with chronic
alcohol use.
Do you have any bruises or other areas of bleeding?
Good choice!
The presence of one bleeding symptom should lead to a search for other bleeding complications.
Petechiae (small areas of bleeding under the skin) and ecchymoses (bruises) might be observed. Other
mucosal bleeding such as epistaxis (bleeding from the nose) or menorrhagia (heavy vaginal bleeding)
might occur, as well as gastrointestinal bleeding, as evidenced by bright red blood or melena (dark or
black tarry stools).
Is anyone else in your family ill?
Try another choice.
Although conceivably, bleeding gums could be the end result of a communicable or acquired illness (for
example, hemorrhagic dengue or hemolytic-uremic syndrome), this likelihood, in the absence of other
associated symptoms, is small.
Do you have any pets?
Try another choice.
A zoonotic infection is unlikely to be the cause of this patient’s gingival bleeding.
Section I: History

The patient notes that she has never had an episode of anything similar in the past. Her past
medical history is remarkable only for a tonsillectomy at age 11 that was entirely uncomplicated.
There is no family history of a bleeding disorder. She takes no medication regularly, but on
occasion takes acetaminophen for headaches. She does not smoke or drink alcohol.

On a review of systems, you discover that over the past month she has been feeling gradually
more fatigued, which she attributes to working overtime at her job as an administrative assistant.
She notes no fevers or chills but does say that she may have lost a few pounds unintentionally
due to decreased appetite. She notes that on her way to the emergency department, she noted
some small bruises on her forearms and thighs and that her ankles and feet seem to have
numerous small red dots on them. She denies any chest pain, shortness of breath, abdominal
pain, edema, headaches, dizziness, or other neurologic symptoms.

After obtaining this information, you move on to perform a physical examination on the
patient.

PERTINENT PHYSICAL FINDINGS

General Pale appearing woman in no acute distress. T 98.9°F, P 105, BP 94/64, RR 16.
Notable for several 2-3 cm ecchymoses on the forearms and thighs bilaterally; in
Skin
addition, there is a petechial rash over the ankles and feet bilaterally.
The oropharynx is notable for a small amount of fresh blood at the gum line around
HEENT
the base of multiple upper and lower incisors and molars.
Normal S1, S2, regular, with a grade I/VI systolic murmur appreciated at the left
CV
sternal border.
Pulm Unlabored respiration, clear to auscultation and percussion bilaterally.
Abd Soft, non-tender, non-distended, without organomegaly or mass.
Warm, well perfused, no edema, but with the ecchymoses and petechiae noted
Extr
above.
Neuro Alert and oriented to person, place, and time. No motor or sensory defects.
What additional information would you request at this time?

Laboratory Data
correct
Radiologic Studies
Incorrect.
Not indicated at this time
What laboratory data should you request initially? Select all that apply.

CBC with differential

Good choice!
The recent history of fatigue and the finding of petechiae suggest the possibility of anemia and
thrombocytopenia, respectively. The complete blood count will provide a wealth of information in this
regard that may help to indicate a diagnosis.
Peripheral blood smear
Good choice!
In a case in which anemia and/or thrombocytopenia is suspected, review of the peripheral blood smear
will provide important diagnostic clues to the underlying etiology and may even provide a specific
diagnosis.
Prothrombin time (PT)
Good choice!
This patient has signs of bleeding, with petechiae and ecchymoses. Evaluation for a possible coagulation
abnormality that might be present, such as disseminated intravascular coagulation, is indicated.
Activated Partial Thromboplastin time (aPTT)
Good choice!
This patient has signs of bleeding, with petechiae and ecchymoses. Evaluation for a possible coagulation
abnormality that might be present, such as disseminated intravascular coagulation, is indicated.
Serum creatinine
Good choice.
This patient appears to have a systemic illness, and with the finding of petechiae, may have
thrombocytopenia. Knowledge of the serum creatinine will be helpful in developing a differential
diagnosis. For example, the serum creatinine may be elevated in thrombotic thrombocytopenic purpura
or hemolytic uremic syndrome.
Liver function tests
Good choice.
Thrombocytopenia can be associated with liver disease due to a variety of causes, so evaluation of the
liver function tests is warranted.

Section III: Laboratory Data

On Routine
  Office Visit Today Normal Range
3 Months Ago

CBC
  WBC count 7,800/µL 2,300/µL 4,100-10,900/µL

  Differential      

    Neutrophils 65% 16% 38-80%

    Lymphocytes 29% 37% 30-50%

    Monocytes 6% 18% 2-12%

    Blasts --- 29% 0%

  Hemoglobin 13 g/dL 8 g/dL 13-15 g/dL

  Hematocrit 41% 26% 39-45%

  MCV 89 fL 87 fL 80-100 fL

  Platelets 225,000/µL 7,000/µL 140,000-440,000/µL

Coagulation Studies

  PT --- 16 seconds 12-14 seconds

  aPTT --- 41 seconds 23-31 seconds

Serum creatinine 0.6 mg/dL 1.1 mg/dL 0.5-1.2 mg/dL

Liver Chemistries

  ALT --- 45 U/L 7-56 U/L

  AST --- 31 U/L 5-35 U/L

  Alkaline phosphatase --- 131 U/L 20-140 U/L

  Total protein --- 7.3 g/dL 6.3-8.2 g/dL

  Albumin --- 3.7 g/dL 3.5-5 g/dL

  Total bilirubin --- 1.6 mg/dL <1.20 mg/dL

  Direct bilirubin --- 0.2 mg/dL <0.20 mg/dL

Section III: Laboratory Data

Are there further laboratory data, radiographic studies, or diagnostic procedures that you
would wish to request at this time?

Fibrinogen level
Good choice!
Fibrinogen levels can be decreased in disseminated intravascular coagulation (DIC), a consumptive
coagulopathy that can cause increases in the PT and/or aPTT. Depletion of fibrinogen alone could
potentially explain an increase in both the PT and aPTT. Since formation of fibrin from fibrinogen is the
final step that leads to the formation of clot, which is the endpoint in both the PT and aPTT assays,
depletion of fibrinogen to levels significantly below normal (<100 mg/mL) can lead to increases in both
values. Alternatively, both tests can be elevated because of a deficiency in the so-called common
pathway factors (II, V, X) or through depletion of multiple factors of the clotting system in DIC.

LDH

Good choice!
The LDH may be elevated in a number of different conditions, including microangiopathic hemolytic
anemias such as disseminated intravascular coagulation (DIC); hematologic malignancies such as
leukemia or lymphoma; and in other conditions that lead to intramedullary (within the bone marrow)
destruction of blood cell precursors, such as folate or vitamin B 12 deficiency.

Uric acid

Good choice!
In any condition in which there is rapid cell turnover associated with the death of cells and metabolism
of DNA, uric acid, a breakdown product of purine nucleotide metabolism, may build up in the
bloodstream. Uric acid is poorly soluble and tends to become insoluble in the kidney at high
concentration.

CT scan of the chest, abdomen, and pelvis

Incorrect.
There are no historical features, physical findings, or laboratory abnormalities that suggest that a CT
scan of the chest, abdomen, and pelvis is needed at this time. Although acute myeloid leukemia can
sometimes be associated with the development of tumor-like masses of leukemia cells (chloromas),
there is no evidence of this at presentation on this patient’s physical examination.

Lumbar puncture

Incorrect.
This patient is having no neurologic symptoms. In addition, the presence of thrombocytopenia and a
coagulopathy are a contraindication to this procedure at this time, unless they are corrected by blood
product administration. There is also a theoretical concern that a lumbar puncture performed when
there are circulating blasts could introduce these into the cerebrospinal fluid (CSF). That being said, if
there were neurologic symptoms or signs, a lumbar puncture could be performed after correction of the
coagulopathy.

Bone marrow aspirate and biopsy

Good choice!
The diagnostic procedure of choice for the underlying disorder is a bone marrow aspirate and
biopsy. The bone marrow aspirate is generally performed from the posterior iliac crest region.
A bone marrow aspirate allows evaluation of morphology, histochemistry, flow cytometry,
cytogenetics, and molecular diagnostic studies. The biopsy allows determination of the
percentage of cellularity involved with the leukemia and facilitates immunohistochemical
staining in order to further characterize the blasts present.
To see how a bone marrow aspirate and biopsy are performed, refer to the following video:
Malempati S, Joshi S, Lai S, et al. Bone marrow aspiration and biopsy. New Engl J Med.
2009;361:e28.
The bone marrow aspirate and biopsy are sent to the laboratory for processing. Results will be
available according to the following very approximate timeline:

Bone marrow aspirate for morphologic review 1 hour

Histochemical stains on bone marrow aspirate 3 hours
Flow cytometry on bone marrow aspirate 6 hours
Molecular diagnostic studies 6 hours
Bone marrow biopsy for morphologic review 24 hours
Fluorescence in situ hybridization (FISH) for translocations 24 hours
Conventional cytogenetic analysis 96 hours

Section IV: Differential Diagnosis

While the bone marrow aspirate and biopsy are being processed, what is the most likely
diagnosis for this patient based upon all of the data provided?

Aplastic anemia

Try another choice.

Although aplastic anemia is associated with pancytopenia, unless a complicating factor such as severe
liver disease or sepsis is present, it is not associated with a coagulopathy. This patient has no evidence of
significant liver disease or sepsis. In addition, there are many blasts on peripheral blood smear. These
would not be seen in the peripheral blood of a patient with aplastic anemia.

Paroxysmal nocturnal hemoglobinuria

Try another choice.

Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder in which the PIGA gene
encoding phosphatidylinositol glycan anchor biosynthesis is mutated, leading to the loss of a class of
membrane proteins that is anchored by this linkage. This is associated with pancytopenia and
thrombotic complications but is not associated with a significant coagulopathy involving elevation of the
PT and/or aPTT.

Sepsis syndrome

Try another choice.

Sepsis may cause pancytopenia related to myelosuppression and may also be associated with the
development of disseminated intravascular coagulation. However, this patient has no other symptoms
or signs of infection, and the cell shown in the photomicrograph of the patient’s blood is more
consistent with an alternative explanation for the abnormalities present.

Vitamin B12 deficiency

Try another choice.

Either folate or vitamin B12 deficiency may be associated with the development of pancytopenia, as well
as with marked elevation in the plasma lactate dehydrogenase level (LDH). The latter effect is related to
intramedullary hemolysis that occurs in megaloblastic anemia. However, neither folate nor vitamin
B12 deficiency is associated with a consumptive coagulopathy and low fibrinogen levels. In addition, the
MCV in this patient is normal and there are no hypersegmented neutrophils observed. Instead, there are
many blasts in the peripheral blood.

Acute lymphoid leukemia

Try another choice.

Although acute lymphoid leukemia can present with pancytopenia, it is not frequently associated with
evidence of significant disseminated intravascular coagulation at presentation. In addition, the cell
shown in the photomicrograph has features that indicate that its origin is not from the lymphoid lineage.

Acute myeloid leukemia

Correct.
Acute myeloid leukemia may present with pancytopenia, leukocytosis, or a white blood cell count within
the normal range. In addition, sometimes when pancytopenia is present, there are no circulating blasts,
although many may be found in the bone marrow (this is called aleukemic leukemia). In this case, the
combination of pancytopenia with blasts combined with the consumptive coagulopathy (disseminated
intravascular coagulation, DIC) indicates a diagnosis of acute myeloid leukemia. The cell shown in the
photomicrograph of the peripheral blood is a myeloblast that has a heavily granulated cytoplasm. The
stick-like inclusions in the cytoplasm are Auer rods. These are stacks of lysosomes that have collapsed on
one another to form linear structures within the cytoplasm. They are indicative of a myeloid disorder
and are seen only in acute myeloid leukemia and advanced myelodysplastic syndromes. The latter are
disorders that tend to transform into acute myeloid leukemia.
The bone marrow aspirate and biopsy findings become available, along with the flow
cytometric analysis documenting acute promyelocytic leukemia (APL, also known as M3
AML by the older French-American-British Classification scheme):

Morphology
The bone marrow aspirate shown (1) is notable for sheets of cells of similar morphology. The
cells are most akin to promyelocytes as their normal counterparts. However, the presence of
Auer rods distinguishes them as myeloblasts.

A bone marrow biopsy (2) reveals that the bone marrow space is hypercellular at 80% (normal is
about 40 to 60% for an adult, dependent on age) and occupied nearly completely by the blasts.
Note that in contrast to the bone marrow aspirate, which shows the morphology of individual
cells nicely, the bone marrow biopsy reveals an in situ sampling of the cells present. It is a core
of bone tissue that is decalcified, paraffin embedded, and sectioned prior to staining.

Histochemistry
This patient’s leukemia cells are positive for myeloperoxidase and negative for staining with
non-specific esterase and periodic acid-Schiff stain.

Such histochemistry can facilitate the distinction between various types of acute leukemia,
including the distinction between subsets of myeloid leukemia. It is used somewhat less
frequently today than previously, due to the widespread adoption of flow cytometry in leukemia
diagnostics.

Flow Cytometry
Flow cytometry is performed by staining the cells from a patient’s blood with fluorescently
labeled antibodies. The cells are then run through an instrument that sends them single file
through lasers that excite the fluorescent molecules on the antibodies. A detector collects the
light in order to determine which molecules are present on the cell surface. Additional
information can also be collected regarding cell size based upon light scatter. Thus, one can
identify the staining characteristics of different populations of cells present.

An example of the graphic output obtained, based on data from flow cytometry performed on a
sample, is provided in image (3). When the fluorescence from two different antibodies are
plotted against one another, it is possible to determine if one, both, or neither of the antigens is
present on the surface of the blasts. For example, the plot outlined in red looks at cluster of
differentiation antigen 33 (CD33) plotted against the HLA-DR antigen. The blasts cluster in the
lower right-hand box, indicating that they are positive for CD33 and negative for HLA-DR. This
is a defining characteristic of this patient’s leukemia.

Overall, the blasts present in bone marrow are found to have the following phenotype:

Present Absent
CD33 CD34
CD13 HLA-DR
CD117 CD11a
  CD11b
  CD18
The presence of CD33 and absence of CD34 and HLA-DR are consistent with a diagnosis of
acute promyelocytic leukemia (APL). The particular markers present also distinguish acute
lymphoid from acute myeloid leukemia and also distinguish different classes of myeloid
leukemias from one another.

Cytogenetic Analysis including Fluorescence in situ Hybridization (FISH)

Cytogenetic analysis and FISH analysis have become standard techniques in the analysis of acute
leukemia. Cytogenetic abnormalities, present in about 50% of cases of acute myeloid leukemia,
can have major prognostic implications. Cytogenetic abnormalities also have a major impact on
treatment decisions, including the type of chemotherapy administered and whether or not to
recommend hematopoietic stem cell transplantation in certain cases.

Cytogenetic analysis (4) and FISH (5) from a patient with APL are shown.

Giemsa banding of 20 metaphase chromosome spreads documents the presence of t(15;17)

translocation in 18 cells. FISH demonstrates the presence of a PML/RARA signal in 85% of 200
interphase nuclei examined.

Molecular Diagnostics
Using reverse transcriptase polymerase chain reaction (RT-PCR) on RNA prepared from the
patient’s white blood cells, a strong band is identified, indicating the presence of
the PML/RARA gene fusion.

Molecular diagnostic testing is becoming increasingly important in leukemia diagnosis. Besides

facilitating rapid diagnosis of known translocations, it identifies abnormalities in about 75% of
acute myeloid leukemia that is otherwise cytogenetically normal. As with cytogenetics,
identification of such abnormalities can have major prognostic significance. For example, in
otherwise cytogenetically normal acute myeloid leukemia, the finding of internal tandem
duplications in the FMS-like tyrosine kinase 3 gene (FLT3-ITD mutation) is associated with a
poor prognosis, whereas the finding of an isolated abnormality in the nucleophosmin 1 gene
(NPM1 mutation) is associated with a favorable overall prognosis.

Epidemiology
Acute myeloid leukemia (AML) is a relatively common hematologic malignancy. In the United
States in 2010, there were about 12,000 new cases and about 9,000 deaths from the disease. It
most commonly affects older individuals, with a median age of 68 years at diagnosis, but also
occurs across the entire age spectrum, including children.

Risk factors for AML include exposure to certain toxins, such as benzene, and exposure to
ionizing radiation. In addition, therapy-related AML occurs in a fraction of patients treated with
chemotherapy agents, particularly alkylating agents and topoisomerase II inhibitors. Certain
genetic abnormalities, such as Down’s syndrome and neurofibromatosis 1, are also associated
with an increased incidence of AML. Several other hematologic disorders ultimately can
transform into acute myeloid leukemia. These include the myelodysplastic syndromes,
myeloproliferative syndromes, and chronic myeloid leukemia.
Classification
Modern classification of AML relies on complementary modalities. These include evaluation of
morphology, histochemistry, flow cytometry, cytogenetics including fluorescence in situ
hybridization (FISH), and molecular diagnostic testing.

Based on morphology and histochemistry, AML was traditionally classified into eight major
subtypes according to the French-American-British classification scheme:

M0 Miniminally differentiated AML

M1 AML without maturation
M2 AML with maturation
M3 Promyelocytic leukemia
M4 Myelomonocytic leukemia
M5 Monocytic leukemia
M6 Erythroleukemia
M7 Megakaryoblastic leukemia

However, with the advances in the field, including a deeper appreciation of the importance of
cytogenetic and molecular prognostic factors, the most recent World Health Organization
(WHO) classification scheme focuses on factors that are more related to the underlying
pathophysiology and outcomes. The major categories are:

Acute myeloid leukemia with recurrent genetic abnormalities

Acute myeloid leukemia with myelodysplasia-related changes
Therapy-related acute myeloid leukemia
Acute myeloid leukemia, not otherwise specified

The category of AML with recurrent genetic abnormalities encompasses both favorable and poor
prognosis leukemias:

Category Prognosis
AML with t(8;21)(q22;q22); RUNX1-RUX1T1 Favorable
AML with inv(16)(p13.1q22) or t(16;16)(p13.1q22); CBFB-
Favorable
MYH11
APL with t(15;17)(q22;q23); PML-RARA Favorable
AML with t(9;11)(p22;q23); MLLT3-MLL Intermediate
AML with t(6;9)(p23;q34); DEK-NUP214 Unfavorable
AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 Unfavorable
AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1 Intermediate
Provisional entity: AML with mutated NPM1 Favorable
Provisional entity: AML with mutated CEBPA Favorable

The molecular pathogenesis of APL is now understood and is illustrated on this page. The fusion
protein consists of the promyelocytic leukemia gene (PML), a tumor suppressor normally found
in nuclear bodies, and the retinoid acid receptor alpha gene (RARA), a transcription factor that is
normally responsive to retinoid acid. The juxtaposition of these two genes produces a protein
that does not respond to the usual form of retinoic. However, it does respond to a specific type of
retinoic acid, all-trans retinoid acid, leading to restoration of gene transcription and thereby to
cellular differentiation. Interestingly, the substance arsenic trioxide leads to a similar effect
because it leads to aggregation and degradation of the PML-RARA fusion protein, thereby
promoting differentiation. Both ATRA and arsenic trioxide are now used for the treatment of
APL.

Any type of AML may be associated with disseminated intravascular coagulation (DIC).
However, APL is the form of AML most commonly associated with severe coagulopathy. In
fact, much of the mortality today from APL is the result of early deaths due to bleeding
complications such as hemorrhage into the brain. The mechanism for the coagulopathy relates to
substances that are released from the blasts into the circulation as they undergo cell death. These
proteins include tissue factor and other proteins, including those involved in fibrinolysis. The
release of these proteins leads to the generation of thrombin and to the formation and subsequent
breakdown of fibrin strands. The resultant coagulopathy may be apparent when patients first
present with APL. Alternatively, it may be manifest or can be greatly exacerbated at the time
conventional cytotoxic chemotherapy is initiated, since this leads to rapid cell death. Newer
treatments for APL that lead to differentiation of the blasts (all-trans retinoic acid and arsenic
trioxide) greatly lessen this complication.

Acute promyelocytic leukemia (APL) is a favorable risk leukemia that is now generally
associated with an approximately 80% five-year survival. However, because of the coagulopathy
with disseminated intravascular coagulation (DIC) that is commonly associated with it, the
highest risk for morbidity and mortality is during the initial presentation and treatment. Note that
any type of AML may present with concomitant DIC, though APL is most commonly associated
with this complication.

Because of the risk of bleeding complications, particularly hemorrhage into the brain, whenever
there is even a small suspicion from features of the presentation that a leukemia may be APL, it
is recommended that all trans retinoic acid (ATRA) be started empirically pending confirmation
of the diagnosis. Treatment with ATRA is associated with reduction or resolution of the DIC in
APL. One complication of its use is an infiltrate that may occur in the lungs, causing hypoxia.
This finding is a well-described complication, as the myeloid blasts undergo maturation induced
by ATRA, and is called differentiation syndrome. It may be prevented by concomitant treatment
of patients with corticosteroids. Following initial treatment with ATRA, initial chemotherapy,
called induction chemotherapy, is administered. This may consist of an anthracycline
chemotherapy drug such as daunorubicin or idarubicin, in combination with continuation of the
ATRA, until the patient achieves a complete remission, which usually takes about a month.
Following this, several additional cycles of chemotherapy are given to try to eliminate any
remaining leukemic cells. This is called consolidation. Finally, to further reduce the risk of
recurrence, patients are often treated with oral maintenance chemotherapy for two years. Note
that APL is the only type of acute myeloid leukemia for which maintenance chemotherapy has
been shown to be of benefit. For the rest, induction and consolidation chemotherapy is followed
either by observation or treatment with hematopoietic stem cell transplant.

This patient is treated with ATRA at presentation and receives induction chemotherapy. Within a
few days of starting chemotherapy, there are no more blasts present in the peripheral blood, and
the DIC resolves completely. About two weeks after starting chemotherapy, her white blood cell
count is barely detectable, and she develops a fever. Blood cultures are obtained, and she is
empirically started on broad spectrum antibiotics. After 2 days, her fever resolves; however, no
organism is ever identified from the blood cultures. Four weeks after starting treatment, her
blood counts recover toward normal. A bone marrow aspirate and biopsy is performed to assess
her response to the chemotherapy, and she is found to be in remission. She is then treated with
three cycles of consolidation chemotherapy over the next three months, followed by two years of
maintenance chemotherapy. When she returns to the clinic a year after completing all of her
treatments, she feels well and has no complaints. A molecular diagnostic test performed reveals
no evidence of the PML-RARA gene fusion.
Back Try Again Disp

1. The differential diagnosis for pancytopenia includes a wide variety of conditions,

including aplastic anemia, paroxysmal nocturnal hemoglobinuria, folate and vitamin
B12deficiency, myelophthisis (replacement of the marrow by fibrous tissue or by tumor
cells), and acute leukemia.
2. Acute myeloid leukemia may be associated with disseminated intravascular coagulation
(DIC, consumptive coagulopathy). Acute promyelocytic leukemia is the type of leukemia
most commonly associated with this, but DIC may occur in any subtype of acute myeloid
leukemia.
3. Acute myeloid leukemia is classified according to morphologic, histochemical, flow
cytometric, cytogenetic, and molecular diagnostic features. Today, cytogenetic and
molecular prognostic factors are crucial to categorizing patients into favorable,
unfavorable, and intermediate risk groups.
4. The categorization of acute myeloid leukemia is important because it facilitates
appropriate further management. Patients with favorable risk disease can be treated with
standard chemotherapy and avoid treatments that would not significantly improve their
overall survival, whereas patients with unfavorable risk disease can consider therapeutic
options such as hematopoietic stem cell transplant or clinical trials.
5. Acute promyelocytic leukemia, one of the favorable risk leukemias, is most commonly
associated with a t(15;17) translocation. This places the promyelocytic leukemia gene
(PML) in juxtaposition with the retinoic acid receptor alpha gene (RARA), creating
the PML-RARA fusion that impedes normal myeloid differentiation. Treatment of patients
with all trans retinoic acid (ATRA) overcomes this block to differentiation and is
associated with improvement in DIC and overall outcome when combined with
conventional chemotherapy.

Back Try Again