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Essentials of Diagnosis

Short duration of symptoms, including


fatigue, fever, and bleeding.
Cytopenias or pancytopenia.
More than 20% blasts in the bone marrow.
Blasts in peripheral blood in 90% of
patients.
Classify as acute myeloid leukemia (AML)
or acute lymphoblastic leukemia (ALL).
General Considerations

Acute leukemia is a hematopoietic


progenitor cell malignancy.
Uncontrolled proliferation cells and replace
normal bone marrow elements.
Arise with no clear cause. However,
radiation and some toxins (benzene) are
leukemogenic. A number of
chemotherapeutic agents (especially
cyclophosphamide, melphalan, other
alkylating agents, and etoposide) may
cause leukemia.
General Considerations

Most of the clinical findings in acute


leukemia are due to replacement of
normal bone marrow elements by the
malignant cell.
Less common manifestations result from
organ infiltration (skin, gastrointestinal
tract, meninges).
Acute leukemia is potentially curable
with combination chemotherapy.
General Considerations

ALL comprises 80% of the acute leukemias


of childhood. The peak incidence is
between 3 and 7 years of age. It is also
seen in adults, causing approximately 20%
of adult acute leukemias.
Acute myeloid leukemia (AML) is primarily
an adult disease with a median age
Symptoms and Signs

Bleeding (usually due to thrombocytopenia) :


Skin
Mucosal surfaces
Ginggival bleeding
Epistaxis
Menorrhagia
Less commonly, widespread bleeding is
seen in patients with disseminated
intravascular coagulation (DIC).
Symptoms and Signs

Infection is due to neutropenia (falls below)


500/mcL. The most common pathogens
are gram-negative bacteria (Escherichia
coli, Klebsiella, Pseudomonas) or fungi
(Candida, Aspergillus). Common
presentations include cellulitis, pneumonia,
and perirectal infections; death within a few
hours may occur if treatment with
appropriate antibiotics is delayed.
Symptoms and Signs

Patients may also seek medical attention :


Gum hypertrophy
Bone and joint pain
The most dramatic presentation is
hyperleukocytosis, in which a markedly
elevated circulating blast count (usually >
200,000/mcL) leads to impaired circulation :
Headache
Confusion
Dyspnea
Laboratory Findings

The hallmark of acute leukemia is the


combination of pancytopenia with
circulating blasts
However, blasts may be absent from the
peripheral smear in as many as 10% of
cases ("aleukemic leukemia").
The bone marrow is usually hypercellular
and dominated by blasts. More than 20%
blasts are required to make a diagnosis of
acute leukemia.
Laboratory Findings
Hyperuricemia may be seen.
If DIC is present :
The fibrinogen level will be reduced
The prothrombin time prolonged
Fibrin degradation products or fibrin D-dimers
present.
Patients with ALL (especially T cell) may have a
mediastinal mass visible on chest radiograph.
Meningeal leukemia will have blasts present in the
spinal fluid, seen in approximately 5% of cases at
diagnosis; it is more common in monocytic types of
AML.
The Auer rod, an eosinophilic needle-like inclusion in
the cytoplasm, is pathognomonic of AML
Laboratory Findings
AML classification by "FAB," (French,
American, British) was based of morphology
and histochemistry :
Acute undifferentiated leukemia (M0)
Acute myeloblastic leukemia (M1)
Acute myeloblastic leukemia with
differentiation (M2)
Acute promyelocytic leukemia (APL) (M3)
Acute myelomonocytic leukemia (M4)
Acute monoblastic leukemia (M5)
Erythroleukemia (M6)
Megakaryoblastic leukemia (M7)
Differential Diagnosis

AML must be distinguished from other


myeloproliferative disorders :
Chronic myeloid leukemia
Myelodysplastic syndromes.
ALL must be separated from other
lymphoproliferative disease such as :
Chronic lymphocytic leukemia
Lymphomas
Hairy cell leukemia.
Atypical lymphocytosis of mononucleosis
and pertussis.
Treatment

The first step in treatment is to obtain


complete remission :
normal peripheral blood with resolution
of cytopenias
normal bone marrow with no excess
blasts
normal clinical status.
The type of initial chemotherapy depends
on the subtype of leukemia.
AML

AML are treated with a combination :


anthracycline (daunorubicin or idarubicin) plus
cytarabine, either alone or in combination with
other agents.
This therapy will produce complete remission in 80%
of patients under age 60 years and in 5060% of
older patients.
APL is treated differently from other forms of AML.
Induction therapy should include anthracycline plus
all-trans-retinoic acid.
With this approach 9095% of patients will achieve
complete remission.
ALL
Adults with ALL are treated :
Daunorubicin
Vincristine
Prednisone
Asparaginase
This treatment produces complete
remissions in 90% of patients.
Remission induction therapy for ALL is less
myelosuppressive than treatment for AML
and does not necessarily produce marrow
aplasia
Prognosis
Approximately 7080% of adults with AML under age 60
years achieve complete remission.
High-dose postremission chemotherapy leads to cure in
3540% of these patients, and high-dose cytarabine has
been shown to be superior to therapy with lower doses.
Allogeneic bone marrow transplantation is curative in 50
60% of cases.
Autologous bone marrow transplantation may be superior
to nonablative chemotherapy.
Older adults with AML achieve complete remission in up
to 50% of instances.
The cure rates for older patients with AML have been very
low (approximately 1015%) even if they achieve
remission and are able to receive postremission
chemotherapy.