LEUKEMIAS
Definition
Neoplastic clonal proliferation of the haemopoetic cell
lines in the bone marrow with release into circulation of
abnormal cells.
Classification
Based on clinical presentation
Acute-Rapid onset and progression and without
treatment death in few months 2-3 months.
Acute leukemia’s have arrested maturation of the
haemopoetic cells with predominance of blast cells in
circulation.
Chronic-Insidious onset and slow progressing and
without treatment death in months to years.
Mature cells and some blasts in circulation-maturation
spectrum of cells.
Based on cell types
Lymphoid
Myeloid types.
ACUTE LYMPOBLASTIC LEUKEMIA
Definition
ALL- is a malignant (clonal) proliferation of early
lymphoid precursors in the bone marrow with
replacement the normal hematopoietic cells of the
marrow.
Pathophysiology:
-The malignant cells of ALL are lymphoid precursor
cells (ie, lymphoblast) that are arrested in an early stage
of development.
-This arrest is caused by an abnormal expression of
genes, often as a result of chromosomal translocations.
-The lymphoblasts replace the normal marrow elements,
resulting in a marked decrease in the production of
normal blood cells. Consequently, anemia,
thrombocytopenia, and neutropenia occur to varying
degrees.
-The lymphoblasts also proliferate in organs other than
the marrow, particularly the liver, spleen, and lymph
nodes.
Frequency:
ALL is the most common type of leukemia in children.
In adults, it is less common than acute myelogenous
leukemia (AML)
Mortality/Morbidity:
Only 20-40% of adults with ALL are cured with current
regimens.
ALL in pediatrics is more responsive.
Sex:
ALL is slightly more common in men than in women.
Age:
ALL is more common in children than in adults
Physical:
-Patients commonly have physical signs of anemia,
including pallor and a cardiac flow murmur.
-Fever and other signs of infection, including lung
findings of pneumonia, can occur.
-Thrombocytopenia usually demonstrate petechiae,
particularly on the lower extremities.
A large number of ecchymoses is usually an indicator of
a coexistent coagulation disorder such as DIC.
-Signs relating to organ infiltration with leukemia cells
include hepatosplenomegaly and, to a lesser degree,
lymphadenopathy.
-Occasionally, patients have rashes resulting from
infiltration of the skin with leukemic cells.
History:
Patients with ALL present with either
(1) Symptoms relating to direct infiltration of the
marrow or other organs by leukemia cells or
(2) Symptoms relating to the decreased production of
normal marrow elements.
-Infiltration of the marrow by massive numbers of
leukemia cells frequently manifests as bone pain.
This pain can be severe and is often atypical in
distribution.
-Uncommonly (10-20%), patients may present with left
upper quadrant fullness and early satiety due to
spenomegaly.
-Other patients, particularly those with T-cell ALL,
present with symptoms related to a large mediastinal
mass, such as shortness of breath.
-Symptoms of leukostasis (eg, respiratory distress,
altered mental status) because of the presence of large
numbers of lymphoblasts in the peripheral circulation,
leukostasis is much less common in persons with ALL
compared to AML and occurs only in patients with the
highest WBC counts, ie, several hundred thousand per
microliter.
-Symptoms of anemia are common and include fatigue,
dizziness, palpitations, and dyspnea upon even mild
exertion.
-Patients with ALL often have decreased neutrophil
counts, despite an increased total WBC count have
increased risk of infection.
-Patients with ALL often have fever without any other
evidence of infection.
However, in these patients, one must assume that all
fevers are from infections until proven otherwise
because a failure to treat infections promptly and
aggressively can be fatal. Infections are still the most
common cause of death in patients undergoing treatment
for ALL
-Bleeding symptoms due to thrombocytopenia .The
thrombocytopenia, however, tends to be less severe than
that observed in patients with AML
-Some may have (DIC) at the time of diagnosis, usually
as a result of sepsis.
Consequently, some patients may present with
hemorrhagic or thrombotic complications.
-Signs relating to leukostasis include respiratory
distress and altered mental status
Procedure
Bone marrow aspiration and biopsy are the definitive
diagnostic tests to confirm the diagnosis of leukemia.
Tests
Cytochemical Staining
Positive TdT- terminal deoxynucleotidyl transferase and
PAS (Periodic Acid Schiff) is the hallmark of ALL. ALL
is negative to myeloperoxiadase and Sudan black
TdT also helps distinguish ALL from malignancies of
more mature lymphocytes (ie, NHL).
Immunophenotying /Flow cytometry-Cell markers
Positive confirmation of lymphoid (and not myeloid)
lineage by flow cytometric demonstration of lymphoid