Chronic Leukemias

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Chronic Leukemias
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C M L
C L L
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CML
A clonal disease results from an acquired genetic
change in a pluri-potential hemopoietic stem cell
within the BM. The altered stem cell
proliferates and generates a population of
differentiated cells that gradually replace
normal hemopoiesis.
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CML
The disease is bi-phasic or tri-phasic with
a i) A chronic phase ii) An acute phase,
and iii) Sometimes an intervening accelerated
phase.
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The characteristic findings in
CML ?Laboratory CML usually diagnosed in the
initial chronic indolent phase. The WBC count
at diagnosis is usually in the range 20-200
109/L Occasionally, patients may present with
leukocyte numbers in the range 200-800
109/L. a) PB The blood film shows a full
spectrum of cells in the granulocyte series,
FROM blast cells TO mature neutrophils BUT
intermediate myelocytes and neutrophils
predominate. b) BM Hypercellular marrow,
increased ME ratio. ?Clinical anemia is usual
and huge splenomegaly is frequently seen.
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The peripheral blood film in patients with CML,
may show VARING cells as promyelocytes
(P) myelocyte (M) eosinophil (E) basophil
(B) (NUMEROUS) neutrophils (N) band forms (BF)
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P
M
N
E
P
B
BF
BF
BF
A peripheral blood film in a patient with (CML)
diagnosis
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The fusion gene BCR-ABL, that was originally
detected by cytogenetics studies, today is
routinely used in CML in most centers around the
world (BUT NOT HERE).
Found in gt95 of CML cases
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CLL
As the disease state is mostly silent and with an
insidious onset, incidental diagnosis now occurs
in 70-80 of patients.
CLL is a chronic B-lineage lymphoproliferative
disorder (LPD) defined by characteristic
morphology and immunophenotyping findings. The
cell of origin in CLL is now thought to be an
activate B-cell that has undergone somatic
hypermutation of IGVH genes. Much common in the
western hemisphere than us.
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How to Diagnose CLL?

• a lymphocyte count of at least 5 109/L (5,000
  cells per cubic mm) was sufficient for diagnosis
  when
• The immunophenotype was typical (CD19/CD5).
• B-cell clonality was demonstrated (Monoclonal
  B-cell lymphocytosis)
• the proliferated cells express either Kappa
  or Lambda BUT NOT BOTH.

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PB finding in a patient with CLL
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RAI clinical staging of CLL
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Hairy Cell Leukemia
It is always associated with splenomegaly, which
tends to progress slowly. Lymph node enlargement
is usually absent. BM aspirates are unsuccessful
as no fragments and few cells are obtained.
?Trephine BM biopsy is essential.
?Most cases present hematologically with
leukopenia, neutropenia, and typically with
monocytopenia. It usually affects males THAN
female and above age 40.
Splenomegaly, Hepatomegaly, Pancytopenia, Hairy
lymphocytes
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How to Diagnose Hairy Cell Leukemia
The recognition of typical hairy cells in PB
films is useful for suggesting this diagnosis.
Hairy cells are large, twice the size of a
normal lymphocyte, and have abundant cytoplasm,
that is characteristically villous in its outline
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Tartrate-resistant acid phosphatase (TRAP)
demonstrated on hairy cells corresponds to a
unique isoenzyme and is specific for HCL. This
enzyme can be used in BM biopsy.
Tartrate-resistant acid phosphatase (TRAP)
activity in three hairy cells