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CHRONIC LEUKEMIA
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The definition of chronic leukemia:

• Chronic leukemia is thought to arise from genetic

defect in a single cell in B.M or in the peripheral tissue.
When this cell success to proliferate gives rises to a
clonal population that will give mass which when
enlarged enough caused a serious disease.
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What Are the Types of Chronic

Leukemia?
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Classification of CL.

• There are two types:

1- chronic myeloid leukemia.

2- chronic lymphoid leukemia.
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Chronic Myeloid Leukemia.

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Definition of CML:
• CML is defined as a stem cell disorder suggested as
Philadelphia chromosome found in all stem cells. So there
is replacement of normal B.M cells by cells with an
abnormal chromosome – Philadelphia or (ph)
chromosome
t (9; 22)(q34; q11).

• Constitute six different types of leukemia.

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Incidence
• CML comprises <20% of all leukaemia, its rarer than
CLL.

• The incidence rate is 1-2/100,000-1 population; with a

peak of incidence in the middle age people.

• The disease occur in either sex (male: female 1.4:1),

however, it may occur in children, neonates and very
old people.
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What Is Philadelphia Chromosome?

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Philadelphia :
• Is the chromosome which result from the t(9;22)
(q34;q11)part of the Abelson proto-oncogene ABL is
moved to the BCR gene on chromosome 22 & part of
chromosome 22 moves to chromosome 9.

• The abnormal chromosome 22is the Ph.

• See fig.
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Fig
 Pathogenesis

Hematopoietic abnormality
●
Expansion of granulocytic progenitors and a decreased
sensitivity of the progenitors to regulation – increased
white cell count
●
Megakaryocytopoiesis is often expanded
●
Erythropoiesis is usually deficient
●
Function of the neutrophils and platelet is nearly normal
Translocation t(9;22)(q34;q11)
Translocation t(9;22)
(q34;q11)
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Clinical Presentation:
• Increasing splenomegally, which is associated with
discomfort, pain or indigestion.
• Refractory anaemia that include pallor, weakness and
tachychardia.
• Bruising, epistaxis due to abnormal platelet functions.
• Gout or renal impairment due to hyperuricemia.
• Visual disturbances.
• Increase requirement to chemotherapy to maintain
remission.
• Massive increasing of circulating granulocytes.
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How Would You Investigate the

Patient With Suspected CML?….
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Investigation:
• CBC:
Wbc is usually >50X10/l & some times >500X10/l.
Normocytic normochromic anemia.
Platelets .

• peripheral blood film:

 circulating basophil.
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fig
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Cont:
• Neutrophil alkaline phosphatase score is invariably low.
• BM: is hyper cellular with granulopoietic predominance.
• Cytogenetics: ph chromosome.
• Serum vitamin B12 & vitamin b12-binding capacity are.
• Serum uric acid is usually.
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What Are the Phases of CML?…

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Phases of CML:
• Chronic phase :
• Accelerated phase:
• Blast phase:
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Chronic phase CML

The three defining features of typical chronic phase are:

• Raised granulocytes.
• The presence of Philadelphia chromosome.
• Splenomegaly.
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Accelerated phase CML

The transition to accelerated phase is accompanied by increasing
refractoriness to treatment which may be reflected in one or more
of the following changes:

• >15% blasts in B.M or peripheral blood.

• >30% blasts + promyelocyte in peripheral blood.
• >20% basophil in peripheral blood.
• <100,000/m3 platelet.
• Additional chromosome abnormality (+8) trisomy.
• Increase B.M fibrosis.
• In blastic phase the blast should exceed 30% in the peripheral
blood (blastic crisis) , which is an evolution of CML that give rise
to acute phase, this is manifested by progression of anaemia ,
neutropenia and thrombocytopenia.
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Blastic phase CML

• In most cases, establishment of the accelerated phase of
CML is followed by a sustained refractory to treatment,
the blast cell count rises and physical symptoms are
worsening. The diagnostic criteria for blast crisis are that
the circulating blast cell counts should exceed 30% of the
total leukocyte count.

• Progression of chronic phase to blastic phase has been

likened to the evolution of chronic leukaemia into acute
leukaemia. The accumulation of blast cells which results
is accompanied by anaemia, neutropenia and
thrombocytopenia
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Chronic lymphocytic Leukemia:

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CLL
• CLL is the most common of the chronic lymphoid
leukemias.

• Is characterised by the accumulation of non-proliferation

mature-appearing lymphocytes (Lymphocytosis) in the
blood, marrow, lymph nodes, and spleen.
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CLL
• In most cases, the cells are monoclonal B lymphocytes
that are CD5+
• T cell CLL can occur rarely
• Peak incidence between 60-80yrs.
• Is the most common form of leukemia in North
America and Europe, but is extremely rare in the
Orient
• Affects men twice as often as women
• Incidence rate: 300 cases / 100,000-1 population/
annually.
Clinical presentation:
• The disease is slow progressive
• 25% of the cases are free of physical symptoms at
diagnosis.
• Unexplained absolute and persistent
lymphocytosis; cervical, supclavicular, and/or
axillary lymphadenopathy; and splenomegaly are
the earliest signs.
• Chronic fatigue, recurrent or persistent infections,
and easy bruising are consequences of anaemia,
neutropenia, B-cell immunolgical dysfunction, and
thrombocytopenia.
• Hepatomegaly may accompanied splenomegaly.
• Leukaemic lymphocytes may invade unusual
locations such as the scalp, orbits,
subconjunctivae, gums, pleural and lung
parenchyma, prostate, and gonads.
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Fig(1)
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Fig(2)
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How would you investigate patient

with CLL?..
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Investigation:

• CBC:
• Wbc:
• Diff: lymphocytosis ,the absolute lymphocyte count is >5x10 9/l
and may be up to 300x109/l or More.
Anemia: normocytic normochromic anemia is present in later
stages, autoimmune haemolysis.
Platelets : thrombocytepenia may occur.
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Cont:
Blood film:
70-99% of white cells mature lymphocyte.
Smudge or smear cells also present.
Immunophenotyping:
Shows that the lymphocyte are B cells(CD19)expressing one form
of light chain( or only)cells are also CD5&CD23+ve.
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Fig(3)
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Cont:
• Bone marrow aspiration:
Lymphocytic replacement of normal marrow.
• Immunoglobulin electrophoresis:
 of Ig more marker with advance disease.
• Cytogenetic :
The 4 most common abnormalities are; deletion of
13q14,trisomy 12, deletion of11q23&structural
abnormality of 17p involving the p53 gene.
Prognosis
• 50% of the patients will receive partial remission.
• < 30% of the patients will got complete remission.
• 30% of the cases will transfer into PLL.
• 5% of the cases will have Richters syndrome in which
the blastic phase of CLL in lymph nodes.
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Thank you....................