Transcript Chronic leukaemias

Chronic leukaemias
Chronic
myelogenous leukaemia
Chronic lymphocytic leukaemia
Chronic leukaemias
Chronic
myelogenous leukaemia
Chronic lymphocytic leukaemia
Chronic myelogenous leukaemia
A Myeloproliferative disorder
 A clonal disorder where 95% of patients
have a distinctive cytogenetic abnormality
“the Philadelphia (Ph) chromosome”
 Median age of ph+ CML is 67 yrs(3080yrs)
 Medial survival is 4-6 yrs, (range 1-10yrs)
 Curative only by BMT
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Myeloproliferative disorders
Chronic myelogenous leukaemia
 Polycythemia Vera
 Myelofibrosis
 Essential thrombocythemia
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CML – Natural History
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Chronic phase:
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Accelerated phase
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Disease respond to treatment
< 5% of blasts and promyelocytes in the peripheral
blood and bone marrow
> 5% in either peripheral blood or bone marrow and <
20% in both peripheral blood and bone marrow.
Blast crisis  acute leukaemia
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> 20% blasts are present in peripheral blood or bone
marrow
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70% AML
30% ALL
CML- Symptoms
Fatigue
 Abdominal fullness and discomfort
 Symptoms of anaemia
 Night sweating
 Low grade fever
 When WBC count is very high
“leukostasis”
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•Blurred vision
•Respiratory distress
•priapism
CML- Signs
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Splenomegaly ;
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mild to gross, usually
marked
10% have normal spleen
Sternal tenderness
 Signs of anaemia
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Philadelphia chromosome
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A cytogenetic abnormality
Due to reciprocal translocation
between the long arm of
chromosomes 9(9q) and
22(22q) (9:22 translocation)
It is found in all haematopoietic
precursors of CML patients.
This result in the transfer of the
Abelson's (abl) oncogene to an
area of chromosome 22
termed the break-point cluster
region (bcr)
This results in a fused bcr-abl
gene and production of an
abnormal tyrosine kinase
protein.
This protein causes disordered
myelopoiesis in CML
CML- Investigations
Complete blood count
 Peripheral blood film smear
 Bone marrow aspiration
 Ph chromosome analysis
 Others
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CML- Investigations
Complete blood count
 Peripheral blood film smear
 Bone marrow aspiration
 Southern Blot analysis
 Ph chromosome analysis
 NAP score
 Others
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Complete blood count
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 WBC counts
9
It may reach up to 500 x 10 /l
9
 Usually around 150 x 10 /l
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Anaemia
 Platelets N or 
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CML- Investigations
Complete blood count
 Peripheral blood film smear
 Bone marrow aspiration
 Ph chromosome analysis
 Others
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Peripheral blood film smear
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Shift to left of myeloid series with more myelocytes in PBF
than mature WBCs
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Blast cells are < 5%
Basophilia
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PBF in CML
CML- Investigations
Complete blood count
 Peripheral blood film smear
 Bone marrow aspiration
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 Assess
cellularity
 Assess fibrosis
 Cytogenetic studies for Ph chromosome analysis
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Others
CML - Bone marrow aspiration
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Hyper cellular bone marrow
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Shift in the myeloid series to immature forms,
this increase in number as patients progress to
blastic phase of the disease.
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Myeloblast count <5% of myeloid cells in chronic
phase.
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Elevated myeloid/ erythroid ratio in the marrow.
CML- Investigations
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Complete blood count
Peripheral blood film smear
Bone marrow aspiration
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Assess cellularity
Assess fibrosis
Cytogenetic studies for Ph chromosome analysis
Others
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 Vitamin B12 level due to  secretion of
transcobolamin III
 Uric acid
Management of Chronic CML
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Gleevec® (Imatinib mesylate)
A tyrosine kinase inhibitor
 Tyrosine kinase is required for transforming
functioin of the bcr-able fusion protein
 It induces hematological remission in almost
all patients with interferon resistent CML
 Cytogenetic response is seen in 50% of
patients.
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Management of Chronic CML
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Allogenic BMT
Is the only curative treatment available of
CML so far
 It should be considered in the first year of
diagnosis if the patient is <40 yrs of age and
has an HLA matched donor.
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Interferon α
Used for patients who are not eligible for BMT
 May induce a cytogenetic response in 20% of
patients.
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Management of Chronic CML
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Hydroxurea
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Uses:
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Initial treatment to lower WBC count prior to interferon
therapy.
Palliative treatment of patients failing other treatment.
Splenectomy
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Hypersplenism
discomfort
Accelerated phase of CML
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Features
Bone pain
 Spleenomegaly
 Resistance to current treatment
 Progressive anaemia
 Thrombocytopenia or thrombocytosis
 Blast cells >5% in either PB or BM and <30%
of both PB and BM.
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Accelerated phase of CML
 Treatment
 Imatinib
 Bone
 High
mesylate
marrow transplantation
dose cytarabine
Blastic phase of CML
 Features
 Fever
 Malaise
 Progressive
splenomgaly
 Blast cells >20% in PB or BM
Blastic phase of CML
 Treatment
 Imatinib
 As
mesylate
in ALL (Vincrisitne and prednisolone + anthracycline)
 Allogenic
BMT
Chronic lymphocytic leukemia
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It is a disease of
morphologically mature but
immunologically less mature
lymphocytes.
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Manifested by progressive
accumulation of lymphocytes
in the blood, bone marrow
and lymphatic tissues.
CLL
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Epidemiology
The most common leukemia in adult
 males >females
 > 45 yrs
 Here mature lymphocytes fail to respond to
Ag stimulation
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 95%
are B cell type
 5% are T cell type
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The overall 5 year survival is 60%
CLL
Clinical presentation
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Indolent lymphocytosis
(asymptomatic)
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Generalized lymphadenopathy
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Hepato-splenomegaly
CLL
Clinical presentation
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Pancytopenia
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Anaemia
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Bleeding
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Coombs positive hemolysis
Hypoplastic
Production thrombocytopenia
Immune thrombocytopenia
Infection
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Depressed immunoglobulin levels
CLL
investigations
CBC
 PBF
 BM aspiration
 Immunochemistry
 Total protein and Ig level
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CLL
investigations
CBC
 PBF
 BM aspiration
 immunochemistry
 Total protein and Ig level
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Complete blood counts
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WBC:
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Hb:
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Increased counts
Mainly lymphocytes
9
Lymphocyte count >=10 x 10 /l
Normal or low
Hemolytic anaemia
Platelets:
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Normal or low
CLL
investigations
CBC
 PBF
 BM aspiration
 Immunochemistry
 Total protein and Ig level
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Perioheral blood film
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Predominantly
lymphocytosis
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Normally looking
Presence of smudge cells
CLL
investigations
CBC
 PBF
 BM aspiration
 Immunochemistry
 Total protein and Ig level
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Bone marrow aspiration
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Not necessary for diagnosis
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Infiltration of the bone marrow by
lymphocytes.
CLL
investigations
CBC
 PBF
 BM aspiration
 Immuno chemistry
 Total protein and Ig level
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Immuno-chemistry
•CD19 positive
•CD20 positive
•CD5 positive
Immunoglobulin levels
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Low immunoglobulin levels
CLL- staging
CLL
whom to treat?
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Stage A  No Treatment
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Observation only
Stage B  Treat if symptomatic
Observation only for asymptomatic
 Chemotherapy for symptomatic
lymphadenopathy
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Stage C  Treat All
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Should be treated
CLL
treatment
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Supportive treatment
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Treat infection
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Herpes zoster
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Pseudomonas carinii
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Proper hydration + allopurinol
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Automimmune anaemia or thrombocytopenia
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corticosteroids
Blood transfusion
High dose immuneglobulin
Cyclosporine
Splenectomy
Low dose radiation to the spleen
CLL
Treatment options
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Oral alkylating agents + corticosteroids
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Chlorambucil + prednisolone
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Purine analogues: Fludrabine,
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Combination chemotherapy:
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CVP or CHOP
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Involved field radiotherapy: for lymph node
areas
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Splenic radiation for palliation of hypersplenism