Chronic leukaemias
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Transcript of Chronic leukaemias
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Chronic leukaemias
Chronic myelogenous leukaemiaChronic lymphocytic leukaemia
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Chronic leukaemias
Chronic myelogenous leukaemiaChronic lymphocytic leukaemia
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Chronic myelogenous leukaemia
A Myeloproliferative disorderA clonal disorder where 95% of patients
have a distinctive cytogenetic abnormality “the Philadelphia (Ph) chromosome”
Median age of ph+ CML is 67 yrs(30-80yrs)
Medial survival is 4-6 yrs, (range 1-10yrs)Curative only by BMT
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Myeloproliferative disorders
Chronic myelogenous leukaemiaPolycythemia VeraMyelofibrosisEssential thrombocythemia
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CML – Natural History Chronic phase:
Disease respond to treatment < 5% of blasts and promyelocytes in the peripheral
blood and bone marrow
Accelerated phase > 5% in either peripheral blood or bone marrow and <
20% in both peripheral blood and bone marrow. Blast crisis acute leukaemia
> 20% blasts are present in peripheral blood or bone marrow
70% AML 30% ALL
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CML- SymptomsFatigueAbdominal fullness and discomfort Symptoms of anaemiaNight sweatingLow grade feverWhen WBC count is very high
“leukostasis”• Blurred vision• Respiratory distress• priapism
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CML- SignsSplenomegaly ;
mild to gross, usually marked
10% have normal spleenSternal tendernessSigns of anaemia
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Philadelphia chromosome 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
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CML- InvestigationsComplete blood countPeripheral blood film smearBone marrow aspirationPh chromosome analysisOthers
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CML- InvestigationsComplete blood countPeripheral blood film smearBone marrow aspirationSouthern Blot analysisPh chromosome analysisNAP scoreOthers
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Complete blood count
WBC countsIt may reach up to 500 x 109/lUsually around 150 x 109/l
AnaemiaPlatelets N or
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CML- InvestigationsComplete blood countPeripheral blood film smearBone marrow aspirationPh chromosome analysisOthers
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Peripheral blood film smear Shift to left of myeloid series with more myelocytes in PBF
than mature WBCs
Blast cells are < 5% Basophilia
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PBF in CML
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CML- InvestigationsComplete blood countPeripheral blood film smearBone marrow aspiration
Assess cellularityAssess fibrosisCytogenetic studies for Ph chromosome analysis
Others
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CML - Bone marrow aspiration Hyper cellular bone marrow
Shift in the myeloid series to immature forms, this increase in number as patients progress to blastic phase of the disease.
Myeloblast count <5% of myeloid cells in chronic phase.
Elevated myeloid/ erythroid ratio in the marrow.
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CML- Investigations Complete blood count Peripheral blood film smear Bone marrow aspiration
Assess cellularity Assess fibrosis Cytogenetic studies for Ph chromosome analysis
Others Vitamin B12 level due to secretion of
transcobolamin III Uric acid
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Management of Chronic CMLGleevec® (Imatinib mesylate)
A tyrosine kinase inhibitorTyrosine kinase is required for transforming
functioin of the bcr-able fusion proteinIt induces hematological remission in almost
all patients with interferon resistent CMLCytogenetic response is seen in 50% of
patients.
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Management of Chronic CMLAllogenic 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.
Interferon αUsed for patients who are not eligible for BMTMay induce a cytogenetic response in 20% of
patients.
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Management of Chronic CML Hydroxurea
Uses: Initial treatment to lower WBC count prior to interferon
therapy. Palliative treatment of patients failing other treatment.
Splenectomy Hypersplenism discomfort
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Accelerated phase of CMLFeatures
Bone painSpleenomegalyResistance to current treatmentProgressive anaemiaThrombocytopenia or thrombocytosisBlast cells >5% in either PB or BM and <30%
of both PB and BM.
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Accelerated phase of CML
TreatmentImatinib mesylate
Bone marrow transplantation
High dose cytarabine
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Blastic phase of CML
FeaturesFeverMalaiseProgressive splenomgalyBlast cells >20% in PB or BM
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Blastic phase of CML
TreatmentImatinib mesylate
As in ALL (Vincrisitne and prednisolone + anthracycline)
Allogenic BMT
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Chronic lymphocytic leukemia It is a disease of
morphologically mature but immunologically less mature lymphocytes.
Manifested by progressive accumulation of lymphocytes in the blood, bone marrow and lymphatic tissues.
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CLLEpidemiology
The most common leukemia in adultmales >females> 45 yrsHere mature lymphocytes fail to respond to
Ag stimulation95% are B cell type5% are T cell type
The overall 5 year survival is 60%
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CLLClinical presentation
Indolent lymphocytosis (asymptomatic)
Generalized lymphadenopathy
Hepato-splenomegaly
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CLLClinical presentation
Pancytopenia Anaemia
Coombs positive hemolysis Hypoplastic
Bleeding Production thrombocytopenia Immune thrombocytopenia
Infection Depressed immunoglobulin levels
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CLLinvestigations
CBCPBFBM aspiration Immunochemistry Total protein and Ig level
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CBCPBFBM aspiration immunochemistryTotal protein and Ig level
CLLinvestigations
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WBC: Increased counts Mainly lymphocytes Lymphocyte count >=10 x 109/l
Hb: Normal or low Hemolytic anaemia
Platelets: Normal or low
Complete blood counts
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CBCPBFBM aspiration Immunochemistry Total protein and Ig level
CLLinvestigations
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Perioheral blood film Predominantly
lymphocytosis Normally looking Presence of smudge cells
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CBCPBFBM aspiration Immunochemistry Total protein and Ig level
CLLinvestigations
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Not necessary for diagnosis
Infiltration of the bone marrow by lymphocytes.
Bone marrow aspiration
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CBCPBFBM aspiration Immuno chemistryTotal protein and Ig level
CLLinvestigations
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Immunoglobulin levelsLow immunoglobulin levels
Immuno-chemistry
•CD19 positive•CD20 positive•CD5 positive
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CLL- staging
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CLLwhom to treat?
Stage A No TreatmentObservation only
Stage B Treat if symptomaticObservation only for asymptomaticChemotherapy for symptomatic
lymphadenopathy
Stage C Treat AllShould be treated
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CLLtreatment
Supportive treatment Treat infection
Herpes zoster Pseudomonas carinii
Proper hydration + allopurinol
Automimmune anaemia or thrombocytopenia corticosteroids Blood transfusion High dose immuneglobulin Cyclosporine Splenectomy Low dose radiation to the spleen
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CLLTreatment options
Oral alkylating agents + corticosteroids Chlorambucil + prednisolone
Purine analogues: Fludrabine,
Combination chemotherapy: CVP or CHOP
Involved field radiotherapy: for lymph node areas
Splenic radiation for palliation of hypersplenism