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Chronic Leukimia
Chronic Leukimia
Chronic Lymphocytic
Leukemia
( CLL )
Overview
Definition
Incidence
Etiology
Clinical features and presentation
Diagnosis
Management and prognosis
Definition
Progressive accumulation of mature appearing,
functionally
incompetent,
long-lived B lymphocytes in peripheral
blood, bone marrow, lymph nodes,
spleen, liver and sometimes other
organs.
Incidence
Commonest leukemia in Western
adults (25-30% of all leukemia).
2.5 / 100.000 per annum.
Predominantly disease of elderly
(in over70s, more than
20/100.000).
Median age at diagnosis 65 years.
Ratio of Male : Female = 2:1
Etiology
Unknown
No causal relationship with
radiation, chemicals or viruses.
Small proportion are familial.
Genetic factors suggested by low
incidence in Japanese even after
imigration.
90% of CLL cases have high levels of
BCL-2 which block apoptosis.
CBC
With more advance disease: lymphadenopathy: painless, often
general malaise
Autoimmune phenomen occur: DAT (+ve) 10-20% cases, warm
Diagnosis
CBC
Blood Film
Immunophenotyping
Bone Marrow
Lymph Biopsy
Cytogenetics
Prognosis
CLL remains incurable disease
A minority (10%) develop high grade NHL
(Richter sydrome): median interval from
diagnosis 24 months; associated with all
stages; abrupt onset; chemoresistant; median
survival 4 months.
Second malignancy (skin, colon) occur in up to
20%.
* Insidence : 1-1,4/100.000/yrs
* Age: Every age, > adults
Clinical manifestation:
* There are 2 phases:
a. Chronic phase
b. Acute Transformation - blast crisis
Citogenetic
> 95% : Philadelphia chromosome: +ve
Chromosome translocation of 9 dan 22 t ( (,22)
* Fusion oncogen ABL and BCR
* chimeric protein p 210 and 190
cell proliferation
Acute Transformation :
a. Accelerated phase - 6 months
b. Blast crisis several weeks
Biology of CML
Bcr-abl protein is a deregulated
tyrosine kinase with increased activity
Bcr-abl protein leads to malignant
transformation by interference with
control of proliferation, adherence,
and apoptosis
Biology of CML
Disease progression associated with
chromosomal changes in 50-80% cases
Karyotypic evolution may precede
hematologic and clinical manifestations
Frequent changes are trisomy 8,
isochromosome
i(17q), trisomy 19,
additional Ph chromosome
Alterations in tumor suppressor genes
Detection of BCR-ABL
Cytogenetic analysis
Gold standard
Time-consuming, 20-25
metaphases/sample
Clinical sign
a. Chronic phase
- Splenomegaly
- Hyperkatabolic state
b. Acute Transformation
- as acute leukemia
Laboratory findings:
a. CBC and blood smear : mild anemia, severe leukositosis,
found every spectrum of granulosit series , which the most
dominat is mielosit dan netrofil
b. BM : hyperseluler
* Acute Transformation :
2/3 - mieloid
1/3 - limfoid
Acute Transformation :
a. Fever
b. Splenomegaly >>
c. Anemia >>
d. Respon of treatment was decrease
e. Blast in peripheral blood > 5%,
blast in BM > 30%
CML-Chronic Phase
Survival by Prognostic Group
Management
Chronic phase
Hydroxiurea
Busulfan (Myleran)
Interferon
STI671 (Imatinib mesylate)
Suportive treatment
Blast Crisis
Treat as acute Leukemia
Bone Marrow Transplantation