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Презентация на тему Chronic lymphocytic leukemia

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2. CHRONIC LYMPHATIC LEUKEMIA Definition: CLL is a
3. CLL - EPIDEMIOLOGYMost common leukemia of Western
4. CLL – ETIOLOGY The cause of CLL
5. PATHOPHYSIOLOGY
6. CLL – INITIAL SYMPTOMSApproximately 40% are asymptomatic
7. CLL – LAB FINDINGS a) Blood test
9. CLL - LABORATORY FINDINGS (2)Clonal expansion of
10. CLL - IMMUNOPHENOTYPEDetect antigens on surface of
11. CLL – RAI STAGING SYSTEM
13. CLL – BINET STAGING SYSTEM
15. CLL – TREATMENT (1)Watch and waitMonotherapyglucocorticoidsalkylating agents
16. CLL – TREATMENT (2)Hematopoietic stem cell transplantationallogeneic
18. CLL – TREATMENT STRATEGY
19. CLL - COMPLICATIONSSevere systemic infectionsBleedingRichter’s transformationProlymphocytoid transformationSecondary malignanciesAcute myeloid leukemia
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CHRONIC LYMPHATIC LEUKEMIA Definition: CLL is a neoplastic disease characterized by proliferation and accumulation (blood, marrow and lymphoid organs) of morphologically mature but immunologically dysfunctional lymphocytes

CLL - EPIDEMIOLOGYMost common leukemia of Western world.Less frequent in Asia and

CLL – ETIOLOGY The cause of CLL is unknownThere is increased incidence

CLL – INITIAL SYMPTOMSApproximately 40% are asymptomatic at diagnosis – discovered by

CLL – LAB FINDINGS a) Blood test lymphocytosis ≥ 5G/l (4

CLL - LABORATORY FINDINGS (2)Clonal expansion of B (99%) or T(1%) lymphocyteIn

CLL - IMMUNOPHENOTYPEDetect antigens on surface of cells Specific antibodiesUse flow cytometry

CLL – TREATMENT (1)Watch and waitMonotherapyglucocorticoidsalkylating agents (Chlorambucil, Cyclophosphamide)purine analogues (Fludarabine, Cladribine,

CLL – TREATMENT (2)Hematopoietic stem cell transplantationallogeneic with reduced intesity conditioningautologousNew and

CLL - COMPLICATIONSSevere systemic infectionsBleedingRichter’s transformationProlymphocytoid transformationSecondary malignanciesAcute myeloid leukemia

DIFFERENTIAL DIAGNOSISА) With malignant well-differentiated lymphocytic lymphoma (LS): chronic lymphocytic leukemia is

Слайды презентации

Слайд 2 CHRONIC LYMPHATIC LEUKEMIA
Definition:
CLL is a neoplastic disease

CHRONIC LYMPHATIC LEUKEMIA Definition: CLL is a neoplastic disease characterized by

characterized by proliferation and accumulation (blood, marrow and lymphoid

organs) of morphologically mature but immunologically dysfunctional lymphocytes

Слайд 3 CLL - EPIDEMIOLOGY
Most common leukemia of Western world.
Less

CLL - EPIDEMIOLOGYMost common leukemia of Western world.Less frequent in Asia

frequent in Asia and Latin America.
Male to female ratio

is 2:1.
Median age at diagnosis is 65-70 years.
Uncommon (10%) in patients under 50 years
In US population incidence is similar in different races.

Слайд 4 CLL – ETIOLOGY
The cause of CLL is

CLL – ETIOLOGY The cause of CLL is unknownThere is increased

unknown
There is increased incidence in farmers, rubber manufacturing workers,

asbestos workers, and tire repair workers
Genetic factors have been postulated to play a role in high incidence of CLL in some families

Cytogenetics
clonal chromosomal abnormalities are detected in approximately 50% of CLL patients
the most common clonal abnormalities are:
trisomy 12
structural abnormalities of chromosomes 13, 14 and 11
patients with abnormal karyotypes have a worse prognosis
Oncogenes
in most cases of CLL is overexpressed the proto-oncogene c-fgr 9a member of the src gene family of tyrosine kinases

Слайд 5 PATHOPHYSIOLOGY

Слайд 6 CLL – INITIAL SYMPTOMS
Approximately 40% are asymptomatic at

CLL – INITIAL SYMPTOMSApproximately 40% are asymptomatic at diagnosis – discovered

diagnosis – discovered by a CBC
In symptomatic cases the

most common complaint is fatigue
Well’s syndrome – increase sensitivity to insects bites
B symptoms – fever, sweats, weight loss
Less often the initial complaint are enlarged nodes or the development of an infection (bacterial)
CLL - Clinical findings
Most symptomatic patients have enlarged lymph nodes (more commonly cervical and supraclavicular) and splenomegaly
The lymph nodes are usually discrete, freely movable, and nontender
Hepatomegaly may occure
Less common manifestation are infiltration of tonsils, mesenteric or retroperitoneal lymphadenopathy, and skin infiltration
Patients rarely present with features of anemia, and bruising or bleeding

Слайд 7 CLL – LAB FINDINGS
a) Blood test

lymphocytosis ≥ 5G/l (4 weeks)
b) Morphology monoconal population of small

mature lymphocyte
c) B-cell CLL phenotype clonal CD5+/CD19+ population
of lymphocyte
d) Markers of clonality κ/λ light chain restriction; cytogenetical abnormalities
e) Bone marrow infiltrate > 30% of nuceated cells on aspirate
f) Lymph node diffuse infiltrate of small lymphocye

Слайд 8

Слайд 9 CLL - LABORATORY FINDINGS (2)
Clonal expansion of B

CLL - LABORATORY FINDINGS (2)Clonal expansion of B (99%) or T(1%)

(99%) or T(1%) lymphocyte
In B-cell CLL clonality is confirmed

by
the expression of either  or  light chains on the cell surface membrane
the presence of unique idiotypic specificities on the immunoglobulins produced by CLL cells
by immunoglobulin gene rearrangements
typical B-cell CLL are unique in being CD19+ and CD5+

Слайд 10 CLL - IMMUNOPHENOTYPE
Detect antigens on surface of cells

CLL - IMMUNOPHENOTYPEDetect antigens on surface of cells Specific antibodiesUse flow

Specific antibodies
Use flow cytometry or immunohistochemistry
CLL = mature B

cells
CD5
CD19
CD20 - low
CD22 - low
CD23
Light chains (κ, λ)

Слайд 11 CLL – RAI STAGING SYSTEM

Слайд 12

Слайд 13 CLL – BINET STAGING SYSTEM

Слайд 14

Слайд 15 CLL – TREATMENT (1)
Watch and wait
Monotherapy
glucocorticoids
alkylating agents (Chlorambucil,

Cyclophosphamide)
purine analogues (Fludarabine, Cladribine, Pentostatin)
Combination chemotherapy
Chlorambucil/ Cyclophosphamide + Prednisone
Fludarabine

+ Cyclophosphamide +/- Mitoxantrone
CVP, CHOP
Monoclonal antibodies (monotherapy and in combination)
Alemtuzumab (anti-CD52)
Rituximab (anti-CD20)
Splenectomy
Radiotherapy

Слайд 16 CLL – TREATMENT (2)
Hematopoietic stem cell transplantation
allogeneic with

CLL – TREATMENT (2)Hematopoietic stem cell transplantationallogeneic with reduced intesity conditioningautologousNew

reduced intesity conditioning
autologous
New and novel agents
Oblimersen – bcl2-directed antisense

oligonucleotide
Lenalidomide
Flavopiridol
Anti-CD23
Anti-CD40
Vaccine strategies
Supportive therapy (allopurinol, G-CSF, blood and platelet transfusion, immunoglobulins, antibiotics)