DrMaysem Mouayad Alwash LEC3 Objectives 1Define CLL 2Enumerate the clinical features of CLL 3Describe the laboratory diagnosis of CLL 4Know the staging system and prognostic factors ID: 928538
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Slide1
Chronic Leukemias
Assistant Prof:Dr.Maysem Mouayad Alwash LEC.3
Slide2Objectives:1-Define CLL 2-Enumerate the clinical features of CLL3-Describe the laboratory diagnosis of CLL4-Know the staging system and prognostic factors
5-Define CML6- Enumerate the clinical features of CML7-Describe the laboratory diagnosis of CML8-Describe Philadelphia chromosome.
Slide3The chronic lymphoid leukaemiasSeveral disorders are included in this group and are characterized by accumulation in the blood of mature lymphocytes of either B‐ or T‐cell type Subtypes are distinguished by morphology,
immunophenotype and genetic analysis. This group is characterized by a chronic persistent lymphocytosis.
Slide4Classification of the chronic lymphoid leukaemias
.
B
‐
cell
T
‐
cell
Chronic lymphocytic
leukaemia
(CLL)Large granular lymphocytic leukaemiaProlymphocytic leukaemia(PLL)T‐cell prolymphocytic leukaemia (T‐PLL)Hairy cell leukaemia (HCL)Adult T‐cell leukaemia/ lymphomaPlasma cell leukaemia
Slide5Chronic lymphocytic leukaemiaChronic lymphocytic leukaemias are characterized by the
accumulation of mature B or T lymphocytes in the blood.
Individual
subtypes are distinguished on the basis of
morphology,
immunophenotype
and
cytogenetics
.
Slide6Chronic lymphocytic leukaemia (CLL, B cell): -It
is the most common of the chronic lymphoid leukaemias
,
has
a peak
incidence
between
60 and 80 years of age.
-There is genetic predisposition to development of the disease.
Slide7Clinical features:1-It is more common in men than women-Most of cases (Over 80%) are diagnosed incidently
from the results of a routine blood test, usually taken for another reason.3-Enlargement of cervical, axillary or inguinal lymph nodes is the most frequent clinical sign The nodes are usually discrete and non‐tender.
Slide8bilateral cervicallymphadenopathy in a 67‐year‐old woman.
Slide94 .Features of anaemia may be present and patients with thrombocytopenia may show bruising or purpura.
5 .Splenomegaly and, , hepatomegaly are common in later stages.
Slide106 Immunosuppression is often a significant problem resulting from hypogammaglobulinaemia
and cellular immune dysfunction.
Slide11Early in the disease course bacterial infections, such as sinus and chest infections, predominate but with advanced disease viral infections, especially herpes zoster , and fungal infections are also seen.
Slide12Chronic lymphocytic leukaemia: herpes zoster infection in a 68‐year‐old female.
Slide137. The disease may also transform into a condition resemble high‐grade lymphoma ,known as (Richter s transformation)
Slide14Laboratory findings:1. Lymphocytosis. The absolute clonal B cell lymphocyte count is more than
>5 × 109/L.
Slide15Most of these cells in the blood film appear as small lymphocytes. These cells are more fragile than normal , leading to the formation of characteristic ' smear' or ‘'Smudge cells' when blood film is spread
Slide16peripheral blood film showing lymphocytes with thin rims of cytoplasm, coarse condensed nuclear chromatin and rare nucleoli. Typical smudge cells are present.
Slide17CLL
Slide182.Normochromic normocytic anaemia is present in later stages as a result of marrow infiltration or
hypersplenism. Autoimmune haemolysis
may also
occur
.
Slide193.Thrombocytopenia occurs in many patients and may also have an autoimmune basis.4. Bone marrow aspiration
shows lymphocytic replacement of normal marrow elements .
Slide205 Reduced concentrations of serum immunoglobulins
(normal immunoglobulins
)
and
this becomes more marked with advanced disease.
Slide216. Autoimmunity directed against cells of the haemopoietic
system is common. Autoimmune haemolytic
anaemia
is most frequent but immune thrombocytopenia, neutropenia and red cell aplasia are also seen.
Slide227.Immunophenotyping (usually done by flowcytometry) of the lymphocytes is important to confirm the diagnosis of CLL, since on the bases of clinical and haematological
features confusion with non-Hodgkin lymphoma can occur.
Slide23Immunophenotyping also provides information useful in indicating prognosis .Expression of CD38 , ZAP70 are associated with a worse prognosis.
-Specific cytogenetic abnormalities (detected by FISH) can also give prognostic information.
Slide24Staging:It is useful to stage patients at presentation both for prognosis and for deciding on therapy.
The re are two important staging system : Rai and
Binet
staging
systems .
.
Slide25Slide26Case Study A 75 year –old- man, during a routine check up has been found to have a WBC count of ,18 x 10 9 , lymphocyte count 12.3 x 10 9 ,Hb 9 g/dl ,low platelet count . Blood film shows mature small lymphocytes with many smear cells .Q1/What is the most likely diagnosis?
Q2/What is the stage of disease ?Q3/ What are the possible causes of his low haemoglobin level?Q4/ Is this patient at risk of infection? Why ?
Slide27@@@Less common subtypes of chronic lymphoid leukaemias include prolymphocytic leukaemia, hairy cell leukaemia
and T‐cell disorders
Slide28Chronic myeloid leukaemiaIt is a clonal disorder of a pluripotent stem cells. The disease can occur at any age but is most common between the ages of 40 and 60 years( It is largely a disease of adults).
Slide29This leukaemia results from a specific chromosomal translocation ,desined
t(9;22), between one chromosome 9 and one chromosome 22 that leads to formation of an oncogenic fusion gene ,
BCR-ABL1
,on the abnormal chromosome 22
.
Slide30The abnormal chromosome 22 is refered to as Philadelphia (Ph) chromosome . The resulting
chimeric BCR‐ABL1 gene codes for a fusion protein with increased tyrosine kinase activity.
Slide31Philadelphia chromosome
Slide32Slide33Clinical featuresIn up to 50% of cases the diagnosis is made incidentally from a routine blood count.
In those cases where the disease presents clinically, the following features may be seen:1-Symptoms related to hypermetabolism
(e.g. weight loss, lassitude, anorexia or night sweats).
Slide341 .2. Splenomegaly is
nearly always present and may be massive.3 .Features of anaemia
may include pallor,
dyspnoea
and tachycardia.
4. Bruising,
epistaxis
,
menorrhagia
or
haemorrhage from other sites because of abnormal platelet function.5 .Gout or renal impairment caused by hyperuricaemia from excessive purine breakdown
Slide35Laboratory findings1. Leucocytosis: marked increase in WBC count .
A complete spectrum of myeloid cells is seen in the peripheral blood. The levels of neutrophils and myelocytes exceed those of blast cells and
promyelocytes
.
Slide36CML
Slide37CML
Slide38CML
Slide392. Increased circulating basophils are a characteristic feature.3.Increased
circulating eosinophiles4.Normochromic normocytic
anaemia
is usual.
5.
Platelet
count
may be
increased
(most frequently),
normal or decreased.
Slide406 Bone marrow is hypercellular with granulopoietic predominance.7.Serum uric acid
is usually raised. 8. Confirmation of the diagnosis requires cytogenetic analysis
looking for t(9,22) and
molecular or FISH analysis to demonstrate the BCR-ABL1 fusion gene.
Slide41FISH
Slide42Natural history:The natural history of untreated CML is triphasic:1.Chronic
phase:The majority of patients are diagnosed in CMLchronic phase.
.
Slide432. Accelerated phase: in the peripheral blood there is thrombocytopenia or refractory thrombocytosis ,increased basophils and may be some increase in blast cells.
Slide443.Blastic crisis: greater than 20% blasts in blood or marrow,it may emerge suddenly from chronic phase or may follow an accelerated phase.Blastic
crises may be lymphoblastic , myeloid or mixed
Slide45CASEA 46-YEAR –old – woman presents with fever , sweating ,weight loss .On examination she was found to have massive splenomegally . Her blood count shows: WBC 98 x 10 9 , Hb 8 g/dl ,platelet count 504 x 10 9
. A blood film shows many white blood cells precursors particularly myelocytes , incraesed numbers of
neutrophils
,
eosinophils
and
basophils
Q1/What is the most likely diagnosis?
Q2/What test will be of benefit to confirm diagnosis?
Slide46