Chronic lymphocytic leukaemia Flashcards
What is CLL
Type of blood cancer occurs due to monoclonal proliferation of B lymphocytes
Who gets CLL
Older adults
Exceedingly rare in children
More common in men
Causative factors
Cause unknown but more likely if:
Deletion in chromosome 13 can be 11 or 17 too
FH - 6-9x risk if first degree family had
Immunity - HIV/AIDS 3x likely
Pathophysiology of CLL
CD5+, CD23+ clonally expand, low surface IgGs
-> accumulation lymphocytes bone marrow -> lymph nodes and other lymphoid tissues
Main mechanisms of CLL
Deletion of chromosome
Hypogammaglobinaemia and haematopoieses
Transformation to aggressive forms
Genetic changes in CLL
13q chromosome deletion 50^
deletions at 11q, 17p (p53 tumour supressor) chromosomes
What is 17q deletion CLL ass with
p53 tumour supressor gene inactivated
Rapid progression, short remission, decreased overall survival
What haem disorders are people with CLL more likely to get
AI haemolytic anaemias
AI thrombocytopenia
What can CLL transfomr to
B cell pro lymphocytic leukaemia -> non hodgkin lymphoma
What is richters transformation
Richters transformetion = CLL -> diffuse large B cell lymphoma
Clinical features CLL
Often asymptomatic esp in early stages
Symmetrical enlarged lymph nodes
hepatomegaly/splenomegaly
Anaemia - tired
Recurrent infections as low Igs
Bleed/brusie - TO
Signs that CLL is active
B cell symptoms
Frequent sev night sweats
Unezplained weight loss >10% BW in last 6 months
High fever absence infection >38
Investigating CLL what do
FBC
Reticulocyte count
Direct antiglobulin test - DAT
immunophenotype
Biochem and serum IgGs
Peripheral blood smear
What do lymphocytes do in CLL
> 5000 B lymphcytes/uL - lymphocytosis
What test confirms CLL
Immunophenotyping of lymphocytes
How confrim lymphocytosis
Peipheral blood smear
Small lymphcytes - scant cytoplasm and nuclei w clumped chromatic
Smudge cells
What are smudge cells
Artefacts from damaged lymphocytes in slide prep as so fragile
What cells are suggestive of CLL on smear
Smudge cells
What genetic test should be performed on all patients before treatment with CLL
Detect TP53 gene
Adverse prognosis if deleted
Determines treatment
Additional investigaitons for CLL
Bone marrow aspiration and biopsy - before therapy as baseline
DAT/coombs test - in all anaemic patients and before commencing therapy
Imaging - CT scan chest abdo pelvis - uropathy or AW obstruction from lymph node compression on organ or structures
What do DAT/coombs test for
All anaemic patients and before commencing therapy look for AI related haemolytic anaemia
Mantle lymphoma vs CLL
Mantly lymphoma doesnt express CD23 antigen
Marginal zone lymphoma vs CLL
similar presentation and immunophenotype as CLL, but typically has a bright surface immunoglobulin and CD20, and bone marrow examination often reveals lymphocytes with notched nuclei.
How tell B cell pro-lymphocytic leukaemia from CLL
> 55% prolymphocytes CD5 negative circulating cells
What staging is used for CLL
Binet staging
Stage A of CLL
> 10g/dL Hb, platelets at least 100x109/L, < 3 lymph node areas invovled
Stage B CLL
Stage A but >3 lymoh node areas involved
Stage C CLL
Hb <10g/dL
PLatelets <100x109 or both
What is one are of lymph nodes
Lymphadenopathy in one area of body irrelevant of if one or both sides
Strategy w early CLL
Watch and wait - regularly monitor
Indicaitons for chemotherapy in CLL
Evidence progressive marrow failure
Massive or progressive or symptomatic splenomegaly or lymphadenopathy
Progressive lymphocytosis >50% increase 2 months
Lymphocyte doubling time <6 months
AI anemia or TP not repsonding to prednisolone
ONe or more of CLL related smyptoms
CLL related symptoms indicating treatment
Night sweats
High fever
Extreme fatigue
Unintentional weight loss >10%
Initial therapy for CLL without Tp53 deletion
Fludarabine
Cyclophosphamide
Rituximab
FCR
First line treatment CLL if FCR not appropriate
Bendamistine
For Stage B/C
3rd option for treatment CLL if dont tolerate other two
Obinutuzumab combo w chlorambucil
What use in Tp53 mutations CLL
Ibrutinib
Alemtuzumab
What treat AI cytopenia with
Corticosteroids
Why are steroids sometimes given before chemo
Improve bone marrow function where theres significant bone marrow infiltration
Relapsed vs refractory CLL
Relapse - Disease responded to therapy but after 6 > months stopped responding
Refractory - doesnt result in remission but more be stable or gets worse within 6 months last treatment
Curative treatmetn CLL
HSCT
Complications CLL
Infection - defctive complement, t cell dysunction, low neutrophils
Anaemia incl AI haemolytic - warm antibody type
Transformation to other lymphoma
Hyperviscosity syndrome
Malignancies - higher risk seconadry
Richters sydnrome symtpoms
Sudden and dramatic increase in size of lymph nodes in neck, axilla, abdo (spleen) or groin
Drmatic unexplained weight loss gever and night sweats
Clinical features hyperviscosity syndorme
Extremely high WCC ->
Altered CNS function/resp insufficiency
Headahce, dizzy, vertiy=go, hearing loss, visual disturb, nystagmus
Most common secondary malginancies risk higher w CLL
Melanoma, soft tissue sarcoma, colorectal cancer, lung cancer, SCC, BCC
Risk factors for worse prognosis CLL
Older
Men
Tp52 and 17p dletion
Trisomy 12
Lymphocyte doubling time < 12 months
Diagnosis at later stage
What features mean survival >10 years
Lymphocytosis only in CLL
What intermediate features mena survival of around 7 years
Lymphadenopathy, hepatomegaly or splenomegaly + lymphocytosis
What parameters mean survival likely <4 years w CLL
Hb <110
Platelets <100,000/mm3
Normal bone marrow what made up of
50% fat
50% cellular acitivty
What makes a leukaemia acute vs chronic
Acute - arrested before differentation eg blasts
Chronic - mature cell mutation