CLL Flashcards
What?
Accumulation of mature B cells that have escaped apoptosis and undergone cell-cycle arrests in G0/G1 phase in blood, BM, spleen, LN and liver
Morphologically normal but immature and nonreactive -> immunological compromise
Epidemiology
Most common leukaemia
Disease of older people - median age at diagnosis 72
Strong familial RF, but genetic basis largely unknown
Mutations, trisomies and deletions influence risk
Pneumonia may be a triggering event
Rai stages + median survival
0 - Lymphocytosis alone - >13 years
I - Lymphocytosis + lymphadenopathy - 8 years
II - Lymphocytosis + spleno- or hepatomegaly - 5 years
III - Lymphocytosis + anaemia (Hb <11) - 2 years
IV - Lymphocytosis + platelets <100 - 1 year
Binet stages
Stage A: Hb >10; platelets >100; <3 LN areas involved
Stage B: Hb >10; platelets >100; 3+ LN areas involved
Stage C: Hb <10; platelets <100 or both
Presentation
Insidious onset, often asymptomatic, picked up at routine blood test
Anorexia, weight loss
Infections (pneumonia, herpes simplex/zoster)
Bleeding or petechiae (thrombocytopenia)
Abdominal discomfort (splenomegaly)
Symmetrically enlarged, rubbery, non-tender LN - local or generalise
Tiredness, fatigue, pallor (anaemia)
Splenomegaly, hepatolmegaly
Skin infiltration (rare); involvement of lacrimal and salivary glands is rare
Tonsillary enlargement
Investigations - bloods
FBC: B cell lymphocytosis; normocytic, normochromic anaemia
Peripheral blood smear: lymphocytosis; smudge/smear cells
Direct antiglobulin test (DAT), aka Coomb’s test: in all anaemic patients and prior to starting treatment - to identify autoimmune related haemolytic anaemias
BM aspirate: lymphocytic replacement of normal marrow. Not always necessary but can help diagnosis and assess complications eg is thrombocytopenia/anaemia due to BM infiltration or splenic destruction
LN biopsy: required if LN enlarge rapidly - assess possibility of transformation to high-grade lymphoma. Transformation + fever, weight loss and pain = Richter’s syndrome.
Immunophenotyping (peripheral blood): MOST VALUABLE to confirm CLL and show clonal B cells expressing Ags
Ig levels if repeated infection
Cytogenetics not usually performed
Test for deletion of TP53, a tumour suppressor gene - deletion is associated with lower response and survival
CMV, HCV, HBV status - prior to chemo or SCT
Imaging: not really done - diagnosis is on clinical and bloods; can scan organs for megaly or CT CAP may show urological or respiratory obstruction due to LNs
Management - general principles
No curative treatment, but can treat disease
Early disease: watch and wait (no advantage to early treatment); blood cell counts and clinical examination every 3-12 months
Active symptomatic disease = weight loss >10%, extreme fatigue, fever, night sweat, progressive marrow failure, autoimmune anaemia or thrombocytopenia not responding to pred, progressive splenomegaly, massive lymphadenopathy or progressive lymphocytosis (increase >50% in 2 months/doubling time <6 months): chemotherapy
Antibiotic prophylaxis, flu, Hib and pneumoccal vaccine and varicella-zoster Ig for those at risk of infection
Management - chemotherapy
1) Alkylating agents eg Bendamustine
2) Purine analogues eg Fludarabine
3) Monoclonal antibodies eg Rituximab, alemtuzumab
4) Steroids - for autoimmune complications, to improve BM function prior to chemo, to treat CLL that has not responded to standard treatment
Management - non-chemo
1) SCT - curative, but majority of patients are elderly and there is high morbidity and mortality. Good for younger patients with adverse prognostic factors
2) Surgery - splenomegaly and pancytopenia: splenectomy - significant improvement in Hb and platelets. Must immunise with pneumococcal, meningococcal and Hib vaccines at least a week before op
3) Radiotherapy - palliative for spleen, or for bulky nodal masses
Complications
Autoimmune haemolysis
Increased infection (both due to disease and treatment) due to hypogammaglobulinaemia (bacterial and viral, ezp zoster), neutropenia, inpaired Tcell, NKcells and complement function
Marrow failure
Hyperviscosity syndrome - CNS or resp system - urgent pred and chemo and uric acid nephropathy
Lymphomatous transformation - Richter’s syndrome
Secondary malignancies incl MDS, AML and solid tumours
Prognosis
1/3 never progress; 1/3 progress slowly and 1/3 progress actively
May have initial ‘benign’ course followed by a terminal and resistant phase
Depends on stage
Younger patients more like to die of CLL-related causes, older more commonly die of unrelated causes
Poor prognosis: cytogenetic abnormalities
Death often due to infection (pneumococcus, haemophilus, meningococcus, Candida or aspergillosis) or transformation to aggressive lymphoma
