Leukaemia & Lymphoma
Edward Morris Consultant Haematologist
Diagnosis of haematological malignancies
History
Examination
Investigation
Full blood count
Hb
MCV WCC Neutrophils Lymphocytes Eosinophils
140
87 6.9 3.4 2.6 0.4
115-160g/L
80-100 fL 4-11 x109/L 2-8 x109/L 1-4 x109/L <0.6 x109/L
Basophils
Others Plts
0.1
0.0 394
<0.2 x109/L
0 x109/L 140-400 x109/L
Blood film
Bone marrow biopsy
Bone marrow biopsy
Lymph node biopsy
Lymph node biopsy
Immunophenotyping
CD3 NK1.1
Immunophenotyping
Anti-CD3
CD3 NK1.1
Fluorochrome
Immunophenotyping
Anti-CD3
CD3 NK1.1 Anti-NK1.1
Fluorochrome
Different fluorochrome
Immunophenotyping
Anti-CD3
CD3 NK1.1 Anti-NK1.1
Fluorochrome
Different fluorochrome
Immunophenotyping
Gp 1 CD3 Neg PE NK1.1 .001
R2
NK1.1
R3
R4 100 101 10 CD3 CD3 FITC 2 103 104
Cytogenetics
FISH / PCR
Leukaemia
Acute Myeloid Leukaemia (AML) Acute Lymphoblastic Leukaemia (ALL) Chronic Myeloid Leukaemia (CML) Chronic Lymphoblastic Leukaemia (CLL)
Case 1: 67 year old female
Retired librarian
Tired++ last 3/12 Vague abdominal discomfort
PMHx
Gastric ulcer aged 55 yrs Hypertension
Drugs
Atenolol
Allergic to penicillin (widespread rash)
SHx
Divorced 2 children
Non-smoker
Occasional alcohol
O/E
Skin and mouth NAD
No lymph nodes CVS and RS normal
Spleen palpable 8cm below costal margin
What next?
Bone marrow biopsy
Bone marrow biopsy
Large numbers of myeloid precursors
Left-shift but normal maturation 3% myeloblasts (confirmed by flowcytometry)
Cytogenetics
Diagnosis
Chronic Myeloid Leukaemia (CML) Chronic phase
Chronic Myeloid Leukaemia
High WCC & splenomegaly Frequently incidental finding
Chronic Myeloid Leukaemia
Chronic phase
Accelerated phase
Blast crisis
BCR-ABL fusion protein Tyrosine kinase Drives uncontrolled cell proliferation
FISH
PCR
Cell Signalling
Tyrosine kinase
BCR-ABL
Constitutively phosphorylated tyrosine kinase
Glivec
Chronic Lymphocytic Leukaemia (CLL)
Most common leukaemia in developed countries Gradual accumulation of B lymphocytes
Generally elderly but 20% <55yrs
CLL - Complications
Variable clinical course
B Symptoms
Bone marrow failure
Due to marrow replacement
Auto-immune
Haemolysis, ITP
CLL - Treatment
Do nothing!
Alkylating agents (eg Chlorambucil)
Combination chemotherapy (eg CVP)
Purine analogues (eg Fludarabine)
Monoclonal antibodies (eg anti-CD52) Bone marrow transplant
38 year old female
Works in garden nursery Sore mouth 3 weeks
Saw GP
1st visit - reassured 2nd visit - antibiotics 3rd visit - FBC performed
PMHx
Nil of note
Drugs
Nil
No known allergies
SHx
Married 2 children. Well
Non-smoker
Approx 10 units alcohol/week
O/E
Mouth ulcers Nil else
What next?
Admit TTH Oncology Ward immediately
Blood work-up
Biochemistry Clotting Virology
Bone marrow biopsy
Bone marrow biopsy
64% myeloblasts
Flow cytometry
70% of nucleated cells:
CD13+ CD33+ CD34+
Cytogenetics
Inv(16)
Diagnosis
Acute Myeloid Leukaemia
WHO: AML with inv(16)
FAB Classification
WHO Classification
Acute Leukaemia - Treatment
Intensive chemotherapy Multiple cycles over many months Regimens constantly evolving
Majority of patients in clinical trials
Severe bone marrow suppression
Significant risks of infection & bleeding
Acute Leukaemia
Well. Working full time. 2 young children
Sore mouth
AML
6 months intensive chemo (+ ? stem cell transplant)
20% chance dying from chemo 50% chance long term cure
Lymphoma
Lymphoma - Presentation
Lymphadenopathy
Often painless
Extra-nodal disease
Skin, GI tract, bone marrow
B-symptoms
Fever, drenching night sweats, wt loss >10% body weight
Lymphoma - Diagnosis
Biopsy
Lymph node
Excision please!
Other tissue
Lymphoma - Diagnosis
Staging investigations
CT Scan chest/abdo/pelvis PET scan Bone marrow biopsy (Lumbar puncture)
Positron Emission Tomography (PET)
Injection of radio-labelled glucose As the isotope undergoes positron emission decay positrons are released Positrons encounter electrons and produces a pair of gamma photons moving in opposite directions Detected by a scintilator
Lymphoma - Classification
Hodgkins Lymphoma
Non-Hodgkins Lymphoma
Lymphoma - Classification
Hodgkins Lymphoma
Nodular sclerosing Lymphocyte depleted Mixed cellularity Lymphocyte predominant
Classical HD
Lymphoma - Classification
Non-Hodgkins Lymphoma
Low grade (Follicular NHL) Intermediate grade (Mantle Cell) High grade (Diffuse Large B Cell Lymphoma)
Very high grade (Burkitts)
65 year old male
Retired construction worker
Sore left shoulder (after throwing lawnmower into skip) Previous rotator cuff repair
Seen by orthopaedic team Large lymph node left supraclavicular region
What next?
Histological diagnosis
Diffuse large B cell lymphoma
Presenting complaint
Pain left shoulder 4 weeks
Swelling above clavicle 3 weeks
Drenching night sweats 3 weeks 12kg weight loss
PMHx
Type 2 diabetes (diet controlled)
Drugs
Panadol for pain
Viagra prn No known allergies
SHx
Married 4 children. Well Non-smoker No alcohol
O/E
Extensive soft tissue swelling over left shoulder Unhealed wound over biopsy site 2cm lymph node left axilla Bilateral inguinal lymph nodes (1-2cm)
What next?
Complete staging: CT + PET
Bone marrow Biopsy: Normal
Serum LDH: 170
Staging
Diagnosis
Diffuse large B cell NHL
Stage IIIB
International Prognostic Index
Age >60 years LDH > normal WHO performance status 2-4 Stage III and IV Extra-nodal involvement >1 site
International Prognostic Index
Score 0-1 2 3 4-5 Risk Low Low intermediate High intermediate High 5 yr survival 70% 50% 40% 30%
International Prognostic Index
>60 yrs
High LDH
WHO PS 0 Stage 3 1 extra-nodal site
0
0 1 0
2/5 Low intermediate risk
NHL - Treatment
High Grade
Stage 1A
Short course chemotherapy, monoclonal antibodies & IFRT Good prognosis
NHL - Treatment
High Grade
Stages 2-4
Combination chemotherapy + monoclonal antibodies ? role IF radiotherapy R-CHOP 14
NHL - Treatment
Monoclonal antibodies
Rituximab (Mabthera)
NHL - Treatment
Conclusions
A wide range of malignancies arise from haematological precursors Diagnosis and staging critical
Treatment Prognosis
Range from indolent to very aggressive Rapidly expanding range of treatments including designer drugs and stem cell transplantation
Any questions?
