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?