leukaemia & lymphoma

7/30/2019 Leukaemia & Lymphoma

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Leukaemia & Lymphoma

Edward Morris

Consultant Haematologist


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Diagnosis of haematological

malignancies

History

Examination

Investigation


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Full blood count

Hb 140 115-160g/L

MCV 87 80-100 fL

WCC 6.9 4-11 x109/L

Neutrophils 3.4 2-8 x109/L

Lymphocytes 2.6 1-4 x109/L

Eosinophils 0.4


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Blood film


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Bone marrow biopsy


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Bone marrow biopsy


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Lymph node biopsy


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Lymph node biopsy


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Immunophenotyping

CD3

NK1.1


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Immunophenotyping

CD3

Anti-CD3

Fluorochrome

NK1.1


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Immunophenotyping

CD3

Anti-CD3

Fluorochrome

NK1.1

Anti-NK1.1

Different fluorochrome


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Immunophenotyping

CD3

Anti-CD3

Fluorochrome

NK1.1

Anti-NK1.1

Different fluorochrome


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Immunophenotyping

CD3

NK1.1

R2

R3

R4


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Cytogenetics


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FISH / PCR


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Leukaemia

Acute Myeloid Leukaemia (AML)

Acute Lymphoblastic Leukaemia (ALL)

Chronic Myeloid Leukaemia (CML)

Chronic Lymphoblastic Leukaemia (CLL)


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Case 1: 67 year old female

Retired librarian

Tired++ last 3/12

Vague abdominal discomfort


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PMHx

Gastric ulcer aged 55 yrs

Hypertension

Drugs

Atenolol

Allergic to penicillin (widespread rash)


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SHx

Divorced

2 children

Non-smoker

Occasional alcohol


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O/E

Skin and mouth NAD

No lymph nodes

CVS and RS normal

Spleen palpable 8cm below costal margin


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What next?


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Bone marrow biopsy


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Bone marrow biopsy

Large numbers of myeloid precursors

Left-shift but normal maturation

3% myeloblasts (confirmed by flow-

cytometry)


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Cytogenetics


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Diagnosis

Chronic Myeloid Leukaemia (CML)

Chronic phase


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Chronic Myeloid Leukaemia

High WCC & splenomegaly

Frequently incidental finding
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Chronic phase

Accelerated phase

Blast crisis

Chronic Myeloid Leukaemia


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BCR-ABL fusion protein

Tyrosine kinase

Drives uncontrolled cell proliferation


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FISH


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PCR


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Cell Signalling


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Tyrosine kinase


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BCR-ABL

Constitutively phosphorylated tyrosine kinase


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Glivec


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Chronic Lymphocytic

Leukaemia (CLL)

Most common leukaemia in developed countries

Gradual accumulation of B lymphocytes

Generally elderly but 20%


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CLL - Complications

Variable clinical course

B Symptoms

Bone marrow failure

Due to marrow replacement

Auto-immune

Haemolysis, ITP


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CLL - Treatment

Do nothing!

Alkylating agents (eg Chlorambucil)

Combination chemotherapy (eg CVP)

Purine analogues (eg Fludarabine)

Monoclonal antibodies (eg anti-CD52)

Bone marrow transplant


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38 year old female

Works in garden nursery

Sore mouth 3 weeks

Saw GP

1st

visit - reassured

2ndvisit - antibiotics

3rdvisit - FBC performed


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PMHx

Nil of note

Drugs Nil

No known allergies


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SHx

Married

2 children. Well

Non-smoker

Approx 10 units alcohol/week


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O/E

Mouth ulcers

Nil else


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What next?


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Admit TTH Oncology Ward immediately

Blood work-up

Biochemistry

Clotting Virology

Bone marrow biopsy


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Bone marrow biopsy

64% myeloblasts


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Flow cytometry

70% of nucleated cells:

CD13+

CD33+

CD34+


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Cytogenetics

Inv(16)


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Diagnosis

Acute Myeloid Leukaemia

WHO: AML with inv(16)


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FAB Classification


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WHO Classification


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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 ofinfection & bleeding


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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


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Lymphoma


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Lymphoma - Presentation

Lymphadenopathy

Often painless

Extra-nodal disease

Skin, GI tract, bone marrow

B-symptoms

Fever, drenching night sweats, wt loss >10%body weight


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Lymphoma - Diagnosis

Biopsy

Lymph node

Excis ion please!

Other tissue


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Lymphoma - Diagnosis

Staging investigations

CT Scan chest/abdo/pelvis

PET scan

Bone marrow biopsy

(Lumbar puncture)


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Positron Emission

Tomography (PET)

Injection of radio-labelled

glucose

As the isotope undergoes

positron emission decaypositrons are released

Positrons encounter electrons

and produces a pair of gamma

photons moving in opposite

directions

Detected by a scintilator


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Lymphoma - Classification

Hodgkins Lymphoma

Non-Hodgkins Lymphoma


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Hodgkins Lymphoma

Nodular sclerosing

Lymphocyte depleted

Mixed cellularity

Lymphocyte predominant

Classical HD


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Non-Hodgkins Lymphoma

Low grade (Follicular NHL)

Intermediate grade (Mantle Cell)

High grade (Diffuse Large B Cell

Lymphoma)

Very high grade (Burkitts)


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65 year old male

Retired construction worker

Sore left shoulder (after throwing

lawnmower into skip)

Previous rotator cuff repair


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Seen by orthopaedic team

Large lymph node left supra-clavicular region


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What next?


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Histological diagnosis

Diffuse large B cell lymphoma


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Presenting complaint

Pain left shoulder 4 weeks

Swelling above clavicle 3 weeks

Drenching night sweats 3 weeks

12kg weight loss


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PMHx

Type 2 diabetes (diet controlled)

Drugs Panadol for pain

Viagra prn

No known allergies


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SHx

Married

4 children. Well

Non-smoker

No alcohol


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O/E

Extensive soft tissue swelling over leftshoulder

Unhealed wound over biopsy site

2cm lymph node left axilla

Bilateral inguinal lymph nodes (1-2cm)


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What next?

Complete staging: CT + PET


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Complete staging: CT + PET


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Bone marrow Biopsy:

Normal

Serum LDH:

170


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Staging


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Diagnosis

Diffuse large B cell NHL

Stage IIIB


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International Prognostic Index

Age >60 years

LDH > normal

WHO performance status 2-4

Stage III and IV

Extra-nodal involvement >1 site


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Score Risk 5 yr survival

0-1 Low 70%

2 Low intermediate 50%

3 High intermediate 40%

4-5 High 30%


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>60 yrs 1

2/5

Low intermediate

risk

High LDH 0WHO PS 0 0

Stage 3 1

1 extra-nodal site 0

NHL T t t


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NHL - Treatment

High Grade

Stage 1A

Short course chemotherapy, monoclonal

antibodies & IFRT

Good prognosis

NHL T t t


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NHL - Treatment

High Grade

Stages 2-4

Combination chemotherapy + monoclonal

antibodies

? role IF radiotherapy

R-CHOP 14

NHL Treatment


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NHL - Treatment

Monoclonal antibodies

Rituximab (Mabthera)

NHL Treatment


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NHL - Treatment

Conclusions


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Conclusions

A wide range of malignancies arise fromhaematological precursors

Diagnosis and staging critical

Treatment

Prognosis

Range from indolent to very aggressive

Rapidly expanding range of treatmentsincluding designer drugs and stem celltransplantation


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Any questions?

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