Haematological

Malignancies
Raymond Man

Content
Introduction
Myeloid

Leukaemia
Lymphoblastic Leukaemia
Lymphoma
Multiple Myeloma
(Myelodysplasia)

HAEMATOLOGICAL
MALIGNANCIES

Haematological
Malignancies
Geographical

Variation

(CLL common in West, but rare in Far

East)

Aetiology of Haematological
Malignancies
Largely
As

Unknown

with most disease, combo of

genetic + environmental that
determine risk.

Inherited Factors
Major

Factor
E.g. Downs Syndrome 20-30x
likely to develop acute
leukaemia)
AML,

CLL, Lymphomas have weak

familial tendency, although
largely unknown predisposing
genes.

Environmental
Chemicals

Benzenes
Drugs

Alkylating agents (esp with Rtx)

Radiation

Increased rates following survivors of

atom bomb explosion in Japan

Environmental
Infection
Infection

Viral Viral

EBV
Herpes

HIV

Burkitt Lymphoma
Kaposis sarcoma
HIV-associated Lymphoma

Bacteria
Bacteria

H. Pylori

Gastric Mucosa B-cell (MALT)

Lymphoma

Protozoa
Protozoa
Malaria

Alter host immunity predisposing to

tumour formation e.g. EBV infection

LEUKAEMIA

Leukaemia
Chronic

vs Acute

Acute usually aggressive

Myeloid

vs Lymphoblastic

Leukaemia
Accumulation

of white cells in:

Bone Marrow
Blood
Cause:

Bone Marrow Failure

Organ Infiltration

ACUTE MYELOID
LEUKAEMIA

Incidence
most

common form of acute

leukaemia in adults
Increasingly common with age
Median onset 65 years.

Diagnosis
>20%

blast cells in blood /

marrow
or

(<20%

blast cells + specific

leukaemia-associated cytogenic
or molecular genetic
abnormalities are present)

Clinical Features
Bone

Marrow Failure

Freq Infections
Anaemia
Thrombocytopenia
Infiltration

Gum hypertrophy
Skin
Brain

Investigations
FBC

WCC
Hb
MCV
Plts

Normochromic
Normocytic
anaemia
Thrombocytopenia

Blood

Film:

Increased WCC
Bone

Marrow
Aspirate
Hypercellular
Leukaemic Blasts

Investigations
To clarify blast cells:
Microscopic

exam

Morphology
Immunophenotypic

Flow cytometry
Cytogenic
Molecular

analysis

Treatment
1.

General Supportive Therapy

2.

Aim of treatment
Induce remission
<5% in bone marrow
Normal blood counts
Clinical status

Eliminate Disease
Allogenic stem cell transplantation
considered in poor prognosis cases or in
relapse

Treatment
3.

Specific Therapy of AML

Different in specific age groups

CHRONIC MYELOID
LEUKAEMIA

Chronic Myeloid
leukaemia
BCR-ABL

1 +ve
Philadelphia Chromosome
(translocate chromosome 9 and 22)
[accounts for 15% of leukaemias]

Clinical Features
Freq

40-60
No predisposing factors
Hypermetabolism
Splenic

enlargement (MASSIVE)
Anaemia
Thrombocytopenia
Hyperuricaemia
(gout/nephropathy)

Investigations
FBC
Leucocytosis (complete spectrum
of myelocytes visible)
Increased Basophils
Normochromic normocytic
anaemia is usual
Uric acid
Cryptogenic

analysis

Treatment
Chemotherapy
Stem

cell transplantation

Allogenic SCT proven curative

(reserved for chemo failures only
due to risk).

Accelerated phase disease

Acute

transformation

(majority

to AML/mixed)

ACUTE
LYMPHOBLASTIC
LEUKAEMIA

Acute Lymphoblastic
Leukaemia
Accumulation

of lymphoblasts

Incidence

Highest at 3-7 years

Second peak at ~ 40
85%

B cell dominance
15% T cell (male predominance)

Pathogenesis
Variable
May

involve:

1st event occurring in utero

2nd postnatally, e.g infx

Clinical Features
Organ Infiltration
Bone

Marrow
Failure:
Anaemia
Neutropenia
Thrombocytopaen
ia

Tender bones
Lymphadenopathy
Hepatosplenomeg
aly
Meningeal
syndrome
Pyrexia
Testicular swelling
(Less common)
Mediastinal
compression (TALL)

Investigations
FBC

Normochromic Normocytic Anaemia

WCC / NAD /
Blood

film

Variable number of blast cells

Bone

Marrow Aspirate

Hypercellular >20% Leukaemic

Blasts

Investigations
LP

not generally done as it may

spread tumour cells

X-rays

lytic bone lesions

Erlarged Thymus

Investigations
Cytogenics
Cytochemistry
Immunological

Tests
Molecular genetics

Treatment
Supportive
Specific

Therapy:

Chemotherapy
Radiotherapy

Factors Guiding Management:

Age
Gender
WCC @ presentation
Evidence base
Type of leukaemia

Treatments
Plan:

Induce remission
Intense dose
CNS directed therapy
Maintenance
(+prophylaxis Ig + abx)

Treatments / Prognosis
90%

cure rates in children

Adults

40% remain leukaemia free

after 5 years
Cure rates in >70yrs <5%
Change in subtypes (Ph+ ALL more
common with age)
Lower dose usage
SCT

CHRONIC LMPHOOID
LEUKAEMIAS

Chronic Lymphoid
Leukaemia
B+T

cells

Generally Incurable
But
Long and fluctuant course
CLL

(Chronic lymphocytic
leukaemia) is the most common of
the Chronic lymphoid leukaemias.

Diagnosis
Chronic

persistent lymphocytosis

B-Cell Disease Clinical

Features
Generally

in older population
Male 2:1 Female
Most are diagnosed on routine bloods
Symmetrical enlarged lymph nodes
(cervical, axillary, inguinal, tonsilar).
Non-tender + discreet
Marrow Failure
Hepatosplenomegaly
Immunosuppressed.

Lymph Node Location

Lab Test
Lymphocytosis
Ig

Monoclonal Banding
Anaemia + Thrombocytopenia
Bone

Marrow aspiration

Staging

Treatment
Cure

is rare in CLL
Mainly Conservative management
Too

early chemo can shorten life

expectancy
Many do not require treatment, but
would be for troublesome:
Organomegaly
Haemolysis
Bone marrow suppression

Treatment
Chemotherapy
Steroid
Radiotherapy
Splenectomy
SCT
Immunoglobulin

replacement

Prognosis
Gradually

become resistant to

chemo
Progression

Extensive bone marrow infiltration

Bulky disease
Recurrent infection
Richters transformation (High grade
Lymphoma)

HODGKIN LYMPHOMA

Hodgkin Lymphoma
Malignant

lymphocytes
Accumulating in lymph nodes
Lymphadenopathy
Occasionally spill into blood
(Leukaemic phase) or infiltrate
organs outside lymphoid tissue

Hodgkin vs Non Hodgkin

Reed-Sternberg

cells

Clinical Features
Painless,

non tender,
asymmetrical, firm, discrete
rubbery enlargement of
superficial lymph nodes.
Splenomegaly
Constitutional symptoms

Investigation
LN

biopsy

Blood

tests
CXR/CT/MRI
Bone Marrow Trephine
Liver Biopsy
PET

Staging

Treatment
Radiotherapy
Chemotherapy
Stem

Cell Transplant?

Prognosis

Late effects of HL +
Treatment
Secondary

cancers
S/E of treatment

Sterility
GI complications
Coronary artery disease
Cardiopulmonary issues

Otherwise excellent prognosis (cure

in 85%)

NON-HODGKIN
LYMPHOMA

Non-Hodgkin Lymphoma
Large

group of clonal lymphoid

tumour
85% B cell origin
Variable

presentation
Irregular spread
Unknown

aetiology (Infectious
agents are important causes in
particular sybtypes)

Classification
T

cell
B cell

Pathophysiology
B

cells mature in lymph nodes

B-cell

lymphoma tend to mimic

normal B cells at different stages
of development:
Pre-curosr B cells
Germinal centres
Post GC cells in lymph nodes

Pathophysiology
T

cells mature in thymus

T-cell

lymphoma resemble:

Precursor T cells in bone marrow or

thymus
Peripheral mature T cells

High Grade vs Low Grade

NHL

= diverse group
Varying progression

Indolent
/
tolerabl
e

Rapid /
fatal
disease

High Grade vs Low Grade

Low

grade respond well to

chemotherapy but are very
difficult to cure

High

grade lymphoma require

aggressive and urgent treatment,
but often curable

Lymphoma vs Leukaemia
Lymphoma

Lymph nodes
spleen
Other solid organs
Leukaemia

Predominant bone marrow

Circulating tumour cells

Lymphoma vs Leukaemia

The differentiation may not be

clear and will depend on
presentation / investigations

NHL Clinical Features

Superficial

lymphadenopathy
Constitutional symptoms
Fever/night sweats/wt loss does not occur as freq as
HL. Sx more ass with disseminated disease
Oropharyngeal

involvement
Bone marrow involvement
Abdominal disease
Hepatosplenomegaly
Abdo lymphadenopathy
Other

organs

Skin
Brain
Testes
Thyroid

Investigation
Lymph

node biopsy
FNA of LN
To exclude other causes (e.g. TB)
FBC

(Marrow involvement)
Marrow Aspiration
Cytogenetics
HIV testing

CXR
PET

/ CT

Staging

Subtypes of Low grade

NHL (B)
Marginal

Zone Lymphomas

MALT, Spleen
Follicular

Lymphoma

Widespread painless lymph nodes

Mantle

Cell Lymphoma

Subtypes of High grade

NHL (B)
Diffuse

Large B Cell Lymphomas

Rapid and affect most organs

Classic
Burkitt

Lymphoma

Typically child - massive lymphadenopathy of

jaw. EBV and HIV
Primary

CNS Lymphoma

Rare, in older patients and HIV. Long term

cognitive dysfunction is an issue
Lymphoblastic

Leukaemia

Children/Young adults. Merge clinically and

morphologically with ALL.

T Cell Lymphoma
Less

common
Mycosis fungoides
Chronic Cutaneous T cell lymphoma
(Pruritis and psoriasis-like lesions).
Peripheral

T Cell NHL

(Post Thymic)
Anaplastic

Large Cell Lymphoma

Common in children

KAHLER'S DISEASE

MYELODYSPLASTIC
SYNDROME