Haematological Malignancies

Sarah Lawrence and Oscar Swift

 Brief overview of the haematological system
 Leukaemias
 Lymphomas
 Myelomas and other paraproteinaemias
 SBAs

 Patients present with pancytopaenia
 Symptoms of anaemia
 Infections
 Bleeding
 NB AML M3 presents with DIC!
 Diagnosis to death 6-12 weeks if untreated
 Chemosensitive
 Best initial test is blood smear
 Blast cells present
 WCC can be low, normal or high

 Patients present more insidiously
 SBA tip – if patient presents at a ‘routine check-up’
answer is much more likely to be chronic leukaemia
 Less likely to present with pancytopaenia
 Diagnosis to death 6-12 years if untreated
 Less chemosensitive
 Best initial test is full blood count
 WCC always high
 Look at white cell differential
 ‘Smudge’ cells in CLL on smear

Classification of leukaemia
•Acute lymphoblastic leukaemia (ALL)
•Chronic lymphoblastic leukaemia (CLL)
•Acute myeloid leukaemia (AML)
•Chronic myeloid leukaemia (CML)

By onset and progression

By cell type

ALL/CLLAML/CML

Proliferation of progenitor cells in the bone
marrow results in replacement of normal
haematopoeitic cells and bone marrow
failure.

Risk factors
•Acquired
-Cytotoxic chemotherapy
-Haematological e.g. myelodysplasia (AML)
•Inherited
-DNA repair defects, immune defects
-Other e.g. Down syndrome

Investigations in leukaemia
•History and examination
•Bloods
-FBC (anaemia, thrombocytopenia,
hyperleukocytosis, neutropenia)
-Smear (blasts, dysplastic neutrophils (2º AML))
-U&Es (hyperuricaemia)
-LDH
-Clotting screen
-LFTs, BUN/creatinine ratio
-Septic screen (if infection suspected)

•Imaging
-CXR, CT (pneumonia, mediastinal mass, lytic
bone lesions)
•BM biopsy
-Flow cytometry, cytogenetics and
immunohistochemistry
->30% blasts

Also known as ‘lymphocytic’.
Epidemiology
•Incidence = 1/50,000. Slight male predominance.
•Commonest type of childhood leukaemia (70%)
•Peak age 2-5 years, but later increase >50.

Pathophysiology
Formation of fusion genes  dysregulation of
proto-oncogene e.g. TEL-AML1 (25%).
85% are derived from B-cell precursors.

Findings specific for ALL
•Examination
-Lymphadenopathy
-Splenomegaly (10-20% presentation)
-CNS signs- more likely
•Bloods
-Anaemia- usually severe, signs present
-WBCs- variable, usually neutropenia
-Smear- smallish basophilic blasts, few
granules, hand-mirror cells
-Clotting- 10% ALL presents with DIC
•Imaging
-Mediastinal mass in some T cell ALL

Small basophilic
blasts with few
granules
Hand mirror
cells

Also known as ‘myelogenous’.
Epidemiology
•Incidence = 3.7/100,000. Slight male
predominance.
•Commonest type of adult leukaemia (90%)
•Can occur at any age but median is 70 years

Pathophysiology
Two classes of mutations may be required, similar
to ALL:

Findings specific for AML
•Examination
-Lymphadenopathy unusual
-Leukaemia cutis (10%), chloroma (rare)
•Bloods
-Anaemia- usually severe, signs present
-WBCs- variable, usually neutropenia
-Smear- Auer rods in large hypergranular
myeloblasts
-Hypokalaemia in monocytic leukaemia
-Clotting- DIC commoner in acute promyelocytic
leukaemia (M3)

Auer rods, oddly
shaped,
increased N:C

Treatment of acute leukaemia
Supportive:
Problem
Anaemia
Thrombocytopenia
DIC
Infection
Tumour lysis syndrome
CNS prophylaxis
Treatment
Packed RBCs
Platelets (if <10)
FFP, cyroprecipitate
Antibiotics, reverse
barrier nursing
Allopurinol/uricase
Intrathecal chemo e.g.
methotrexate, cytarabine

Definitive
Chemotherapy:
•Induction 4-6w
•Consolidation
•Maintenance (ALL only) 1-2y
-Longer in boys
Other
•Add in all-trans-retinoic-acid (ATRA) in PML
during induction
•Monoclonal Ab
•CNS radiotherapy
•BM transplantation

Prognosis of acute leukaemia
5 year survival rates
•ALL
-Children- 75%
-Adults- 40%
-Worse if <1 or >60, high WBC, >4w to
remission
•AML
-30-50%
-Better if BM Tx, children, worse if >60
Prognosis of acute leukaemia
•ALL
-Children- 75%
-Adults- 40%
-Worse if <1 or >60, high WBC, >4w to
remission
•AML
-30-50%
-Better if BM Tx, children, worse if >60

Risk factors
•Acquired
-Radiation (CML)
-Immunodeficiency e.g. HIV/AIDS, post-transplant
-Pesticides
•Inherited
-Family history (CLL)

98% develop from B cells.
Epidemiology
•Incidence = 4.2/100,000. Slight male
predominance.
•Most common form of leukaemia in the West
•Usually >55, median age 72, rare <40.

Pathophysiology
Largely unknown with no specific
genetic abnormalities.

Findings specific for CLL
Usually asymptomatic!
• Examination
-Lymphadenopathy/splenomegaly present in
late disease.
• Bloods
-WBCs- extremely high
-Smear- lymphocytosis with ‘smudge/basketball
cells’
• Other
-Richter’s syndrome
-Prolymphocytic transformation

Smudge cells-
destruction of
fragile
lymphocytes
during smear

Stepped-up production of granulocytes and their
precursors and failed apoptosis leads to insidious
progression towards a blast crisis.
Epidemiology
•Incidence= 0.6-2/100,000
•Can occur at any age but rare in children. Peak
incidence at 40-60
•Less common than AML, CLL

Pathophysiology
95% involve t(9;22)(q34;q11) translocation,
resulting in the Philadelphia chromosome. This
forms a fusion gene- BCR-ABL1 with constitutively
active tyrosine kinase activity.

Findings specific for CML
Usually asymptomatic!
•Examination
-Splenomegaly- may be only feature at latent
phase, massive later on
•Bloods
-Anaemia- mild, worsens with progression
-WBCs- extremely high
-Smear- leukocytosis with granulocyte left-shift

Leukocytosis,
increased
numbers of
banded
neutrophils

Treatment of chronic leukaemia
CLL
•Watchful waiting with regular monitoring
•Chemotherapy. Indications:
-Severe systemic symptoms
-Non-pred-responsive AI
anaemia/thrombocytopenia
-Progressive splenomegaly/lymphadenopathy
-Increased WBC/reduced ‘doubling time’
Treatment of chronic leukaemia

CML
•Imatinib
-Tyrosine kinase inhibitor, targets BCR-ABL1.
Greatly increases 5 year survival compared to
older drug therapies
-Initial treatment, continued indefinitely if optimal
response.

Other:
•Monoclonals
•Surgery
-Splenectomy for splenomegaly or
pancytopenia
•Radiotherapy
-Pallative for bulky LN or splenomegaly

Prognosis of chronic leukaemiaPrognosis of chronic leukaemia
•CLL
-Binet Staging
-Median approx. 10 years with terminal
progressive phase for 1-2 years
•CML
-Overall 5 year survival with imatinib now 89%
(or more?)
BM transplant is the only curative therapy

Acute Chronic
Lymphocytic Myelocytic Lymphocytic Myelocytic
Age Childhood Any Middle/Old Middle
Raised WBC
+/- +/- ++ ++
Anaemia
++ ++ +/- +
Thrombocytopenia
+ + +/- -
Lymphadenopathy
+ +/- + -
Splenomegaly
+ +/- + ++
Other CNS
involvement
Maintenance
required
Hand mirror
cells
Auer rods
APL
Leukaemia
cutis
Haemolytic
anaemia
Hypogammagl
obulinaemia
Smudge cells
Low ALP
Ph
chromosom
e targeted
by imatinib
Blast phase

 Non leukaemic malignancies
 Polycythaemia vera
 Essential thrombocythaemia
 Mastocytosis
 Form part of a spectrum with CML
 All are closely related to each other
 Associated with JAK2 mutations

 Clinical features
 Night sweats
 Hyperviscosity symptoms
 Pruritus after a hot bath
 Plethoric face
 Splenomegaly
 Haemorrhage
 Hypertension
 Gout

 Important lab features
 Increased Hb, HCT, Red cell mass
 Low serum EPO
 JAK2 mutation in 95%
 Treatment
 Venesection
 Cytotoxic myelosuppression
 Hydroxyurea
 Busulphan

What’s the difference between leukaemia and
lymphoma?

Hodgkin’s lymphoma
Originates from B cells in the germinal centres of
lymphoid tissue and is characterised by orderly
spread from one LN group to another.
Epidemiology
•Incidence = 2.2/100,000, 30% of all lymphoma
•Bimodal distribution with peaks at 15-30 and >50
years
•Slight male predominance

Risk factors
•Acquired
-HIV/AIDS- increases with CD4 count
-Previous non-Hodgkin’s lymphoma
-Autoimmune conditions
•Inherited
-Immune defects
-Family history of H/non-H lymphoma, CLL

Pathogenesis
Some proliferation of malignant Reed-Sternberg
cells (probably of B cell lineage) and abnormal
mononucleocytes.

Presentation
•Painless non-tender rubbery enlarged LN
-Cervical involvement in 60-70%, axillary in 10-
15%, inguinal in 6-12%
-May increase/decrease in size spontaneously
-May become ‘matted’ and non-mobile
-Contiguous progression to nearby groups
-Alcohol-induced pain
•Systemic symptoms
-Especially fever (30%), may be cyclic
-And severe pruritis (25%)
•Other
-Early satiety due to splenomegaly

Investigations
•FBC
-Exclude leukaemia, mononucleosis
•ESR/CRP
•LFTs
•U&Es
•CXR
-Lymphadenopathy, mediastinal expansion
•CT
-Thorax, abdomen for staging
•BM biopsy
•Other
-HIV, Monospot, LDH, thoracentesis, PET, LP,
MRI

•Lymph node USS and excision biopsy
Important to see the architecture of the LN!

Ann-Arbour staging
Automatic stage IV if extranodal involvement.
Systemic symptoms = B, extranodal = E, >10cm =
X, splenic involvement = S

Treatment
Supportive
•Fertility
•Cardiac function
•Respiratory function
•Tumour lysis syndrome
•Others, as indicated (see leukaemias slide)

Treatment
Definitive
•IA/IIA
-Radiotherapy alone- affected nodes and
prophylatically
-Chemo with radiotherapy of affected nodes
•IB/IIB/III/IV
-Chemo
•BM transplant
-If still progressive despite chemo or after
induction of remission after relapse

Non-Hodgkin’s lymphoma
A heterogeneous group of lymphoid tumours,
mostly of B cell origin. Characterised by irregular
pattern of spread and common extranodal disease,
they vary in their aggressiveness.
Epidemiology
•Incidence = 17/100,000
•Median age is >50
•Diffuse large B cell and follicular commonest

Risk factors
•Acquired
-Infection e.g. EBV (Burkitt’s, sinonasal), HTLV-1
(T cell), HCV, HHV8 (Kaposi’s), H. pylori (gastric
MALT)
-Previous chemotherapy/Hodgkin’s
-Autoimmune disorders e.g. Sjogren’s,
Hashimoto’s
-Immunodeficiency e.g. post-transplant, HIV/AIDS
•Inherited

Presentation
•Painless non-tender rubbery enlarged LN
-Non-contiguous progression
•Systemic symptoms
-Commoner in high-grade
•Rash
-Cutaneous involvement e.g. mycosis fungoides, anaplastic large-
cell etc.
•Abdominal pain, early satiety
-Splenomegaly but unusual as rarely massive
-Hepatomegaly
•Mass
-Testicular
-GI, symptoms of obstruction
•Shortness of breath, pleuritic chest pain, SVC syndrome
-Mediastinal mass in high grade
•Neurological
-Primary CNS lymphoma, commoner in immunosuppressed

Investigations
•FBC
-Anaemia, thrombocytopenia, neutropenia
-Thrombocytosis, lymphocytosis may occur
•ESR/CRP
•LFTs
•U&Es
-Obstructive nephropathy, hypercalcaemia
•Serology
-HIV, HTLV-1, HCV
•Imaging
-CXR-Intrathoracic lymphadenopathy, mediastinal expansion
-CT-Thorax, abdomen for staging
-Bone scan
-PET
-MRI- Brain, cord
-USS- Scrotum
•BM biopsy
-Should always be carried out

•Lymph node USS and excision biopsy

Treatment
•Low grade
-Localised (rare)- radiotherapy, surgery
-Disseminated- watch and wait or chemo when
symptomatic/organ dysfunction
-Gastric MALT- associated with H pylori,
antibiotic therapy curative in 90%
•High grade
-Aggressive chemo e.g. CHOP
-Maintenance not needed
-Allogenic stem cell transplantation
-CNS prophylaxis in very high grade e.g.
Burkitt’s

Prognosis of lymphoma
•Hodgkin’s- highly curable
-I/II- 90%
-IV- 65%
-Long-term sequelae of treatment
•Non-Hodgkin’s- vary widely (see IPI)
-Overall 63%
-Indolent follicular lymphoma I/II- 91% but may
not be curable
-DLBLC- curable with aggressive chemo

 Multiple Myeloma
 MGUS
 Waldenstrom’s macroglobulinaemia
 (Non-Hodgkin lymphoma)
 (CLL)

 Presdisposing factors
 Radiation
 Benzene
 Pesticides
 Epidemiology
 4 per 100,000 per year
 Median age 66 years
 Pathophysiology
 Post germinal centre B cell proliferation
 Monoclonal antibody

 Hypercalcaemia
 Renal impairment
 Anaemia
 Bone disease
 Hyperviscosity
 Amyloidosis (AL)
 Infection (recurrent)

 Amyloid L – Ig light chains
 paraproteinaemias
 Amyloid A – Protein A
 Chronic inflammation
 Amyloid TTR – Transthyretin
 Transthyretin abnormality
 Polyneuropathy,
 Restrictive cardiomyopathy
 Amyloid B2M – Beta 2 microglobulin
 Occurs in dialysis
 Carpal tunnel

 FBC and film
 ESR
 Urine dipstick
 24 hour urine collection
 U&Es
 Urate
 Albumin, calcium, phosphate, ALP
 Serum and urinary electrophoresis
 Serum Ig
 X-ray


1. Production of a single monoclonal antibody
(paraprotein)
 ‘M’ band in γglobulin region on serum/ urine
electrophoresis
2.Increased clonal plasma cells in the bone
marrow
 >20% monoclonal plasma cells on bone marrow
biopsy
3. Evidence of organ damage (‘CRAB HAI’)

 Prognosis
 MM remains an incurable disease
 Mean survival 3-4 yrs from diagnosis
 Treatment
 Specific
 Supportive

 Intensive or non intensive
 Intensive if <65
 Non intensive if >65
 Intensive
 4-6 cycles chemotherapy
 Cyclophosphamide, dexamethasone, thalidomide
 THEN autologous stem cell collection and transplant
 Non-intensive
 Chemo: Melphalan and cyclophosphamide

 Renal disease
 rehydration – 3L/day
 Bone disease
 Bisphosphonates
 Radiotherapy to bony lesions
 Corticosteroids
 Anaemia
 Transfusion/ EPO
 Hyperviscosity
 Plasmapheresis
 Infection

 Post germinal centre B cell proliferation
 Monoclonal antibody/ paraprotein production
 M Band
 BJP
 >20% monoclonal plasma cells in BM
 ‘CRAB HAI’
 Specific and supportive treatment
 Outcome still poor

 Often discovered incidentally in elderly
 Benign
 Characterised by:
 Low levels of paraprotein, normal levels of Ig
 <10% plasma cells in bone marrow
 Absence of lytic bone lesions
 Absent/minimal urinary BJP
 Absence of end organ damage associated with MM
 1% per year develop MM

 Lymphoplasmacytoid proliferation
 Similarities with CLL
 IgM paraprotein
 Plasma viscosity
 Organomegaly and lymphadenopathy more
common than in MM
 No end organ damage (cf MM)

A 66 year old man has a FBC done whilst being
tested for hypercholesterolaemia and was found
to have a WBC of 15.4x109
/L with the rest of the
count otherwise normal. The most likely
diagnosis is:
a)Infectious mononucleosis
b)CMV infection
c)ALL
d)Pertussis
e)Chronic lymphocytic leukaemia
e)

A 46 year old woman presents with weight loss and
abdominal enlargement. She has also noticed
she is sweating more than normal and her
temperature is 38C. She is found to have
hepatosplenomegaly (liver 2cm below RCM,
spleen 6cm below LCM). Lymph nodes are not
enlarged. FBC shows: WBC 98x109
/L, Hb 8.3g/L,
Plts 504x109
/L.
A blood smear was performed.

The blood smear shows increased numbers of
neutrophils, eosinophils and basophils. In
addition, there are increased numbers of
promyelocytes (but infrequent blast cells). What
is the optimum treatment for this patient?
a)Allogenic stem cell transplantation
b)Combination chemo
c)Imatinib
d)Blood transfusion to relieve symptoms
e)Rifampicin and isoniazid
c) (CML)

Which ONE of these is the most likely clinical
presentation of a child with acute lymphoblastic
leukaemia?
a) A 6 month history of fatigue and repeated upper
respiratory tract infection
b) Poor appetite and abdominal pain resulting from
swollen spleen
c) Swollen gums in the mouth
d) Recent history of bruising and tiredness
e) None- incidental finding
d) Anaemia and thrombocytopenia common

 A 67 year old lady is found to have an Hb of
18.9g/dL. Her erythropoeitin level is markedly
raised. Which of the following is the least likely
diagnosis?
 A) COPD
 B) Eisenmenger’s syndrome
 C) Polycythaemia vera
 D) Renal cell carcinoma
 E) Nepalese woman living at high altitude

Which ONE of these is NOT TRUE regarding the
Reed-Sternberg cell in Hodgkin’s lymphoma?
a) It is thought to be of B cell lineage‐
b) It is multinucleate
c) It represents the majority of cells in a lymph
node of Hodgkin's lymphoma
d) It usually expresses CD15 and CD30
e) Their absence has a high negative predictive
value
c) Near-pathogonomic but in the minority of cells

A 6 year old boy from Kenya develops swelling of
the jaw. The mass responds rapidly to
chemotherapy. What is the most likely diagnosis?
a) Burkitt's lymphoma
b) Follicular lymphoma
c) Mycosis fungoides
d) Lymphoblastic lymphoma
e) Enteropathy-associated T cell lymphoma
a) Burkitt’s lymphoma occurs in the context of
chronic malaria infection causing reduced immunity
to EBV. Also associated with AIDS.

 A 59 year old man receiving chemotherapy for
Non Hodgkin’s Lymphoma develops painful
haematuria. Which of the following is the most
likely cause of his symptoms?
 A) Rituximab
 B) Cyclophosphamide
 C) Adriamycin (doxorubicin/ hydroxydaunarubicin)
 D) Vincristine (oncovin)
 E) Prednisolone

Pulmonary fibrosis
 Busulfan
 Bleomycin
 Cardiotoxicity
 Adriamycin (doxorubicin)
 Haemorrhagic cystitis
 Cyclophosphamide
 Peripheral neuropathy
 Vincristine (oncovin)
 Vinblastine

 A 63 year old woman is about to commence
chemotherapy for treatment of MM. Which of
the following medications should she be
started on prior to chemotherapy?
 A) Colchicine
 B) Dexamethasone
 C) Diclofenac
 D) Allopurinol
 E) Hydroxychloroquine

 Malignant cells release intracellular contents
after the first dose of chemotherapy
 Hyperkalaemia
 Hyperuricaemia
 Renal failure
 Allopurinol inhibits xanthine oxidase and prevents
hyperuricaemia
 Large volumes of fluid should be given pre-chemo to
prevent renal failure

 Which one of the following is not consistent
with a diagnosis of MGUS?
 A) normal urinalysis
 B) normal renal function
 C) 20% plasma cells in bone marrow
 D) Normochromic, normocytic anaemia with
Rouleaux formations
 E) Absence of lytic bone lesions

 A patient has a sharp M band on serum
electrophoresis. Which of the following is least
consistent with this result?
 A) IgG MM
 B) Waldenstrom’ macroglobulinaemia
 C) AA amyloidosis
 D) MGUS
 E) CLL

 http://www.med-
ed.virginia.edu/courses/path/innes/wcd/lym
pleuk.cfm
 http://www.umm.edu/patiented/articles/ly
mphomas_non-hodgkins_000084.htm
 http://www.essentialhaematology6.com
 http://www.youtube.com/watch?
v=xWf8gvTF6hw&feature=related
 Watch from ~20 mins onwards

Haematological Malignancies

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Andere mochten auch

Andere mochten auch (20)

Ähnlich wie Haematological Malignancies

Ähnlich wie Haematological Malignancies (20)

Mehr von meducationdotnet

Mehr von meducationdotnet (20)

Haematological Malignancies

Hinweis der Redaktion