Malignant Haematology

MALIGNANT N.A.
OTHIENO-ABINYA,
HAEMATOLOGY FRCP
The haemato-/lymphoid cell
The malignant lymphocyte and
myeloid cell
The REAL/WHO Classification
LYMPHOID
Blood/circulation – leukaemia
( Acute and chronic)
Solid tissue – lymphoma
Bone marrow/bone - Myeloma
MYELOID
Blasts and promyelocytes – AML
Broad myeloid proliferation - CGL

Polycythaemia vera
Essential (primary) thrombocythaemia
Primary myelofibrosis
LYMPHOID MALIGNANCIES:
The three major classes:

-Malignant lymphomas
– HL
- NHL
-Plasma cell myeloma
-Lymphoid leukaemia
- ALL
- CLL/variants
Malignant Lymphomas
-4% of all malignant
disease
-Two broad categories:
HL (RS cell or
variants present
NHL (no RS cells or
variants)
HODGKIN’S LYMPHOMA:
Malignant lymphoma characterized by presence of
malignant Reed-Sternberg cells
-Less frequent than NHL

-At KNH about 40/year
-Highest incidence in non-Jewish population of Israel
(9.1/100, 000/year
-Lowest incidence in rural Poland (1./100, 000/year)
-M/F → 4/3:3/1 here
-Higher male preponderance seen in blacks all over
the world
Etiology & Risk Factors:
- Cause unknown
-?Immune depression
- Congenital
agammaglobulinemia
-Infectious etiology like ?EBV/other
virus.
-Single peak age of occurrence
at 17 years here
-Bimodal incidence with peak
age between 15-30 years and
50-70 years
-Japanese single peak at about
60 years
-Contiguous spread
-Involvement initially of a single
peripheral lymph node –
centripetal distribution
-Splenomegaly in 50% of
cases during the course of
the disease
-Constitutional systemic
symptoms in 30-40% of
cases at diagnosis, more
frequent in MC/LD
-Pel-Ebstein fever
-Other symptoms
Diagnosis and
Pathology
-History
-Physical examination
-Histology/IHC –
HRS –cells and
variants
HRS- like cells
Histological classification
-NLP - L & H (Popcorn) variants of HRS
cells
- CD20, CD45, EMA (+)
-Classical HL - HRS cells/variants
- CD15, CD25, CD30, EBV
(+)
Subtypes:
- NS (Lacunar cells)
- LRC (popcorn cells)
- MC
- LD
STAGING
-Costwalds/Ann Arbor Staging.
Costwalds:
I – single LN region/lymphoid structure
II - 2 LN regions on same side of diaphragm
III – LN regions  lymphoid structure on both sides
of diaphragm
IV – Extranodal sites beyond E
- X – Bulky disease
- E – Single extralymphatic site systemic
- A – No systemic symptoms
- B – Systemic symptoms present
TREATMENT
Early Stage (I/IIA) Late Stage III /IV
Good Poor prognosis
prognosis
ABVD X 2  ABVD X 4  ABVD X 6 – 8
IFRT (20-25 IFRT (20-25 Gy) BEACOPPDE 
Gy) Consolidating RT to
areas of bulky disease
NON-HODGKIN’S
LYMPHOMAS
-All are lymphocytic
Epidemiology:
-Annual incidence of 4-6/100, 000 population/year.
-NHL/HD in Kenya – 3/1
- BL influence
- BL epidemiology
-HIV infection
-HIV/NHL rates declining since advent of HAART
Etiology and pathogenesis:
- Multifactorial
Evolution of Disease:
-Multicentric
-Haematogenous/
lymphatic spread
-75% to 80% B-cell line
-20 to 25% T-cell line
Clinical Features:
-Painless swelling of
lymph
-Swelling of other organs
-Compression of vital
structures
-Features of bone marrow
failure
Diagnosis:
-History
-Physical examination
-Biopsy – histology/IHC,
molecular
 chromosomal
translocation
 DNA profiling
-Staging procedures:
History, Examination,
imaging, labs.
-Staging classification –
Ann Arbor
TREATMENT
INDOLENT PHENOTYPE:
Early (St I & II) Late (Stage III &

IV
Asymptomatic Symptomatic
IFRT Watchful Chl-OP/CVP/R-X
TNI Waiting CP + IFRT/EFRT
STNI CHOP ± R
HDT + SCT
R-Bend,
R-bort/Len
Aggressive and highly
Aggressive:
-St.IA – CCT X3 → EFRT
-Others – CHOP,
CHOEP, R-CHOP
-R-others
MULTIPLE MYELOMA
-Neoplastic proliferation of
plasma cells
-Defective synthesis and
secretion of single clone of
immunoglobulins
(paraproteins), or one of its
constituent polypeptide chains
(heavy or light)
-Paraprotein levels in
serum and/or urine –
usually but does not
always correlate with
myeloma cell load.
-MGUS- now considered
precursor of MM.
- Serum
immunoelectrophoresis
- 60%IgG
- 20 – 25% IgA
- 1% IgD
- 1gE – very rare
-BJP phenomenon
Clinical manifestations –
dependent on:
- Insidious onset
- Bone pains, aches, #s
- Renal failure
- Infections
PHYSICAL EXAMINATION
-Middle aged to elderly
-Pallor
-Dehydration
-Bone tenderness/#s
Diagnosis –
- Paraproteins in serum and/or urine
- x-ray changes
- Bone marrow plasmacytosis > 10%
Others:
- Calcium
-Cryoglobulinemia
- Rouleaux formation of rbcs
-ESR
-Renal failure
-Anaemia
Diagnostic examination:
-Skeletal survey/MRI scans
-Serum + urine
electrophoresis
-Biopsy of plasmacytoma
-Bone marrow
biopsy/aspirate
-Peripheral blood
examination
INTERNATIONAL STAGING SYSTEM
(ISS) FOR MULTIPLE MYELOMA
Group I - combination of β2M <35 g/litre and serum

albumin > 35 g/litre.
Group II - β2M <35g/litre and serum albumin

<35g/litre,or β-2-M between 35-55g/litre irrespective
of serum albumin.
Group III - β2M >55g/litre.
Natural history: - Control for 2 – 3 years
then refractory
Management:
Support –
- Hydration
- Hypercalcemia – bisphosphanates
- Ambulation/Analgesia
- Fixing of #s/RT
- Anaemia
- Infections
- Renal failure
Management of hypeviscosity
Specific: Transplant
Candidates:
- Len/Dex +/- bortezomib
- VAD 1/VAD2
Non transplant candidates
- MPT
- VMCP, etc.
- CP
Stem cell transplant - Autologous
- Allogeneic
Relapse/Resistant – Bortezomib,
carfilzomib,lenalidomide, pomalidomide, etc.
LYMPHOID LEUKAEMIAS
Leukaemia –
Blood cancer - Acute and
chronic
Acute Lymphoblastic Leukaemia
-Uncontrolled monoclonal
proliferation of lymphoblasts in
bone marrow  replacement of
normal components of bone
marrow.
-Diminishing production of normal
blood cells
 Anaemia
 Infection
 Haemorrhage
Epidemiology:
-Incidence in Kenya/Developing
countries not known
-Data from US/Europe
-85% of childhood acute
leukaemia
-Rare between 40-70 years
then
small peak
Symptoms and Findings:
Mainly due to bone marrow failure
-Anaemia
-Haemorrhage
-Infections
Infiltrations:
-Glandular swellings
-Splenohepatomegaly
-Other organ malfunction – CNS
manifestations
Diagnostic Examination:
-PB blasts – almost always – 60-
90%
-Thrombocytopenia – almost
invariable
-Bone marrow mandatory
-C x R – mediastinal widening in
10-20% of cases typical of T-cell
variant
Treatment:
Preparation – Infection, anaemia,
etc.
Induction: VCR/PRD/DOXO OR DNR
-vincristine 1.4 mg/m2 I.V. days 1, 8,
15,
-Prednisone 60mg/m2 PO days 1-30
then taper gradually
-Doxorubicin 50mg/m2 I.V. days 1
Repeat at 21 days intervals
Usually it takes two cycles to CR
CONSOLIDATION?
-HDMTX, HIDAC, CTX
-6MP/Idarubicin,
Etoposide
-Teniposide,
mitoxantrone,
Amsacrine
CNS PROPHYGLAXIS:
-MTX it
-Craniospinal irradiation
Maintenance:
-MTX + 6MP oral
-Re-inductions at 3 monthly
intervals
Relapse:
-Re-induce then HDT + SC
Transplant
CHRONIC LYMPHOCYTIC
LEUKAEMIA (CLL)
-Monoclonal neoplasm in
which the malignant cell is
small, mature
(morphologically) B-cell
(usually).
-Slow proliferation, long
living
Epidemiology:
-Middle aged to elderly
-Should not be diagnosed
below 30 years
-More common in caucasians
than oriental populations
-25% of all leukaemias
-3/100,000 population in US
-M/F = 5/2 at KNH
SYMPTOMS AND FINDINGS:
-Onset usually insidious
-Progressive nodal enlargement
-Asthenia, malaise, repeated infections,
anorexia, weight loss night sweats, easy
fatiguability
Examination:
-Generalised lymphodenopathy
-Splenomegaly in just over 50%
-Anaemia
-Haemorrhagic manifestations
Pathology and Diagnosis:
-Peripheral blood lymphocytosis
wbc usually > 15 x 109/litre
with absolute lymphocytes > 5
x 109/litre
Needed at least 4 x 109/litre
-Smudge cells
-90% of PBWBC usually
lymphocytes
Flow cytometry:
-s1gM weekly +ve
-CD5 +, CD10-, CD19+,
CD20+, CD79a+, CD22,
CD23+
Marrow:
- Lymphocytosis of at
least 40% of nucleated
STAGING AND
PROGNOSTICATION:
Binet:
A – < 3 sites of organ enlargement,
Hb ≥ 10g.dl, platelets > 100 x
109/litre
B -  3 sites of organ enlargement,
Hb > 10g/dl, platelets > 100 x
109/litre
C – Number of sites disregarded
Hb < 10g/dl, platelets < 100 x109
/litre
Treatment:
-Watchful waiting
-Steroids
-Alkylators
-Alkylator/purine analog
combinations
-Anti CD 20 Mab
(Rituximab).
BCR-ABL NEGATIVE
MYELOPROLIFERATIVE
NEOPLASMS
WHO 2008- 5 categories of myeloid malignancies including:
AML
MDS
MPN
MDS/MPN Overlap syndromes
PDGFR/FGFR1- rearranged myeloid/lymphoid neoplasms with
eosinophilia.
ACUTE MYELOID
LEUKAEMA
Heterogeneous group of neoplastic diseases

- Monoclonal.
- If not well treated - uniformly fatal within
months.
Epidemiology
- Disease of adults
- Racial differences
- Slight male preponderance
Aetiology and
Pathogenesis:
-Ionizing radiation
-Chemical substances -
benzene,
- Anticancer drugs
- ?Viruses
Familial - Concordance of
20% amongst identical twins
Other congenital conditions:
- Down’s syndrome
-Bloom’s syndrome
-Ataxia-telangiectasia.
Clinical
features:
- Anaemia
- Infections
- Bleeding
- Infiltrations
SEPSIS
SUBCONJUNCTIVAL
HAEMORRHAGE
Diagnostic Examination:
PBF
- Up to 30% AML cases have
normal PB leukocyte counts
- Most AML oligoblastic i.e.
myeloblasts seen in PBF in only 25-
40% of cases.
- Oligoblastic, oligocytic in small %
BM aspirate/biopsy
CYTOCHEMISTRY
Cytochemistry :
Myeloperoxidase,
Sudan black
Combined esterase
IMMUNOPHENOTYPING
Cytochemistry can be omitted
and instead 4 colour flow
cytometry be performed.
Immunophenotyping:
CD3, CD7, CD13, CD14, CD33,
CD34, CD64, CD117
CYTOGENETICS
CYTOGENETICS
(with RT-PCR for AML1-ETO and CBF-MYH11
in non-APL, and PML-RARA in suspected APL
FISH in selected cases.
CISH
SISH
TREATMENT STRATEGIES:
- Vital support
Nutrition
Hydration
Blood transfusion
HYGIENE /DISCIPLINE
ANTIBIOTICS/Antimicrobials
PLATELETS/Blood
Allopurinol
SPECIFIC TREATMENT -
Induction - Anthracycline/ARA-C
- Mitoxantrone/Ara-c
Etoposide
Methyl-GAG
- Doxorubicin/Ara-c
APL : ATRA+ Chemo/AS2 O3
Post remission- Consolidation,
maintenance
INDUCTION
INTENSIFICATION THERAPY IN
REMISSION
Allogeneic haematopoietic stem cell

transplantation
?Role of autologous transplants in

relapse
CHRONIC MYELOID LEUKAEMIA
- Neoplastic proliferation of
haematopoietic stem cell
- MPN
Ph+ in >90% of cases
BCR-ABL +ve in 100%
Aetiology:
- Not known for most individuals.
- Ionizing radiation.
-Exposure to petrochemicals
Incidence and
Prevalence:
- 1.5/100 000
population/year
- All age groups affected,
peak between 20-60 years
- <2 years, Ph-ve
- MF = 3/2
Pathogenesis and
Mechanisms:
- >90% Ph+ve
- t (9;22) (q34;q11) 
BCR/ABL protein (210kd),
not 145 kd ABL protein TK
activity.
Clinical presentation:
- Left hypochondriac swelling and

pain
- others
- Examination - Splenomegaly
- Others
Peripheral blood examination
Bone marrow examination
- Philadelphia
chromosome/BCR-ABL fusion
MASSIVE SPLEEN IN
CML
Treatment of CPCGL:
-Imatinib
-Dasatinib
-Nilotinib
- HC>IFN/Ara-c
-??Busulphan
Transplant
ACCELERATED AND BP:
Imatinib bosutinib,
- Dasatinib ponatinib
- Nilotinib omacetaxine
- CCT
- ?Decitabine
- ?Azacytidine
- Allo transplant

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MALIGNANT N.A.

Broad myeloid proliferation - CGL

The three major classes:

-Less frequent than NHL

Early (St I & II) Late (Stage III &

Group I - combination of β2M <35 g/litre and serum

Group II - β2M <35g/litre and serum albumin

Heterogeneous group of neoplastic diseases

Allogeneic haematopoietic stem cell

?Role of autologous transplants in

- Left hypochondriac swelling and

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