Mary Frances McMullin

m.mcmullin@qub.ac.uk
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Conflict of interest
Speakers fees: Novartis and Bristol-
Myers Squibb
Advisory boards : Novartis, Bristol-
Myers Squibb and Takeda
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Definition: Blood Dyscrasia
A pathological condition in which any of
the constituents of the blood are
abnormal in structure, function or quality
as in leukaemia or haemophilia
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Outline
Myelodysplastic syndromes

Autoimmune Haemolytic anaemia

Multiple myeloma
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Cytopenia (s)
Dysplasia of one or more major myeloid
cell lines
Ineffective haematopoiesis
Increased risk of development of acute
myeloid leukaemia
Enhanced degree of apoptosis
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MDS: Typically a disease of the
elderly
80% of patients
diagnosed with
MDS are over
60 years

Elderly patients
are not usually
eligible for
bone marrow
transplantation
1
Adapted from Williamson PJ, et
al.
2

MDS
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4
9
16
26
52
59
61
89
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10
20
30
40
50
60
70
80
90
30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 80+
Age-specific incidence rates
(per 100,000)
Less than 50: 0.5
5059: 5.3
6069: 15
7079: 49
80 and over: 89
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Clinical features
Anaemia often macrocytic
Bleeding and bruising
Infections

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HB < 100g/L
Absolute neutrophil count < 1.8 x 10
9
/L
Platelets< 100 x 10
9
/L

Values above threshold do not exclude a
diagnosis of MDS
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Subtype Blood Bone marrow
Refractory anaemia (RA)
Refractory neutropenia (RN)
Refractory thrombocytopenia (RT)
Anaemia; no or rare blasts
Neutropenia
Thrombocytopenia
Erythroid dysplasia only; <5% blasts; <
15% ringed sideroblasts
Refractory cytopenia with multilineage
dysplasia (RCMD)
Cytopenias (bicytopenia or
pancytopenia): no or rare blasts;
no Auer rods; <1x10
9
/L
monocytes
Dysplasia in 10% of cells; in 2 myeloid
cell lines; <5% blasts; no Auer rods;
<15% ringed sideroblasts
Refractory anaemia with ringed
sideroblasts (RARS)
Anaemia; no blasts Erythroid dysplasia only; <5% blasts;
15% ringed sideroblasts
Refractory anaemia with excess
blasts-1 (RAEB-1)
Cytopenias; <5% blasts; no Auer
rods; <1x10
9
/L monocytes
Unilineage or multilineage dysplasia; 5%
to 9% blasts; no Auer rods.
Refractory anaemia with excess
blasts-2 (RAEB-2)
Cytopenias; 5% to 19% blasts;
Auer rods +/-; <1x10
9
/L
monocytes
Unilineage or multilineage dysplasia;
10% to 19% blasts; Auer rods +/-
Myelodysplastic syndrome,
unclassified (MDS-U)
Cytopenias; no or rare blasts; no
Auer rods
Unilineage dysplasia in granulocytes or
megakaryocytes; >5% blasts; no Auer
rods
MDS associated with isolated del 5q Anaemia; >5% blasts; platelets
normal or increased
Normal to increased megakaryocytes
with hypolobulated nuclei; >5% blasts; no
Auer rods; isolated del 5q
WHO classification of Myelodysplastic syndromes
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Survival by WHO classification

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Diagnosis
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Laboratory Features
Pancytopenia
Anaemia: macrocytic or diamorphic
Neutropenia
Thrombocytopenia
Blasts in peripheral blood
Trilineage dysplasia in bone marrow
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Diamorphic red cells
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Treatment options for MDS

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Clinical vignette (1)
Female: DOB 2/11/1924
2011: referred with anaemia and easy
bruising
Previous aortic and mitral valve
replacement on warfarin
Hb 97g/L, WCC 3.7 x 10
9
/L, neuts 1.9 x
10
9
/L and platelets 36 x 10
9
/L
Bone marrow: hypercellular with trilineage
dysplasia
Myelodysplasia: WHO refractory cytopenia
with multilineage dysplasia
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Treatment
Darbopoeitin 100ug SC once every 2
weeks
4 weeks later Hb 113g/L
Over next 2 years Hb maintained
between 105 and 120g/L on
darbopoietin
Died March 2013 following a fall and
fractured femur
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Autoimmune haemolytic anaemia
Antibody production by the body against
its own red cells
warm antibodies reacting at 37
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C
or cold antibodies reacting at 4
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Clinical features
Symptoms and signs of anaemia
Jaundice
Splenomegaly
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Laboratory Features
Anaemia
Increased reticulocytes
Spherocytes on blood film
Increased bilirubin
Increased LDH
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Treatment
Corticosteroids
Splenectomy
Immunosuppression
Folic acid
Blood transfusion
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Clinical vignette (2)
Female DOB: 13/8/1928
2009: Admitted on medical take with
anaemia
Hb76g/L, MCV 100fl, 42.3 pg (27-32),
MCHC 412g/L (320-360), WCC 4.5 x
10
9
/L, platelets 194 x 10
9
/L, retics 3.5%.
Total bilirubin 59umol/L, LDH 694U/L
Direct Coombs test positive
Antibody screen: Non Specific Cold
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Follow up
No underlying cause identified
Prednisolone: minor transient response
Transfused
Refused further immune suppression
Transfusion: 2 units every 2-3 months
Continuing fully functioning with
infrequent transfusions to maintain her
Hb >100g/L
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Multiple Myeloma
Neoplastic clonal plasma cell
accumulation in the bone marrow
98% of cases over 40 years with peak
incidence in 7
th
decade
Develops from a monoclonal
gammopathy of undetermined
significance
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Symptomatic myeloma
Monoclonal protein in serum and/or
urine
Increased clonal plasma cells in bone
marrow
Related organ or tissue impairment
Tissue damage:
CRAB ( hypercalcaemia, renal
impairment, anaemia, bone disease).
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Clinical features
Bone pain, vertebral collapse,
pathological fractures
Features of anaemia
Recurrent infections
Renal failure and/or hypercalcaemia
Bleeding and bruising
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Laboratory features
Paraprotein
Elevated serum free light chains
Immune paresis: reduced normal serum
immunoglobin levels
Normochromic normocytic or macrocytic
anaemia
High ESR

Raised serum calcium
Raised serum creatinine
Low serum albumin
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Plasma protein electrophoresis showing monoclonal IgG kappa band
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Treatment options
Suitable for intensive
chemotherapy
Courses of
chemotherapy (CDT)
followed by ASCT
Plateau
Relapse
Bortezomib
Lenalidomide, etc
Not suitable for
intensive therapy
Melphalan, prednisolone
and thalidomide
Plateau
Relapse
Bortezomib
Lenalidomide etc
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Supportive/emergency care
Renal failure: rehydrate and dialysis
Hypercalcaemia: rehydration and
corticosteroids and bisphosphonates
Compression paraplegia:
decompression or irradiation
Anaemia: transfusion or erythropoietin
Infections: rapid antibiotics
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Clinical vignette (3)
Female: DOB 21.11.1937
In 2005 referred with IgA kappa
paraprotein 3g/L
SOB with respiratory disease (smoker)
Hb 110g/L, with normal WCC and pts
Normal biochemistry and no immune
paresis
Normal skelatal survey and normal bone
marrow aspirate
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Follow-up
Seen every 6mths with stable
paraprotein
2013:IgA kappa paraprotein 5g/L
Swelling over right scapula
Lytic lesion and skeletal survey small
number of further lytic lesions
Bone marrow 10% plasma cells
Due to start on MPT
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Survival in myeloma
Non-intensive 3-4 years
Autologous transplant increases by
1- 2 years
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Monoclonal gammopathy of
undetermined significance
1% of population over 50years
3% of those over 70 years
Rate of development of myeloma 1%
per year
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