Upload
anthony-hartono
View
225
Download
0
Embed Size (px)
Citation preview
8/12/2019 McMullin Blood Dyscrasias
1/47
Mary Frances McMullin
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
2/47
M
Conflict of interest
Speakers fees: Novartis and Bristol-
Myers Squibb
Advisory boards : Novartis, Bristol-
Myers Squibb and Takeda
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
3/47
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
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
4/47
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
5/47
Outline
Myelodysplastic syndromes
Autoimmune Haemolytic anaemia
Multiple myeloma
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
6/47
8/12/2019 McMullin Blood Dyscrasias
7/47
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
transplantation1
Adapted from Williamson PJ, et
al.2
MDS
2 1 2 2 4
9
16
26
52
59 61
89
0
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: 5.36069: 15
7079: 49
80 and over: 89
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
8/47
Clinical features
Anaemia often macrocytic
Bleeding and bruising
Infections
M
FMcMu
llin-BGS
Spring2
013
8/12/2019 McMullin Blood Dyscrasias
9/47
Threshold for cytopenia HB < 100g/L
Absolute neutrophil count < 1.8 x 109/L
Platelets< 100 x 109/L
Values above threshold do not exclude a
diagnosis of MDS
M
FMcMu
llin-BGS
Spring
2013
8/12/2019 McMullin Blood Dyscrasias
10/47
Subtype Blood Bone marrow
Refractory anaemia (RA)
Refractory neutropenia (RN)Refractory thrombocytopenia (RT)
Anaemia; no or rare blasts
NeutropeniaThrombocytopenia
Erythroid dysplasia only;
8/12/2019 McMullin Blood Dyscrasias
11/47
Survival by WHO classification
3
Diagnosis
M
FMcMu
llin-BGS
Spring
2013
8/12/2019 McMullin Blood Dyscrasias
12/47
Laboratory Features
Pancytopenia
Anaemia: macrocytic or diamorphic
Neutropenia
Thrombocytopenia
Blasts in peripheral blood
Trilineage dysplasia in bone marrow
M
FMcMu
llin-BGS
Spring
2013
8/12/2019 McMullin Blood Dyscrasias
13/47
Diamorphic red cells
M
FMcMu
llin-BGS
Spring
2013
8/12/2019 McMullin Blood Dyscrasias
14/47M
FMcMu
llin-BG
SSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
15/47M
FMcMu
llin-BG
SSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
16/47M
FMcMu
llin-BG
SSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=7qwQFKCTwXaeXM&tbnid=Wg7kuyvkWNrMiM:&ved=0CAUQjRw&url=http://www.pathologyoutlines.com/topic/myeloproliferativeRCMD.html&ei=1QRvUb3aIoPP0QXW9IDQDQ&bvm=bv.45368065,d.d2k&psig=AFQjCNGRmBnK2iRSoVcCV6vhBcYDz2baDA&ust=13663165335254968/12/2019 McMullin Blood Dyscrasias
17/47
Treatment options for MDS
.
M
FMcMu
llin-BG
SSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
18/47
Clinical vignette (1)
Female: DOB 2/11/1924
2011: referred with anaemia and easybruising
Previous aortic and mitral valvereplacement on warfarin
Hb 97g/L, WCC 3.7 x 109/L, neuts 1.9 x109/L and platelets 36 x 109/L
Bone marrow: hypercellular with trilineage
dysplasia Myelodysplasia: WHO refractory cytopenia
with multilineage dysplasia
M
FMcMu
llin-BG
SSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
19/47M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
20/47
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 andfractured femur
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
21/47
Autoimmune haemolytic anaemia
Antibody production by the body against
its own red cells
warm antibodies reacting at 370C
or cold antibodies reacting at 40C
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
22/47
Clinical features
Symptoms and signs of anaemia
Jaundice
Splenomegaly
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
23/47
Laboratory Features
Anaemia
Increased reticulocytes
Spherocytes on blood film
Increased bilirubin
Increased LDH
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
24/47M
FMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=OIry2chUZhZlEM&tbnid=ZwIoBRa1XQYFtM:&ved=0CAUQjRw&url=http://studydroid.com/index.php?page=viewPack&packId=205124&ei=ksFtUfLnIu-k0AXos4AY&bvm=bv.45218183,d.d2k&psig=AFQjCNE3h4PraCWQyyxhgRmgMKkVCV838A&ust=13662338160362498/12/2019 McMullin Blood Dyscrasias
25/47M
FMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=YcTb1I3IadpfAM&tbnid=3G1-eFrqUT2owM:&ved=0CAUQjRw&url=http://www.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2020/2020%20Exam%20Reviews/Exam%201/CH17%20Hematopoiesis.htm&ei=G8JtUZbNGOSU0AXJqYDYCQ&bvm=bv.45218183,d.d2k&psig=AFQjCNF0InS1yuY8DP8DPoAKWGjyCf4AZQ&ust=13662339488988728/12/2019 McMullin Blood Dyscrasias
26/47M
FMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=FrxjpwHKxmeztM&tbnid=FL0cAwG1TdlF0M:&ved=0CAUQjRw&url=http://www.merckmanuals.com/professional/hematology_and_oncology/anemias_caused_by_hemolysis/autoimmune_hemolytic_anemia.html&ei=5r9tUevCIIbC0QWZ2IG4Dg&bvm=bv.45218183,d.d2k&psig=AFQjCNEHvRmpaxrdWit9Tvsgh2WD0P-XyQ&ust=13662333425098038/12/2019 McMullin Blood Dyscrasias
27/47
Treatment
Corticosteroids
Splenectomy
Immunosuppression
Folic acid
Blood transfusion
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
28/47
Clinical vignette (2)
Female DOB: 13/8/1928
2009: Admitted on medical take withanaemia
Hb76g/L, MCV 100fl, 42.3 pg (27-32),MCHC 412g/L (320-360), WCC 4.5 x109/L, platelets 194 x 109/L, retics 3.5%.
Total bilirubin 59umol/L, LDH 694U/L
Direct Coombs test positive
Antibody screen: Non Specific Cold
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
29/47M
FMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=aBaPmqGWFxhQAM&tbnid=_qbspFqE3GKV5M:&ved=0CAUQjRw&url=http://www.pathologystudent.com/?p=1045&ei=mr9tUb3DG-fL0AXZw4CgCQ&bvm=bv.45218183,d.d2k&psig=AFQjCNEHvRmpaxrdWit9Tvsgh2WD0P-XyQ&ust=13662333425098038/12/2019 McMullin Blood Dyscrasias
30/47
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
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
31/47
Multiple Myeloma
Neoplastic clonal plasma cell
accumulation in the bone marrow
98% of cases over 40 years with peak
incidence in 7thdecade
Develops from a monoclonal
gammopathy of undetermined
significance
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
32/47
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, renalimpairment, anaemia, bone disease).
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
33/47
Clinical features
Bone pain, vertebral collapse,
pathological fractures
Features of anaemia
Recurrent infections
Renal failure and/or hypercalcaemia
Bleeding and bruising
M
FMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
34/47
MFMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=C_XgK1uocbbAwM&tbnid=LHF6jYB0xoMRCM:&ved=0CAUQjRw&url=http://www.wheelessonline.com/ortho/multiple_myeloma&ei=2MNtUc_ZGqTC0QWHjYGoAg&bvm=bv.45218183,d.d2k&psig=AFQjCNGw0410_s8UNlnq8zmI4x7mr58mMg&ust=13662340882637028/12/2019 McMullin Blood Dyscrasias
35/47
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
36/47
Laboratory features
Paraprotein Elevated serum free light chains
Immune paresis: reduced normal serumimmunoglobin levels
Normochromic normocytic or macrocyticanaemia
High ESR
Raised serum calcium Raised serum creatinine
Low serum albumin
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
37/47
Plasma protein electrophoresis showing monoclonal IgG kappa bandMFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
38/47
MFMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=PpXVJf7VH6QLwM&tbnid=n-34pM-5DPWlBM:&ved=0CAUQjRw&url=http://www.bindingsite.be/intactimmunoglobulinmultiplemyeloma&ei=CcZtUYvMCubI0QWUtoCACg&psig=AFQjCNEFwhYjVhZRgwSkfshyGhPZBy2rAg&ust=13662349697153028/12/2019 McMullin Blood Dyscrasias
39/47
MFMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=7_hgpp5CtU-lUM&tbnid=qCmFJ8U0SRigIM:&ved=0CAUQjRw&url=http://www.personal.psu.edu/afr3/blogs/SIOW/2011/11/multiple-myeloma.html&ei=-sJtUfzOJoax0AW7j4CgCQ&bvm=bv.45218183,d.d2k&psig=AFQjCNGw0410_s8UNlnq8zmI4x7mr58mMg&ust=13662340882637028/12/2019 McMullin Blood Dyscrasias
40/47
Treatment options
Suitable for intensivechemotherapy
Courses of
chemotherapy (CDT)
followed by ASCT Plateau
Relapse
Bortezomib
Lenalidomide, etc
Not suitable forintensive therapy
Melphalan, prednisolone
and thalidomide
Plateau
Relapse
Bortezomib
Lenalidomide etc
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
41/47
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
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
42/47
Clinical vignette (3)
Female: DOB 21.11.1937
In 2005 referred with IgA kappaparaprotein 3g/L
SOB with respiratory disease (smoker) Hb 110g/L, with normal WCC and pts
Normal biochemistry and no immuneparesis
Normal skelatal survey and normal bonemarrow aspirate
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
43/47
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
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
44/47
Survival in myeloma
Non-intensive 3-4 years
Autologous transplant increases by
1- 2 years
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
45/47
Monoclonal gammopathy of
undetermined significance
1% of population over 50years
3% of those over 70 years
Rate of development of myeloma 1%
per year
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
46/47
MFMcM
ullin
-BGSSp
ring20
13
8/12/2019 McMullin Blood Dyscrasias
47/47
MFMcM
ullin
-BGSSp
ring20
13
http://www.google.co.uk/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=d37qBd7a4NuieM&tbnid=jrkjPVxvaHuYkM:&ved=0CAUQjRw&url=http://www.okmgma.com/contactus.cfm&ei=Gb9tUezgO-jK0QWZ-4GYCw&bvm=bv.45218183,d.d2k&psig=AFQjCNHw9RGQgtlQGQPF-0TOK9hc184o-w&ust=1366233145609056