1. ITP in the adult
Blood.2011;117(16):4190-4207
Presentor: 周益聖
I nstructor: 蕭樑材
2. Grade system of recommendation
IWG definition
Diagnosis
Course
Bleeding risk
Treatment of fresh case
IVIG vs High dose MTP + prednisolone vs placebo
HD dexamethasone
Treatment of refractory/relapase cases after initial steroid
Splenectomy
TPO agonists
Rituximab
Take home massage
3. 1A, 1B, 1C, 2A, 2B, 2C
Number: strength of recommendation
1-we recommend..
2- we suggest..
Alphabetical: quality of evidence
A- RCTs or exceptionally strong observation studies
B- RCTs with limitation or strong observation
studies
C-RCTs with serious flaws , weaker observations or
indirect evidence
Blood.2011;117(16):4190-4207
4. Newly diagnosed: diagnosis to 3 months
Persistent: 3 to 12 months from diagnosis
Chronic: more than 12 months
Newly 12
Diagnosis diagnosed 3 months Persistent Chronic
months
Blood. 2009;113(11):2386-2393.
5. Recommend
Check HCV and HIV (1B)
Suggest
Further investigation if abnormalities other
than thrombocytopenia (including IDA) in the
blood count or smear (2C)
Bone marrow examination not necessary
irrespective of age with typical ITP(2C)
Insufficient evidence to recommend routine
check anti-platelet Ab , APA, ANA, TPO levels
Blood.2011;117(16):4190-4207
6. Antiphospholipid syndrome
Autoimmune thrombocytopenia(eg Evans
syndrome)
Common variable immune deficiency
Drug administration side effect
Infection with CMV, Helicobacter pylori, HCV,
HIV, varicella zoster
Lymphoproliferative disorder
Vaccination side effect
SLE
Blood.2011;117(16):4190-4207
7. Flow Cytometry using donor platelets as
SPRCA ( Solid phase red cell adherence
target cells detects detects autoAb in
assay)for plasma anti-platelet Ab
70 %(31/44) in ITP
Sensitivity: 50% (22/44),
J Chin Med Assoc 2006;69(12):569-574.
Specificty:100%
8. Suggest
Treat newly diagnosed patients with platelet count
<30x10^9/L(2C)
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
(2B)
IVIG combined with steroid if more rapid increase
in platelet count desired(2B)
IVIG or anti-D as first line if steroid
contraindicated(2C)
IVIG dose : 1g/Kg as one-time dose, repeated higher
doses if necessary (2B)
Br J Haematol 1999;107(4):716-719.
9. Suggest
Treat newly diagnosed patients with platelet
count <30x10^9/L(2C)
Longer courses of steroid are preferred than
short courses of steroid or IVIG as first-line
treatment (2B)
IVIG combined with steroid if more rapid
increase in platelet count desired(2B)
IVIG or anti-D as first line if steroid
contraindicated(2C)
IVIG dose : 1g/Kg as one-time dose, repeated if
necessary (2B) Blood.2011;117(16):4190-4207
10. 72 pts : steroid only ( 1mg/ kg/ day)
9 pts: high dose IVIG (0.5-2g/kg)
28pts: combined both
5 pts: conservative
CR:>100X10^9/L
PR: 30X10^9/L ~ 100X10^9/L
Haematologica 2006;91(8):1041-1045.
12. 47.8% in aged
Plt<30x10^9/L
>60 yrs @ 5 yrs
Fatal
bleeding
2.2% in aged <40
yrs @ 5 yrs
76% in aged >60
years at 2 years
Non-fatal
bleeding
Arch Intern Med 2000;160(11):1630-1638.
13. Suggest
Treat newly diagnosed patients with platelet
count <30x10^9/L(2C)
Longer courses of steroid are preferred than
short courses of steroid or IVIG as first-line
treatment (2B)
IVIG combined with steroid if more rapid
increase in platelet count desired(2B)
IVIG or anti-D as first line if steroid
contraindicated(2C)
IVIG dose : 1g/Kg as one-time dose, repeated if
necessary (2B) Blood.2011;117(16):4190-4207
17. Dex
40mg/day
D1-4
-Dex
40mg/day
D1-4
-Pred 15mg
maintian
N Engl J Med
2003;349(9):831-836.
18. -Plt at D10<90X10^9/L->70% relapse
-36% required additional treatment
-42% had plt >50X10^9/L at 6 months
N Engl J Med 2003;349(9):831-836.
19. Dexamasone 40mg IVA QD x4 days
Every 28 days for 6 cycles
Prednisone at 0.25 mg/kg/day PO
Plt < 20X10^9 /L
Bleeding symptoms related to thrombocytopenia
CR - >150X10^9/L
PR - 50X10^9/L ~ 150X10^9/L
MR( minimal response)
20X10^9/L ~ 50X10^9/L (Monocenter: 1996 and June 2000 at the
Haematology Department of the University La Sapienza of
Rome,Hospital Policlinico Umberto I Italy)
30X10^9/L ~ 50X10^9/L (GIMEMAmulticenter pilot study)
NR( no response)
<20X10^9/L (Monocenter)
<20X10^9/L (GIMEMAmulticenter pilot study)
Blood 2007;109(4):1401-1407.
20. Monocenter trial
RFS:
97% a 6 months
t
90% a 1 5 months
t
58% a 50 months
t
RFS
RFS:
Cycle 6 : 94% a 1 5 months
t
RFS Cycle 3-4-5: 84% a 1 5 months
t
according to
cycles
Blood 2007;109(4):1401-1407.
22. GIMEMAmulticenter pilot
study
RFS:
< 1 8y/o: 96% a 1 5 ms
t
> = 1 8y/o: 60% a 1 5 ms
t
RFS:
CR : 87% a 1 5ms
t
PR+ M R:65% a 1 5ms
t
Blood 2007;109(4):1401-1407.
23. Recommend
Splenectomy for patients failing steroid (1B)
The only treatment for sustained remission off all
treatment at 1 year and beyond in a high
proportion of patients
Deferred for at least 6 months after diagnosis
Blood. 2010;115(2):168-186.
Against further treatment in asymptomatic
patients after splenectomy with platelet count
>30x10^9/L (1C)
Blood.2011;117(16):4190-4207
28. Gooup 0: spontaneous remission
Group 1: response to steroid,danazol,colchicine,
vinblastin, rituximab,interferon
Group 2:response to oral cyclophosphmide,
azathioprine,cyclosproine
Group 3: response to IV cyclophosphmide or C/T
Blood 2004;104(4):956-960.
31. Both offer similar efficacy (1C)
Blood 2004;104(9):2623-2634
Surg Endosc 2006;20(8):1208-1213.
2010 CDC recommend
pneumococcal and meningococcal vaccination
for elective splenectomy
One dose of H influenzae type b is not
contraindicated before splenectomy
Blood 2007;109(4):1401-1407.
32. Recommend
TPO agonists for risk of bleeding who relapse after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy (1B)
Suggest
TPO for risk of bleeding who failed one line of
therapy (steroid or IVIG) and s/p no splenectomy
(2C)
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy) (2C)
34. 50 mg or placebo PO once daily for
6 weeks
Increased from 50 mg to
75 mg after 3 weeks in patients with
platelet counts less than 50 000 per
μL
Lancet 2009;373(9664):
641-648.
40. US FDA approval: chronic ITP with insufficient
response to steroid, IVIG , or splenectomy
Thrombocytopenia recurs or worsen if
suddenly abrupted
Increased risk of portal venous thrombosis in
chronic liver disease
Hematol 2010;47(3):289-298.
Increased marrow reticulin fibrosis in 10/271
in the romiplostin trials
Blood 2009;114(18):3748-3756.
41. Weekly infusion of 375mg/m2 for 4 weeks in 16/19
studies Ann Intern Med 2007;146(1):25-33.
42. 30% at one year
J Support Oncol 2007;5 4 suppl 2:82-84. 2007.
9/26 (35%) had long-term response
median follow-up of 57 months (range 39–69)
11/26 (42%) did not necessitate further
therapy
Eur J Haematol 2008;81(3):165-169.
43. Treat newly diagnosed patients with platelet count
<30x10^9/L
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
Splenectomy for patients failing steroid
Against further treatment in asymptomatic patients
after splenectomy with platelet count >30x10^9/L
TPO agonists for risk of bleeding who relpase after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy)
44. Treat newly diagnosed patients with platelet count
<30x10^9/L
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
Splenectomy for patients failing steroid
Against further treatment in asymptomatic patients
after splenectomy with platelet count >30x10^9/L
TPO agonists for risk of bleeding who relpase after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy)
45. Treat newly diagnosed patients with platelet count
<30x10^9/L
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
Splenectomy for patients failing steroid
Against further treatment in asymptomatic patients
after splenectomy with platelet count >30x10^9/L
TPO agonists for risk of bleeding who relpase after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy)
46. Treat newly diagnosed patients with platelet count
<30x10^9/L
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
Splenectomy for patients failing steroid
Against further treatment in asymptomatic patients
after splenectomy with platelet count >30x10^9/L
TPO agonists for risk of bleeding who relpase after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy)
47. Treat newly diagnosed patients with platelet count
<30x10^9/L
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
Splenectomy for patients failing steroid
Against further treatment in asymptomatic patients
after splenectomy with platelet count >30x10^9/L
TPO agonists for risk of bleeding who relpase after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy)
48. Treat newly diagnosed patients with platelet count
<30x10^9/L
Longer courses of steroid are preferred than short
courses of steroid or IVIG as first-line treatment
Splenectomy for patients failing steroid
Against further treatment in asymptomatic patients
after splenectomy with platelet count >30x10^9/L
TPO agonists for risk of bleeding who relpase after
splenectomy or who have contraindication to
splenectomy failing at least one other therapy
Rituximab for risk of bleeding who failed one line of
therapy (steroid , IVIG or splenectomy)
