ITP in the adultBlood.2011;117(16):4190-4207

Presentor: 周益聖Instructor: 蕭樑材

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

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

Newly diagnosed: diagnosis to 3 months Persistent: 3 to 12 months from diagnosis Chronic: more than 12 months

3 months12

monthsDiagnosis

Newly diagnosed Persistent Chronic

Blood. 2009;113(11):2386-2393.

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

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

Flow Cytometry using donor platelets as target cells detects detects autoAb in 70 %(31/44) in ITP

SPRCA ( Solid phase red cell adherence assay)for plasma anti-platelet AbSensitivity: 50% (22/44), Specificty:100% J Chin Med Assoc 2006;69(12):569-574.

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.(1.5g/Kg)

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

Haematologica 2006;91(8):1041-1045.

CR:>100X10^9/LPR: 30X10^9/L ~ 100X10^9/L

72 pts : steroid only ( 1mg/ kg/ day)9 pts: high dose IVIG (0.5-2g/kg)28pts: combined both5 pts: conservative

Plt> 30X10^9/L:86% at 5 yearsCR:>100X10^9/L

PR: 30X10^9/L ~ 100X10^9/L

CR:61% @ 5 yrs

PR +CR:86% @ 5 yrs

Haematologica 2006;91(8):1041-1045.

47.8% in aged >60 yrs @ 5 yrs

2.2% in aged <40 yrs @ 5 yrs

Fatal bleeding

76% in aged >60 years at 2 years

Plt<30x10^9/L

Non-fatal bleeding

Arch Intern Med 2000;160(11):1630-1638.

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

IVIG 0.7g/Kg/dayD1-3

Plt<20x10^9/L

HDMP 15mg/Kg/dayD1-3Daily dose<1g

Prednisolone(10mg) 1mg/Kg/dayD4-21

Lancet 2002;359(9300):23-29.

Lancet 2002;359(9300):23-29.

Longer time to loss of response

Lancet 2002;359(9300):23-29.

Dex40mg/dayD1-4

-Dex40mg/dayD1-4-Pred 15mg maintian

N Engl J Med 2003;349(9):831-836.

-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.

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.

RFS

RFS according to cycles

Monocenter trial

RFS:97% at 6 months90% at 15 months58% at 50 months

RFS:Cycle 6 : 94% at 15 monthsCycle 3-4-5: 84% at 15 months

Blood 2007;109(4):1401-1407.

Blood 2007;109(4):1401-1407.

RFS:<18y/o: 96% at 15 ms>=18y/o: 60% at 15 ms

RFS:CR : 87% at 15msPR+MR:65% at 15ms

GIMEMAmulticenter pilot study

Blood 2007;109(4):1401-1407.

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

Br J Haematol 2003;120(6):1079-1088.

Br J Haematol 2003;120(6):1079-1088.

Br J Haematol 2003;120(6):1079-1088.

Truly refractory cases post splenectomy : 5/183(2.7%)

Br J Haematol 2003;120(6):1079-1088.

Blood 2004;104(4):956-960.

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.

Blood 2004;104(4):956-960.

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.

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)

Blood.2011;117(16):4190-4207

Lancet 2009;373(9664):641-648.

50 mg or placebo PO once daily for 6 weeks

Increased from 50 mg to75 mg after 3 weeks in patients with platelet counts less than 50 000 per μL

Lancet 2009;373(9664): 641-648.

Lancet 2009;373(9664):641-648.

Lancet 2008;371(9610): 395-403.

SC QW for 24 weeks

To keep Plt 50×10⁹/L to 200×10⁹/L.

Splenectomised:3ug/Kg

Non-splenectomised:2ug/Kg

Lancet 2008;371(9610): 395-403.

Lancet 2008;371(9610): 395-403.

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.

Weekly infusion of 375mg/m2 for 4 weeks in 16/19 studies Ann Intern Med 2007;146(1):25-33.

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.

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)

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)

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)

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)

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)

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)

Thanks for your attention!