ITP ASH Guideline

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  • 這篇指引建議的證據等級
  • 新診斷 ITP: 從診斷起小於 3 個月 持續性 ITP: 從診斷起 3 個月到 12 個月 慢性 ITP: 超過 12 個月
  • 建議要測 HIV 另外如果有血小板低下以外的其他異常還是要考慮作骨髓檢查
  • 次發性血小板低下的原因
  • 只有大約 50% 到 70% 的 ITP 其抗血小板抗體陽性
  • 血小板低於 3 萬才開始需要治療 長期 ( 使用到 1 個月 ) 的類固醇會比短期的類固醇加上免疫球蛋白來得好
  • 在 60 歲以上如果血小板低於 3 萬其在第 5 年的致命出血機率大約是 50%
  • 長期 ( 使用到 1 個月 ) 的類固醇會比短期的類固醇加上免疫球蛋白來得好
  • 使用高劑量 MTP + 免疫球蛋白治療 ITP
  • 使用點滴的 MTP 之後換成口服的類固醇效果並沒有比較差
  • 高劑量的類固醇每天 40mg dexamethasone 連續使用 4 天可治療 ITP
  • 在治療後的第 10 天如果血小板低於 90000/L ,則有 70% 的機會復發
  • 使用高劑量 Dexamethasone 治療的效果
  • 無復發存活率相當不錯
  • 年紀小於 18 歲其完全緩解率高達 86% ,比大於 18 歲的完全緩解率 (66%) 來得高
  • 年紀小於 18 歲的癒後較好
  • 如果類固醇沒有效之後才會考慮切除脾臟
  • 慢性 ITP 切除脾臟後的成效
  • 慢性 ITP 在切除脾臟之前的治療
  • 在切除脾臟之後真正還是沒效的只有 2.7%
  • 如果切除脾臟之後還是沒效可以考慮免疫抑制劑,口服或點滴化療藥
  • 在切除脾臟之後還是要施打疫苗以避免感染
  • TPO agonist 比較建議如果切除脾臟之後還是沒效再給
  • 其他可以考慮的治療
  • Eltrombobag 治療 ITP 的臨床試驗
  • Eltrombobag 可以增加血小板的數量
  • Eltrombobag 可以增加血小板的數量
  • Romiplostim 的劑量是可以調整的
  • Romiplostim 可以增加血小板的數量
  • 沒有切除脾臟使用 Romiplostim 的效果比較好
  • 在使用類固醇,免疫球蛋白還有切除脾臟之後沒有效才需要考慮 TPO agnosit
  • Rituximab 治療 ITP 的效果
  • 只有 3 成有長期的治療效果
  • ITP ASH Guideline

    1. 1. ITP in the adultBlood.2011;117(16):4190-4207 Presentor: 周益聖 I nstructor: 蕭樑材
    2. 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. 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. 4.  Newly diagnosed: diagnosis to 3 months  Persistent: 3 to 12 months from diagnosis  Chronic: more than 12 months Newly 12Diagnosis diagnosed 3 months Persistent Chronic months Blood. 2009;113(11):2386-2393.
    5. 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. 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. 7. Flow Cytometry using donor platelets asSPRCA ( Solid phase red cell adherence target cells detects detects autoAb inassay)for plasma anti-platelet Ab 70 %(31/44) in ITPSensitivity: 50% (22/44), J Chin Med Assoc 2006;69(12):569-574.Specificty:100%
    8. 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. 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. 10. 72 pts : steroid only ( 1mg/ kg/ day) 9 pts: high dose IVIG (0.5-2g/kg) 28pts: combined both 5 pts: conservativeCR:>100X10^9/LPR: 30X10^9/L ~ 100X10^9/L Haematologica 2006;91(8):1041-1045.
    11. 11. Plt> 30X10^9/L:CR:>100X10^9/L 86% at 5 yearsPR: 30X10^9/L ~ 100X10^9/L PR +CR:86% @ 5 yrs CR:61% @ 5 yrs Haematologica 2006;91(8):1041-1045.
    12. 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 bleedingArch Intern Med 2000;160(11):1630-1638.
    13. 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
    14. 14. Plt<20x10^9/L HDMP 15mg/IVIG 0.7g/Kg/ Kg/dayday D1-3D1-3 Daily dose<1g Prednisolone (10mg) 1mg/Kg/day Lancet 2002;359(9300):23-29. D4-21
    15. 15. Longer time to loss of responseLancet 2002;359(9300):23-29.
    16. 16. Lancet2002;359(9300):23-2
    17. 17. Dex 40mg/day D1-4 -Dex 40mg/day D1-4 -Pred 15mg maintianN Engl J Med2003;349(9):831-836.
    18. 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. 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. 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.
    21. 21. Blood 2007;109(4):1401-1407.
    22. 22. GIMEMAmulticenter pilotstudyRFS:< 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. 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
    24. 24. Br J Haematol 2003;120(6):1079-1088.
    25. 25. Br J Haematol 2003;120(6):1079-1088.
    26. 26. Trulyrefractorycases postsplenectomy:5/183(2.7%) Br J Haematol 2003;120(6):1079-1088.
    27. 27. Br J Haematol 2003;120(6):1079-1088.
    28. 28. Gooup 0: spontaneous remissionGroup 1: response to steroid,danazol,colchicine,vinblastin, rituximab,interferonGroup 2:response to oral cyclophosphmide,azathioprine,cyclosproineGroup 3: response to IV cyclophosphmide or C/T Blood 2004;104(4):956-960.
    29. 29. Blood 2004;104(4):956-960.
    30. 30. Blood 2004;104(4):956-960.
    31. 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. 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)
    33. 33. Blood.2011;117(16):4190-4207
    34. 34. 50 mg or placebo PO once daily for6 weeksIncreased from 50 mg to75 mg after 3 weeks in patients withplatelet counts less than 50 000 perμL Lancet 2009;373(9664): 641-648.
    35. 35. Lancet 2009;373(9664): 641-648.
    36. 36. Lancet 2009;373(9664):641-648.
    37. 37. Lancet 2008;371(9610): 395-403. Splenectomised:3ug/Kg Non-splenectomised:2ug/SC QW for 24 weeks KgTo keep Plt 50×10 ⁹ /Lto 200×10 ⁹ /L.
    38. 38. Lancet 2008;371(9610): 395-403.
    39. 39. Lancet 2008;371(9610): 395-403.
    40. 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. 41.  Weekly infusion of 375mg/m2 for 4 weeks in 16/19 studies Ann Intern Med 2007;146(1):25-33.
    42. 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. 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. 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. 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. 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. 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. 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)
    49. 49.  Thanks for your attention!

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