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1、Benign Hematology Update: ASH, ISTH, and the Literature 2013,Craig M Kessler, MD, MACP Professor of Medicine and Pathology Lombardi Comprehensive Cancer Center Georgetown University Medical Center Washington, DC,Disclosures,Research- Amgen, Baxter, Bayer, Biogen, Esai, Grifols, NovoNordisk, Octaphar
2、maAdvisory Boards-Amgen, Baxter, Bayer, Biogen, Esai, Grifols, NovoNordisk, OctapharmaStock- Not applicable Employment Not applicable Speakers Bureau Not applicable,Topics,Autoimmune thrombocytopenia Target specific oral anticoagulation New antiplatelet agents New developments in von Willebrand dise
3、ase Advances in the treatment of sickle cell anemia Miscellaneous,Pathophysiology of Immune Thrombocytopenic Purpura,Phagocyte-mediated accelerated clearance of antiplatelet AB coated platelets in the RES Dysregulated T-cell function Direct cytotoxicity against megakaryocytes and platelets T-helper
4、cell support for biosynthesis of Abs by B-cells Abnormal number and function of T-regs Suboptimal platelet production,What is the best approach to corticosteroids for de novo ITP?,Abs 325: A Randomized Trial Of Daily Prednisone Versus Pulsed Dexamethasone In Treatment of Nave Patients With Idiopathi
5、c Thrombocytopenic Purpura Matsche J et al,Week 1: All pts received prednisone (1 mg/kg/d) followed by a 1:1 randomization between daily prednisone and pulsed dexamethasonePrednisone given at 1 mg/kg/d; after remission dose tapered 19 weeks to maintenance dose 25 mg/d at wk 13 and 50x109/l) in ITP p
6、ts receiving daily prednisone versus pulsed dexamethasone,No statistically significant difference in time to remission (p=0.55)Remission duration significantly longer with dex vs prednisone (p=0.0139)Median tx duration = 85 d (range: 28 153) for pred; Median tx cycles 5 (range: 3 7) for dex Median c
7、umulative cortisol equivalent dose = 15.780 mg for pred; and 34.560 mg for dexNo difference in Grade 3 or 4 bleeding events No difference in Grade 3 or 4 adverse events: 1 pt on pred (hypertension) and 2 pts on dex (hyperglycemia, hypokalemia).,% Control Megakaryocytes,Suppression of Megakaryocyte M
8、aturation and Platelet Production by ITP Plasma,100,75,50,25,0,ITP-1,ITP-2,ITP-3,ITP-4,ITP-5,ITP-6,ITP-7,ITP-8,ITP-9,ITP-10,ITP-11,ITP-12,McMillan R, et al. Blood. 2004;103:1364-1369.,Heterogeneous responses in vitro: Anti-platelet ABs affect megakaryocytes and circulating platelets,How Does Rituxim
9、ab Affect ITP Outcome?,Abs 449: Rituximab As Second Line Treatment For Adult Immune Thrombocytopenia (ITP): A Multicentre, Randomized, Double Blind, Placebo-Controlled Study The Ritp Study Ghanima W et al,First randomized placebo-controlled, double blind study to assess both short and long-term effi
10、cacy and safety of RTX in steroid-unresponsive ITP Pts randomized to 4 weekly infusions of 375mg/m2 RTX or placeboSteroids allowed throughout the studyMain inclusion criteria: 1- unsplenectomized with primary ITP; platelets 2 wks or relapse during steroid-tapering/discontinuation,Abs 449: Rituximab
11、As Second Line TreatmentFor Adult Immune Thrombocytopenia (ITP): A Multicentre, Randomized, Double Blind, Placebo-Controlled Study The Ritp Study Ghanima W et al,Abs 449: Rituximab As Second Line TreatmentFor Adult Immune Thrombocytopenia (ITP): A Multicentre, Randomized, Double Blind, Placebo-Contr
12、olled Study The Ritp Study Ghanima W et al,Time to Complete Response (days) Placebo Rituximab,Per Cent of Patients NOT Achieving Complete Response,RTX did not reduce the rate of overall treatment failure Lower rate of splenectomy in the RTX-arm RTX induced significantly higher rate of CR at 24 wks,D
13、o TPO-RAs Enhance Rituximab Effectiveness?,Abs 329: Recombinant Human TPO and Rituximab vs Rituximab Monotherapy in Corticosteroid-Resistant Primary ITP: a Multicenter Randomized Controlled Study Xiu M et al,Characteristics and result of RTX group and rhTPO plus RTX,Kaplan-Meier plot of time to rela
14、pse in patients achieving response or complete response,RTX + rhTPO yields shorter time to response vs RTX only Combination extended time to relapse,1. Harker LA. Br J Haematol. 1970;19:95-104. 2. Branehg I, et al. Br J Haematol. 1974;27:127-143. 3. Stoll D, et al. Blood. 1985;65:584-588. 4. Ballem PJ, et al. J Clin Invest. 1987;80:33-40.,Platelet Production in ITP: Decreased Turnover Equates to Impaired Thrombopoiesis,
