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stemming from antibodies against PEG-rHuMgDF that cross-reacted with endogenous TPO (eTPO), neutralizing its biologic activity. Despite safety concerns raised by autoantibody crossreactivity, the success of the first-generation thrombopoietic growth factors in stimulating platelet production led to the development of a second generation of thrombopoietic growth factors that had no sequence homology with native TPO. Clinical trials with these, the TPO peptide mimetic AMG 531 (also known as Nplate or Romiplostim, Amgen, Thousand Oaks, California) and the nonpeptide mimetic eltrombopag (also known as Promacta, GlaxoSmithKline, Research Triangle Park, North Carolina) have both resulted in dose-dependent increases in platelets in healthy subjects and in significant increases in platelets in patients with chronic ITP. 50 The extensive clinical studies have shown that platelet responses are seen in approximately 80%, a much greater percentage than in other second line studies and the response is maintained while the drugs continue to be administered. They are almost as effective in splenectomized patients as in the nonsplenectomized ones. 51 Recent phase III studies have confirmed the efficacy and safety following long-term usage of both of the currently available products. 52,53 The licenses for these agents vary throughout the world. In some (USA and Canada) the license covers pre-splenectomy use whereas in Europe, this is only covered for patients in whom the surgery is contraindicated. These agents appear to be well tolerated without the formation of autoantibodies that were seen in the studies with the first generation of thrombopoietins. Increases in marrow reticulin have been reported, but these appear to be a reversible phenomenon and not associated with formation of collagen fibrosis. The incidence of increase in marrow reticulin is unknown but is likely to be higher in patients treated with high doses, which should therefore be used with caution. There appears to be no increased incidence of thrombotic events in patients who achieve normal platelet counts compared with those receiving placebo, however, thrombotic events have been reported in patients with other risk factors of cardiovascular disease, and a recent report has shown an increased of venous and arterial thrombo-embolism in any patient with ITP, suggesting that ITP is a pro-thrombotic condition. 54 New developments With the increasing understanding of molecular pathways in ITP and of the aetiology of the disease, more targeted and immune based therapies are under study. Ongoing clinical trials in ITP involve antibodies against the Fc receptor, such as MDX-33, a humanized anti- FcgRI monoclonal, and GMA-161, a humanized anti- FcgRIII monoclonal. 55 Investigation of inhibition of FcR signaling mechanisms is currently under investigation with R788, 56 a small molecule prodrug of the biologically active R406. This is a potent and relatively selective orally available inhibitor of Syk (spleen tyrosine kinase). There are also a number of anti-CD20 monoclonal antibodies attempting to duplicate and improve on the results shown with Rituximab first described by Stasi in 2001. 31 Future treatment options have been recently reviewed. 57 Conclusion While there is general agreement over treatment of the newly presenting adult with ITP, few evidence based studies direct therapy in the relapsed and refractory patient. There is an understanding that the patient should be treated for their clinical state rather than their platelet count but not what second line treatment should be used and in what order. In order to develop a rational approach, an international group produced a consensus report on investigation and management giving (where possible) evidence based advice on treatment pathways. It is hoped that by following such an approach, treatment in the future can be audited and authoritative guidelines developed 7 and the place of the newer treatments understood. References London, United Kingdom, June 9-12, 2011 1. Rodeghiero F, Stasi R, Gernsheimer T, et al. (2009) Standard - ization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009; 113:2386-93. 2. Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94:909-913. 3. Kaye J, Schoonen M, Fryzek J. ITP incidence and mortality in UK general practice database. Haematologica. 2007;92(Suppl 1):280. 4. Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a populationbased cohort of 245 patients. Br J Haematol. 2003;122:966-74. 5. Provan D, Newland AC, et al. British Committee for Standards in Haematology, General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574-96. 6. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3-40. 7. Provan D, Stasi R, Newland AC, et al. (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 115:168-86. 8. Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther M. Clinical guideline update on “Immune thrombocytopenia: an evidence based practiceguideline developed by the American Society of Hematology”. Blood. Feb 16, 2011. (Epub ahead of print as doi:10.1182/blood-2010-08-302984] 9. Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: Pathogenic and clinical diversity. Blood. 2009;113: 6511-21. 10. van Leeuwen EF, van der Ven JT, Engelfriet CP, von dem Borne AE. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood. 1982;59:23-6. 11. Kiefel V, Santoso S, Weisheit M, Mueller-Eckhardt C. Monoclonal antibody--specific immobilization of platelet antigens (MAIPA): a new tool for the identification of platelet-reactive antibodies. Blood. 1987;70:1722-6. 12. McMillan R, Tani P, Millard F, Berchtold P, Renshaw L, Woods VL. Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP. Blood. 1987;70:1040-5. 13. Woods VL, Kurata Y, Montgomery RR, et al. Autoantibodies against platelet glycoprotein Ib in patients with chronic immune thrombocytopenic purpura. Blood. 1984; 64;156-60. 14. Woods VL, Oh EH, Mason D, McMillan R. Autoantibodies against the platelet glycoprotein IIb/IIIa complex in patients with chronic ITP. Blood. 1984;63:368-75. Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 189 |
16 th Congress of the European Hematology Association 15. Branehog I, Kutti J, Weinfeld A. (1974) Platelet survival and platelet production in idiopathic thrombocytopenic purpura (ITP). Br J Haematol. 1974;27:127-43. 16. Harker LA. Thrombokinetics in idiopathic thrombocytopenic purpura. Br J Haematol. 1970;19:95-104. 17. Harker LA, Finch CA. Thrombokinetics in man. J Clin Invest. 1969;48:963-74. 18. Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80:33-40 19. Heyns AdP, Badenhorst PN, Lotter MG, Pieters H, Wessels P, Kotze HF. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ. Blood. 1986;67:86-92. 20. Stoll D, Cines DB, Aster RH, Murphy S. (1985) Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia. Blood. 1985;65:584-88. 21. Li Z, Nardi MA, Karpatkin S. Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia. Blood. 2005;106:572–6. 22. Zhang W, Nardi MA, Borkowsky W, et al. Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood. 2009;113:4086-93. 23. Takahashi T, Yujiri T, Shinohara K, et al. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2004;124:91-6. 24. Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol. 2009;46:S2-14. 25. Cines DB. Pathogenesis of ITP. In Cines DB, Kuter DJ, Newland AC, Provan D, Semple, JW, editors. Immune Thrombocytopenia: The Handbook. 2011ESH Forum Service Editore. P. 77-89 26. Mazzucconi NG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HDDXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura. A GIMEMA experience. Blood. 2007;109:1401-7. 27. Psaila B, Bussel J. Refractory idiopathic thrombocytopenic purpura: current strategies for investigation and management. Br J Haematol. 2008;143:16-26. 28. Provan D, Moss AJ, Newland AC, Bussel JB. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol. 2006 Jan;81(1):19-25. 29. Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood. 2001;97:2549-54. 30. Stasi R, Stipa E, Masi M, et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med. 1995;98:436-42. 31. Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001; 98:952-7. 32. Arnold DM, Dentali F, Crowther MA, et al. Systematic review: Efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med. 2007;146:25-33. 33. Cooper N, Stasi R, Cunningham-Rundles S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;125:232-239. 34. Godeau B, Porcher R, Fain O, et al. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura - results of a prospective multicenter phase 2 study. Blood. 2008;112:999-1004. 35. Zaja F, Baccarani M, Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood. 2010 Feb 3. [Epub ahead of print as doi: 10.1182/blood-2009-07-229815]. 36. Zaja F, Vianelli N, Volpetti S, et al. Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2010 Jun 10. [Epub ahead of print as doi:]. 37. Provan D, Butler T, Evangelista ML, et al. Activity and safety profile of low-dose rituximab for the treatment of autoimmune cytopenias in adults. Haematologica. 2007;92:1695-8. 38. Carson KR, Focosi D, Major EO, et al. Monoclonal antibodyassociated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: A Review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol. 2009;10:816-24. 39. Gottenberg J, Ravaud P, Bardin T, et al. Risk factors of severe infections in patients with rheumatoid arthritis treated with rituximab in the AutoImmunity and Rituximab (AIR) registry. Arthritis Rheum. 2010;62:2625-32. 40. Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: A systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104:2623-34. 41. Wanachiwanawin W, Visudhiphan S, Pinankijagum A, Vatanavicharn S. Therapy of chronic idiopathic thrombocytopenic purpura in adults: Experiences from Thailand. Southeast Asian J Trop Med Public Health. 1993;24(Suppl 1):71-5. 42. Robinette CD, Fraumeni JF. Splenectomy and subsequent mortality in veterans of the 1939-45 war. Lancet .1977;ii:127-9. 43. Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among post-splenectomy patients. J Infect. 2001;43:182-6. 44. Schwartz J, Leber MD, Gillis S, et al. Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol. 2003;72:94-8. 45. McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood. 2004;103:1364-1369. 46. Olsson B, Andersson PO, Jernas M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9:1123-4. 47. Yu J, Heck S, Patel V, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood. 2008;112:1325-8. 48. Sarpatwari A, Provan D, Erquo S, Sobnack R, Tai FWD, Newland AC. Autologous 111 In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry. Br J Haematol. 2010;151:477-87. 49. Molineux G, Newland A. Development of romiplostim for the treatment of patients with chronic immune thrombocytopenia: from bench to bedside. Br J Haematol. 2010;150:9-20. 50. Newland, A. Thrombopoietin mimetic agents in the management of immune thrombocytopenic purpura. Semin Hematol. 2007;44:35-45. 51. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double blind randomized controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. 52. Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and Efficacy of long-term treatment with romiplostim in thrombocytopenic patients with ITP. Blood. 2009;113:2161-71. 53. Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for the management of chronic immune thrombocytopenia (RAISE): a 6 month, randomised phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Erratum in: Lancet. 2011 Jan 29;377 (9763):382. 54. Sarpatwari A, Bennett D, Logie JW, Shukla A, Beach KJ, Newland AC. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010;95:1167-75. 55. Li X, Hou M. Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expt Opin Emerg Drugs. 2008;13:237-54. 56. Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, Bussel JB. Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood. 2009;113:3154-60. 57. Newland AC. Future managements of ITP; in Immune Thrombocytopenia: The Handbook. Cines DB, Kuter DJ, Newland AC, Provan D, Semple JW, editors.2011. ESH Forum Service Editore P. 227-242. | 190 | Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1)
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H e m a t o l o g y E d u c a t i o
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Copyright Information ©2011 by Eur
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Editorial Board Education Book Edit
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Acute lymphoblastic leukemia 1-8 Th
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S. Schnell P. Van Vlierberghe A. Fe
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lineage cells, and in differentiati
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FLT3 mutations The FMS-like tyrosin
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44. Bar-Eli M, Ahuja H, Foti A, Cli
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J.M. Rowe 1,2 C. Ganzel 1 1 Shaare
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treated on the MRC UKALL XII/ECOG29
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asparaginase (PEG), where the Esche
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or higher. It is, however, importan
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25. Bruggemann M, Schrauder A, Raff
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lymphoblastic leukemia: prospective
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such as high white blood cell count
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doxorubicine, there was a trend tow
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of the aging process with respect t
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K.L. Rice 1 M. Buzzai 2 J. Altman 1
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ing FLT3-ITD, wild-type NPM1, or bo
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ciated with gene activation, via th
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leukemia with inv(16) and t(8;21):
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99. Parsons DW, Jones S, Zhang X, e
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abnormalities, some of which are al
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file. 27,31 Thus, the double gene-m
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karyotype represents a distinct gen
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Table 1. Meta-analysis of 23 random
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A recent study by the Center for In
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Patients with HLA-matched related o
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After allogeneic HSCT, an autologou
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A. Bacigalupo Ospedale San Martino,
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Table 2. The effect of HLA mismatch
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References 1. Petersdorf EW, Malkki
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neutrophil and platelet recovery an
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Figure 2. One Year-Overall Survival
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infused on day 21. No serious adver
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W, et al. Effect of graft source on
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TRM was higher for patients who rec
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following a myeloablative preparati
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effect. Surprisingly, none of the p
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nancies. Bone Marrow Transplant. 20
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J.G. Gilles Center for Molecular an
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14C12 was humanized by grafting VH
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Table 1. VWD Classification. VWD Su
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Figure 1. Missense mutations found
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associated with an increased bleedi
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49. Brown SA, Eldridge A, Collins P
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leed. These issues are especially i
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estored function. 43,44 A phase I t
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years’ experience of prophylactic
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J.A. Burger Department of Leukemia,
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chemotaxis, migration across vascul
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Regulatory T cells (T reg), identif
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16. Burger JA, Ghia P, Rosenwald A,
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TE, Nowakowski GS, et al. CD49d exp
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andomized trial demonstrating impro
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Conclusions Chemoimmunotherapy has
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with multiple comorbidities (≥ 2)
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ment was finished in all 100 patien
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Table 2. Treatment recommendation f
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34. Ferrajoli A. The combination of
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to be the source of additional gene
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potential to prevent LSCs from acce
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ABL1 confirms that eradication of d
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65. Fiskus W, Pranpat M, Balasis M,
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alive after 10 years. 11 Hence, CCy
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each arm). A minimal change in myel
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Any discussion about the definition
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H. Kantarjian J. Cortes Leukemia De
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59%; the CCyR rate was 44%. Among p
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ern era of BCR-ABL1 tyrosine kinase
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the hematopoietic system, 10 nor in
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over the period of 6 weeks, demonst
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Data on clonal changes in the blood
Page 148 and 149: 2006 Feb 1;107(3):924-30. 41. Liang
Page 150 and 151: demonstrated that changes in osteob
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Page 156 and 157: ization. In WASP deficiency, lympho
Page 158 and 159: Currently the epistatic relationshi
Page 160 and 161: R. Küppers Institute of Cell Biolo
Page 162 and 163: Figure 1. TNFAIP3 mutation in HL ce
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Page 166 and 167: Hansmann ML, et al. Detection of cl
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Page 172 and 173: 12. Noordijk EM, Carde P, Dupouy N,
Page 174 and 175: A. Sureda Consultant in Haematology
Page 176 and 177: Figure 1. Long-term outcome of pati
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Page 184 and 185: common variants in the regulatory r
Page 186 and 187: against the TPO receptor (cMpl). 61
Page 188 and 189: W.B. Mitchell A.A. Miller J.B. Buss
Page 190 and 191: platelet counts and/or bleeding. Th
Page 192 and 193: Mpl. Cell. 1994;77(7):1117-24. 6. d
Page 194 and 195: ity and mortality associated with t
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Page 202 and 203: cation of molecularly distinct subg
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Page 210 and 211: clear distinction among the lymphom
Page 212 and 213: Treatment strategies in germinal ce
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Page 220 and 221: Table 1. Diffuse Large B cell Lymph
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Page 224 and 225: intensive therapy with curative int
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Page 228 and 229: Balanced translocations In contrast
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Page 242 and 243: Borthakur G, et al. Cause of death
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Page 246 and 247: etween 1995 and 2005. 11 Five hundr
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London, United Kingdom, June 9-12,
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attainment of FDC post DLI. Interes
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myelodysplastic syndromes is associ
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ubiquitous chaperone that promotes
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was thought that they are linked to
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pathologic induction of miR-28 in M
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STATs. Second, levels of HP1 alpha
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72. Irandoust MI, Aarts LH, Roovers
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A.M. Vannucchi Section of Hematolog
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2,559 patients with a diagnosis of
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tant use of aspirin should be caref
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sions at this regard. Based on thes
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in bcr-abl-negative myeloproliferat
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Table 1. Prognostic scoring systems
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Figure 1. Current inhibitors of JAK
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Table 4. A risk-based approach to d
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the flexibility to be adjusted as t
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A. Vacca 1 D. Ribatti 2 1 Departmen
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neovessel building together with MM
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Mevastatin, a specific inhibitor of
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egression of tumor vessels, and app
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diagnosis does not require genetic
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Genetics prognostic tools should be
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sone induction improves outcome of
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Table 1. Conventional chemotherapy
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Novel agents given as consolidation
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dence of peripheral neuropathy, gas
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31. Barlogie B, Tricot G, Anaissie
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Table 1. Major differences between
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first line therapy have shown survi
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transplantation, 7,91 and generally
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methylation characterizes juvenile
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Table 1. Clinical signs of possible
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Table 4. Distribution of CSF involv
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ently results in a less than 5% cum
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90. German-Austrian-Swiss ALL-BFM S
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U. Nowak-Göttl 1 R. Junker 1 A. Kr
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Based on the data obtained from the
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59. Male C, Chait P, Ginsberg JS, e
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Table 1. Characteristic features of
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Table 2. Mutational spectrum of CDA
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megarakaryoblastic leukemia (AMKL)
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R.E. Ware Professor and Vice-Chairm
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protein, cytokines, and soluble adh
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example, improving blood viscosity
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92(9):1266-7. 36. Bensinger TA, Gil
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London, United Kingdom, June 9-12,
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port have also been used. 5 Combina
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Wingard JR, Young J-AH, Boeckh MJ.
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K. Rezvani 1 J. Barrett 2 1 Haemato
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include the childhood infectious il
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Summary Patients undergoing hematop
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Table 1. Key issues. In a retrospec
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invasive method to assess iron over
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stitution but even with optimal sub
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T.M. Hackeng Department of Biochemi
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and inhibits FVIIa, and that the se
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Figure 4. Regulation of coagulation
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T. Baglin Department of Haematology
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Figure 1. Illustration of alternati
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compared with 3.5% in patients with
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49. Hron G, Kollars M, Binder BR, E
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Women receiving vitamin K antagonis
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molecular weight heparin as prophyl
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eral morbidity and mortality. 17-21
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the HOD construct. Furthermore, the
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Goals of future murine studies incl
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F. Noizat-Pirenne C. Tournamille Et
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phenotype. 26 In 2010, we investiga
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ody has been involved in DHTR. 37 T
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antigen. Cases can be encountered d
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S.R. Sloan Harvard Medical School &
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We also analyzed patient databases
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Index of authors Altman J. 27 Bacig
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Cornelissen J. Affiliations to disc
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GlaxoSmithKline (Research Support;
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