Journal of Yeungnam Medical Science

Yeungnam University College of Medicine, Yeungnam University Institute Medical Science (영남대 의대 학술지 편집위원회)
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Advances in management of pediatric chronic immune thrombocytopenia: a narrative review

  • Jae Min Lee (Department of Pediatrics, Yeungnam University College of Medicine)
  • Received : 2022.10.12
  • Accepted : 2022.11.09
  • Published : 2023.07.31
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초록

Immune thrombocytopenia (ITP) is a disease in which thrombocytopenia occurs because of immune-mediated platelet destruction and decreased platelet production. Although many pediatric patients with ITP experience spontaneous remission or reach remission within 12 months of first-line therapy, approximately 20% progress to chronic ITP. Patients who do not respond to first-line treatment or experience frequent relapses are of great concern to physicians. This review summarizes recent treatments for second-line treatment of pediatric chronic ITP.

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참고문헌

  1. Lim JH, Kim YK, Min SH, Kim SW, Lee YH, Lee JM. Epidemiology and viral etiology of pediatric immune thrombocytopenia through Korean public health data analysis. J Clin Med 2021;10:1356.
  2. Cooper N, Ghanima W. Immune thrombocytopenia. N Engl J Med 2019;381:945-55. https://doi.org/10.1056/NEJMcp1810479
  3. Bennett CM, Neunert C, Grace RF, Buchanan G, Imbach P, Vesely SK, et al. Predictors of remission in children with newly diagnosed immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group Registry II participants. Pediatr Blood Cancer 2018;65:e26736.
  4. Grainger JD, Rees JL, Reeves M, Bolton-Maggs PH. Changing trends in the UK management of childhood ITP. Arch Dis Child 2012;97:8-11. https://doi.org/10.1136/adc.2010.184234
  5. Grimaldi-Bensouda L, Nordon C, Leblanc T, Abenhaim L, Allali S, Armari-Alla C, et al. Childhood immune thrombocytopenia: a nationwide cohort study on condition management and outcomes. Pediatr Blood Cancer 2017;64:e26389.
  6. Kuhne T, Imbach P, Bolton-Maggs PH, Berchtold W, Blanchette V, Buchanan GR, et al. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. Lancet 2001;358:2122-5. https://doi.org/10.1016/S0140-6736(01)07219-1
  7. Lilleyman JS. Intracranial haemorrhage in idiopathic thrombocytopenic purpura: Paediatric Haematology Forum of the British Society for Haematology. Arch Dis Child 1994;71:251-3. https://doi.org/10.1136/adc.71.3.251
  8. Iyori H, Bessho F, Ookawa H, Konishi S, Shirahata A, Miyazaki S, et al. Intracranial hemorrhage in children with immune thrombocytopenic purpura. Ann Hematol 2000;79:691-5. https://doi.org/10.1007/s002770000219
  9. Neunert CE, Buchanan GR, Imbach P, Bolton-Maggs PH, Bennett CM, Neufeld EJ, et al. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008;112:4003-8.
  10. Neunert CE, Buchanan GR, Imbach P, Bolton-Maggs PH, Bennett CM, Neufeld E, et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS). Blood 2013;121:4457-62. https://doi.org/10.1182/blood-2012-12-466375
  11. Choudhary DR, Naithani R, Mahapatra M, Kumar R, Mishra P, Saxena R. Intracranial hemorrhage in childhood immune thrombocytopenic purpura. Pediatr Blood Cancer 2009;52:529-31. https://doi.org/10.1002/pbc.21728
  12. Psaila B, Petrovic A, Page LK, Menell J, Schonholz M, Bussel JB. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood 2009;114:4777-83. https://doi.org/10.1182/blood-2009-04-215525
  13. Elalfy M, Elbarbary N, Khaddah N, Abdelwahab M, El Rashidy F, Hassab H, et al. Intracranial hemorrhage in acute and chronic childhood immune thrombocytopenic purpura over a ten-year period: an Egyptian multicenter study. Acta Haematol 2010;123:59-63. https://doi.org/10.1159/000262293
  14. Jaime-Perez JC, Ramos-Davila EM, Melendez-Flores JD, Gomez-De Leon A, Gomez-Almaguer D. Insights on chronic immune thrombocytopenia pathogenesis: a bench to bedside update. Blood Rev 2021;49:100827.
  15. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization 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. https://doi.org/10.1182/blood-2008-07-162503
  16. Kuhne T, Berchtold W, Michaels LA, Wu R, Donato H, Espina B, et al. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematologica 2011;96:1831-7. https://doi.org/10.3324/haematol.2011.050799
  17. Schifferli A, Holbro A, Chitlur M, Coslovsky M, Imbach P, Donato H, et al. A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up. Am J Hematol 2018;93:751-9. https://doi.org/10.1002/ajh.25086
  18. Jung JY, O AR, Kim JK, Park M. Clinical course and prognostic factors of childhood immune thrombocytopenia: single center experience of 10 years. Korean J Pediatr 2016;59:335-40. https://doi.org/10.3345/kjp.2016.59.8.335
  19. Kim CY, Lee EH, Yoon HS. High remission rate of chronic immune thrombocytopenia in children: result of 20-year follow-up. Yonsei Med J 2016;57:127-31. https://doi.org/10.3349/ymj.2016.57.1.127
  20. Shim YJ, Kim UH, Suh JK, Lee KS. Natural course of childhood chronic immune thrombocytopenia using the revised terminology and definitions of the international working group: a single center experience. Blood Res 2014;49:187-91. https://doi.org/10.5045/br.2014.49.3.187
  21. Kim JY. Diagnostic approach of childhood immune thrombocytopenia. Clin Pediatr Hematol Oncol 2018;25:10-6. https://doi.org/10.15264/cpho.2018.25.1.10
  22. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117:4190-207. https://doi.org/10.1182/blood-2010-08-302984
  23. Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019;3:3780-817. https://doi.org/10.1182/bloodadvances.2019000812
  24. Nomura S. Advances in diagnosis and treatments for immune thrombocytopenia. Clin Med Insights Blood Disord 2016;9:15-22. https://doi.org/10.4137/CMBD.S39643
  25. Mitchell WB, Pinheiro MP, Boulad N, Kaplan D, Edison MN, Psaila B, et al. Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia. Am J Hematol 2014;89:E228-34. https://doi.org/10.1002/ajh.23832
  26. Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019;3:3829-66. https://doi.org/10.1182/bloodadvances.2019000966
  27. Wire MB, Bruce J, Gauvin J, Pendry CJ, McGuire S, Qian Y, et al. A randomized, open-label, 5-period, balanced crossover study to evaluate the relative bioavailability of eltrombopag powder for oral suspension (PfOS) and tablet formulations and the effect of a high-calcium meal on eltrombopag pharmacokinetics when administered with or 2 hours before or after PfOS. Clin Ther 2012;34:699-709. https://doi.org/10.1016/j.clinthera.2012.01.011
  28. Deng Y, Madatian A, Wire MB, Bowen C, Park JW, Williams D, et al. Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects. Drug Metab Dispos 2011;39:1734-46. https://doi.org/10.1124/dmd.111.040170
  29. Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet 2015;386:1649-58. https://doi.org/10.1016/S0140-6736(15)61107-2
  30. Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, et al. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol 2015;2:e315-25. https://doi.org/10.1016/S2352-3026(15)00114-3
  31. Giordano P, Lassandro G, Barone A, Cesaro S, Fotzi I, Giona F, et al. Use of eltrombopag in children with chronic immune thrombocytopenia (ITP): a real life retrospective multicenter experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Front Med (Lausanne) 2020;7:66.
  32. Bussel JB, Buchanan GR, Nugent DJ, Gnarra DJ, Bomgaars LR, Blanchette VS, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood 2011;118:28-36. https://doi.org/10.1182/blood-2010-10-313908
  33. Bussel JB, Hsieh L, Buchanan GR, Stine K, Kalpatthi R, Gnarra DJ, et al. Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatr Blood Cancer 2015;62:208-13. https://doi.org/10.1002/pbc.25136
  34. Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet 2016;388:45-54. https://doi.org/10.1016/S0140-6736(16)00279-8
  35. Neunert CE, Rose MJ. Romiplostim for the management of pediatric immune thrombocytopenia: drug development and current practice. Blood Adv 2019;3:1907-15. https://doi.org/10.1182/bloodadvances.2019000279
  36. Newland A, Godeau B, Priego V, Viallard JF, Lopez Fernandez MF, Orejudos A, et al. Remission and platelet responses with romiplostim in primary immune thrombocytopenia: final results from a phase 2 study. Br J Haematol 2016;172:262-73. https://doi.org/10.1111/bjh.13827
  37. Kuter DJ, Newland A, Chong BH, Rodeghiero F, Romero MT, Pabinger I, et al. Romiplostim in adult patients with newly diagnosed or persistent immune thrombocytopenia (ITP) for up to 1 year and in those with chronic ITP for more than 1 year: a subgroup analysis of integrated data from completed romiplostim studies. Br J Haematol 2019;185:503-13. https://doi.org/10.1111/bjh.15803
  38. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 1994;83:435-45. https://doi.org/10.1182/blood.V83.2.435.435
  39. Bennett CM, Rogers ZR, Kinnamon DD, Bussel JB, Mahoney DH, Abshire TC, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood 2006;107:2639-42. https://doi.org/10.1182/blood-2005-08-3518
  40. Parodi E, Rivetti E, Amendola G, Bisogno G, Calabrese R, Farruggia P, et al. Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response. Br JHaematol 2009;144:552-8. https://doi.org/10.1111/j.1365-2141.2008.07487.x
  41. Tamminga RY, Bruin MC. Rituximab treatment for symptomatic chronic ITP. Pediatr Blood Cancer 2006;47(5 Suppl):714-6. https://doi.org/10.1002/pbc.20967
  42. Wang J, Wiley JM, Luddy R, Greenberg J, Feuerstein MA, Bussel JB. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr 2005;146:217-21. https://doi.org/10.1016/j.jpeds.2004.09.004
  43. Kochhar M, Neunert C. Immune thrombocytopenia: a review of upfront treatment strategies. Blood Rev 2021;49:100822.
  44. Patel VL, Mahevas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, et al. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 2012;119:5989-95. https://doi.org/10.1182/blood-2011-11-393975
  45. Zaja F, Baccarani M, Mazza P, Bocchia M, Gugliotta L, Zaccaria A, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 2010;115:2755-62. https://doi.org/10.1182/blood-2009-07-229815
  46. Gudbrandsdottir S, Birgens HS, Frederiksen H, Jensen BA, Jensen MK, Kjeldsen L, et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood 2013;121:1976-81. https://doi.org/10.1182/blood-2012-09-455691
  47. Wang J, Li Y, Wang C, Zhang Y, Gao C, Lang H, et al. Efficacy and safety of the combination treatment of rituximab and dexamethasone for adults with primary immune thrombocytopenia (ITP): a meta-analysis. Biomed Res Int 2018;2018:1316096.
  48. Oved JH, Lee CS, Bussel JB. Treatment of children with persistent and chronic idiopathic thrombocytopenic purpura: 4 infusions of rituximab and three 4-day cycles of dexamethasone. J Pediatr 2017;191:225-31. https://doi.org/10.1016/j.jpeds.2017.08.036
  49. Moss C, Hamilton PJ. Thrombocytopenia in systemic lupus erythematosus responsive to dapsone. BMJ 1988;297:266.
  50. Rodrigo C, Gooneratne L. Dapsone for primary immune thrombocytopenia in adults and children: an evidence-based review. J Thromb Haemost 2013;11:1946-53. https://doi.org/10.1111/jth.12371
  51. Godeau B, Durand JM, Roudot-Thoraval F, Tenneze A, Oksenhendler E, Kaplanski G, et al. Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases. Br J Haematol 1997;97:336-9. https://doi.org/10.1046/j.1365-2141.1997.412687.x
  52. Khera S, Pramanik SK, Yanamandra U, Mishra K, Kapoor R, Das S. Dapsone: an old but effective therapy in pediatric refractory immune thrombocytopenia. Indian J Hematol Blood Transfus 2020;36:690-4. https://doi.org/10.1007/s12288-020-01286-9
  53. Avila ML, Amiri N, Pullenayegum E, Blanchette V, Imbach P, Kuhne T, et al. Long-term outcomes after splenectomy in children with immune thrombocytopenia: an update on the registry data from the Intercontinental Cooperative ITP Study Group. Haematologica 2020;105:2682-5. https://doi.org/10.3324/haematol.2019.236737
  54. Boyle S, White RH, Brunson A, Wun T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood 2013;121:4782-90. https://doi.org/10.1182/blood-2012-12-467068
  55. El-Alfy MS, El-Tawil MM, Shahein N. 5- to 16-year follow-up following splenectomy in chronic immune thrombocytopenic purpura in children. Acta Haematol 2003;110:20-4. https://doi.org/10.1159/000072409
  56. Radaelli F, Faccini P, Goldaniga M, Guggiari E, Pozzoli E, Maiolo AT, et al. Factors predicting response to splenectomy in adult patients with idiopathic thrombocytopenic purpura. Haematologica 2000;85:1040-4.
  57. Hemmila MR, Foley DS, Castle VP, Hirschl RB. The response to splenectomy in pediatric patients with idiopathic thrombocytopenic purpura who fail high-dose intravenous immune globulin. J Pediatr Surg 2000;35:967-72. https://doi.org/10.1053/jpsu.2000.6938
  58. Law C, Marcaccio M, Tam P, Heddle N, Kelton JG. High-dose intravenous immune globulin and the response to splenectomy in patients with idiopathic thrombocytopenic purpura. N Engl J Med 1997;336:1494-8. https://doi.org/10.1056/NEJM199705223362104
  59. Holt D, Brown J, Terrill K, Goldsby R, Meyers RL, Heximer J, et al. Response to intravenous immunoglobulin predicts splenectomy response in children with immune thrombocytopenic purpura. Pediatrics 2003;111:87-90. https://doi.org/10.1542/peds.111.1.87
  60. Grainger JD, Blanchette VS, Grotzinger KM, Roy A, Bussel JB. Health-related quality of life in children with chronic immune thrombocytopenia treated with eltrombopag in the PETIT study. Br J Haematol 2019;185:102-6. https://doi.org/10.1111/bjh.15732
  61. Mathias SD, Li X, Eisen M, Carpenter N, Crosby RD, Blanchette VS. A phase 3, randomized, double-blind, placebo-controlled study to determine the effect of romiplostim on health-related quality of life in children with primary immune thrombocytopenia and associated burden in their parents. Pediatr Blood Cancer 2016;63:1232-7. https://doi.org/10.1002/pbc.25984
  62. Klaassen RJ, Mathias SD, Buchanan G, Bussel J, Deuson R, Young NL, et al. Pilot study of the effect of romiplostim on child health-related quality of life (HRQoL) and parental burden in immune thrombocytopenia (ITP). Pediatr Blood Cancer 2012;58:395-8. https://doi.org/10.1002/pbc.23312