Prognosis and risk factors of chronicity in childhood idiopathic thrombocytopenic purpura: a single-center experience

Abstract

Objective: In previous studies, chronicity risk factors for idiopathic thrombocytopenic purpura (ITP) are unclear. This study aimed to evaluate the outcome of children with ITP and determine the chronicity risk factors. Methods: This study retrospectively examined the demographics, laboratories, outcome, and chronicity risk factors among sixty children with ITP and obtained the data from the computer system. We analyzed demographics, treatment, and laboratory risk factors for chronic ITP by IBM SPSS and used binary logistic regression analysis. Results: Of 60 children with ITP, 32 (53.3%) had acute, 25 (41.7%) had chronic, and 3 (5%) had persistent ITP. Demographics, laboratories (age <4 years, thrombocyte count at diagnosis, serum LDH, neutrophil count, mean platelet volume, status and grade of bleeding, infection in the last month) were unrelated to chronic ITP. As a new finding, loss of treatment response rates predicts chronicity in both univariate OR [2.56 (1.25 – 5.25)](p=0.01) and multivariate analysis OR [3.873 (1.488–10.08](p=0.006). Among second-line therapies, eltrombopag (n=6) achieved a durable response of thrombocyte count for more than 50.000/mm³ in five. However, two required the cessation of treatment two due to renal failure. Of two splenectomized patients, one could not achieve remission. Conclusion: Lower platelet counts (<20.000/mm³), younger age, male gender, and initial treatment regimens (IVIG, steroid, IVIG plus steroid) did not influence chronicity in our study. We suggest that loss of response rates predicts chronicity as a new factor.

Keywords

• Idiopathic Thrombocytopenic Purpura
• Chronic
• Children

References

1. Miltiadous O, Hou M, Bussel J.B. Identifying and treating refractory ITP: difficulty in diagnosis and role of combination treatment. Blood. 2020;135(7):472-490. https://doi.org/ 10.1182/blood.2019003599. 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(1). https://doi.org/10.1002/pbc.26736.
2. Jaime-Pérez JC, Aguilar-Calderón P, Jiménez-Castillo RA, Ramos-Dávila EM, Salazar-Cavazos L, Gómez-Almaguer D. Treatment outcomes and chronicity predictors for primary immune thrombocytopenia: 10-year data from an academic center. Ann Hematol. 2020;99(11):2513-2520. https://doi.org/10.1007/s00277-020-04257-2.
3. Fernández-Plaza S, González de Pablo J, Gálvez E, Zubicaray J, Guillén M, Sevilla J, et al. Variables related to chronic immune thrombocytopenia: experience from a single center and comparison to a meta-analysis. Eur J Pediatr. 2021;180(7):2075-2081. https://doi.org/10.1007/s00431-021-03990-8.
4. Glanz J, France E, Xu S, Hayes T, Hambidge S. A population-based, multisite cohort study of the predictors of chronic idiopathic thrombocytopenic purpura in children. Pediatrics. 2008;121: e506–e512   https://doi.org/10.1542/peds.2007-1129.
5. Bruin M, Bearings M, Uiterwaal C, Révész T, Bode L, Wiesman ME et al. Platelet count, previous infection and FCGR2B genotype predict development of chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood: results of a prospective study. Br J Haematol. 2004; 127:561–567. https://doi.org/10.1111/j.1365-2141.2004.05235
6. Heitink-Pollé KM, Nijsten J, Boonacker CW, de Haas M, Bruin MC. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis. Blood. 2014; 124:3295–3307. https://doi.org/10.1182/blood-2014-04-570127. 
7. Emilia Parodi, Giovanna Russo, Piero Farruggia, Lucia D Notarangelo, Maria T Giraudo, Margherita Nardi, “AIEOP-ITP Study Group”. Management strategies for newly diagnosed immune thrombocytopenia in Italian AIEOP Centres: do we overtreat? Data from a multicentre, prospective cohort study. Blood Transfus 2020;18(5):396-405. https://doi.org/10.2450/2020.0041-20.
8. Tamminga R, Berchtold W, Bruin M, Buchanan GR, Kühne T. Possible lower rate of chronic ITP after IVIG for acute childhood ITP an analysis from registry I of the Intercontinental Cooperative ITP Study Group (ICIS). Br J Haematol 2009; 146:180–184. https://doi.org/10.1111/j.1365-2141.2009.07743.x.

9. Heitink-Pollé KMJ, Uiterwaal CSPM, Porcelijn L, Tamminga RYJ, Smiers FJ, van Woerden N, et al. Investigators Intravenous immunoglobulin versus observation in childhood immune thrombocytopenia: a randomized controlled trial. Blood 2018;132: 883–891. https://doi.org/10.1182/blood-2018-02-830844.
10. Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, Cuker A, Despotovic JM, George JN, Grace RF, Kühne T, Kuter DJ, Lim W, McCrae KR, Pruitt B, Shimanek H, Vesely SK. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866. https://doi: 10.1182/bloodadvances.2019000966.
11. Donato H, Picón A, Rapetti MC, Rosso A, Schvartzman G, Drozdowski C, Di Santo JJ. Splenectomy and spontaneous remission in children with chronic idiopathic thrombocytopenic purpura. Pediatr Blood Cancer. 2006 Oct 15;47(5 Suppl):737-9. https://doi: 10.1002/pbc.20982.
12. Deel M, Kong M, Cross K, Bertolone S. Absolute lymphocyte counts as prognostic indicators for immune thrombocytopenia outcomes in children. Pediatr Blood Cancer 2013; 60:1967–1974.   https://doi.org/10.1002/pbc.24628.
13. Ahmed I, Rajpurkar M, Thomas R, Chitlur M. Initial lymphocyte count and the development of persistent/chronic immune thrombocytopenic purpura. Pediatr Blood Cancer. 2010; 55:508–511. https://doi.org/10.1002/pbc.22570. 
14. Demircioglu F, Saygi M, Yilmaz S, Oren H, Irken G. Clinical features, treatment responses, and outcome of children with idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol. 2009;26(7):526–532. https://doi.org 10.108/ 08880010903044540. 
15. Grace RF, Despotovic JM, Bennett CM, Bussel JB, Neier M, Neunert C, Crary SE, Pastore YD, Klaassen RJ, Rothman JA, Hege K, Breakey VR, Rose MJ, Shimano KA, Buchanan GR, Geddis A, Haley KM, Lorenzana A, Thompson A, Jeng M, Neufeld EJ, Brown T, Forbes PW, Lambert MP. Physician decision making in selection of second-line treatments in immune thrombocytopenia in children. Am J Hematol. 2018;93(7):882-888. https://doi: 10.1002/ajh.25110.