İmmun Trombositopenili Hastalarda Dörtlü Tedavi

Amaç:İmmün trombositopeni tedavisinde son yıllarda deksametazon, rituksimab ve siklosporin kombinasyon tedavileri umut verici sonuçlar vermiştir. Bu çalışmada, immün trombositopenide verilen kombinasyon tedavilerinin eltrombopag ile birleştirilmesiyle oluşturulan dörtlü tedavinin hastalardaki yanıtlarının araştırılması amaçlanmıştır. Yöntem:İmmun trombositopeni tanısı almış birinci basamak tedavide steroid, 2.basamak tedavide eltrombopag alan, tam ya da kısmı remisyon sağlanamayan 4 hasta retrospektif olarak aldıkları tedavi ve yanıt oranları açısından değerlendirdi. Sonuç:Relaps /refrakter immün trombositopenisi olan hastalar, eltrombopag tedavisine ek olarak oral deksametazon, oral siklosporin ve intravenöz düşük doz rituksimab ile tedavi edildi. Eltrombopag tedavisine 50 mg/gün dozunda devam edildi. Siklosporin için yükleme dozu verilmedi, haftalık kan siklosporin düzeyi toksisite açısından izlendi ve tedavi 200 ile 400 µg/L'lik bir hedef doza titre edildi. Toksisite kaynaklı ölüm, tedaviye bağlı ciddi advers olaylar veya tedaviye uyumsuzluk gözlenmedi. 6 aylık yanıt oranı %75 idi ve tedavi iyi tolere edildi. Hastalarımızdan iki tanesi halen tam yanıtlı olarak tarafımızca takipli iken bir hastamızda 6.aydan sonra relaps olması nedeniyle splenektomi yapılmış olup halen eltrombopag tedavi ile takiplidir. Yanıtsız olan daha önce splenektomili olan hastamıza ise romiplastim tedavisi uygulandı ancak bu tedaviye de yanıt alınamadı. Hasta klinik çalışmaya dahil edildi. Sonuç:Tedaviye dirençli immün trombositopenili hastalarda dörtlü tedavi kombinasyonunun bir tedavi seçeneği olabileceğini gösteren çalışmamız umut vaad etmektedir.

Anahtar Kelimeler:

immun trombositopeni, eltrombopag, dörtlü tedavi

Quadruple Therapy in Patients with Immune Thrombocytopenia

Objective:In the treatment of immune thrombocytopenia dexamethasone, rituximab, and cyclosporine combination therapies provided promising results in recent years. This study aimed to investigate the responses of patients with quadruple therapy which created by combining combinational therapies given in immune thrombocytopenia with eltrombopag. Method: Four patients diagnosed with immune thrombocytopenia who received steroid in the first-line treatment and eltrombopag in the second-line treatment without achieving complete remission/partial remission were retrospectively evaluated in terms of the treatment they received and response rates. Result:Patients with relapsed/refractory immune thrombocytopenia were treated by oral dexamethasone, oral cyclosporine and intravenous low-dose rituximab in addition to eltrombopag therapy. Eltrombopag treatment was continued at a dose of 50mg/day. No loading dose was given for cyclosporine, weekly blood cyclosporine level was monitored for toxicity and the treatment was titrated to a target dose of 200 to 400 μg/L. No toxicity-induced death, serious treatment-related adverse events, or non-adherence to treatment were observed. The 6-month response rate was 75% and the treatment was well tolerated. Two patients were still followed up by us with a complete response, while one our patient underwent splenectomy because of relapse after 6 months and is still being followed up with eltrombopag therapy. In one our patient, which was unresponsive, romiplastim treatment was applied but there was no response to this treatment either. The patient was referred to a clinical study Conclusion: Our study showing that a combination of quadruple therapy can be a treatment option in patients with treatment-resistant immune thrombocytopenia is promising.

Keywords:

immune thrombocytopenia, eltrombopag, quadruple therapy,

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1. Zhou H, Xu M, Qin P, Zhang H-Y, Yuan C, Zhao H et al. A multicenter randomized open label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP. Blood.2015;125(10):1541-47. doi: 10.1182/blood-2014-06-581868.
2. Çekdemir D, Güvenç S, Özdemirkıran F, Eser A, Toptaş T, Özkocaman V et al. A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience. Turk J Hematol. 2019;36(4):230-37. doi: 10.4274/tjh.galenos.2019.2018.0307. 3. Moulis G, Lapeyre-Mestre M, Adoue D, Sailler D. Épidémiologie et pharmacoépidémiologie du purpura thrombopénique immunologique. Rev Med Interne. 2017;38(7): 444-49. doi: 10.1016/j.revmed.2016.12.016.
4. Khadka S, Kasireddy V, Dhakal PK, Dadiboyina C. Evolving treatment modalities for immune thrombocytopenia in adults. J Community Hosp Intern Med Perspect.2021;11(1): 115-19. doi: 10.1080/20009666.2020.1843237.
5. Neunert C, Noroozi N, Norman G, Buchanan GR, Goy J, Nazi I et al.Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost.2015:13(3);457-64. doi: 10.1111/jth.12813.
6. Woolley P, Newton R, Mc Guckin S, Thomas M, Westwood JP, Scully MA. Immune thrombocytopenia in adults: A single‐centre review of demographics, clinical features and treatment outcomes. European journal of haematology. 2020;105(3):344-51. doi.org/10.1111/ejh.13456.
7. Çekdemir D, Diz Küçükkaya R. Treatment and prognosis of immune thrombocytopenia. Turkiye Klinikleri J Hematol-Special Topics. 2014;7:72–79.
8. Choi PY, Roncolato F, Badoux X, Ramanathan S, Ho S, Chong BH et al., A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4). Blood. 2015;126(4):500-3. doi: 10.1182/blood-2015-03- 631937.
9. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829-35. doi: 10.1182/blood-2017-03- 754119.
10. González-López TJ, Sánchez-González B, Jarque I, Bernat S, FernándezFuertes F, Caparrós I et al. Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia. Eur J Haematol. 2020;104(3):259-70. doi: 10.1111/ejh.13370.
11. Thabet AF, Moeen SM. More about the combination of rituximab, cyclosporine, and dexamethasone in the treatment of chronic ITP. A useful option in an environment with limited resources.Platelets.2020;31(6):784-87. doi: 10.1080/09537104.2019.1678121.
12. Cooper N, Ghanima W. Immune thrombocytopenia. New Engl J Med. 2019;381(10): 945-55. doi: 10.1056/NEJMcp1810479.
13. Neunert CE. Management of newly diagnosed immune thrombocytopenia: can we change outcomes? Blood Adv. 2017;1 (24): 2295–301. doi: 10.1182/bloodadvances.2017009860.
14. Gómez‐Almaguer D, Tarín-Arzaga L, Moreno-Jaime B, Jaime-Pérez JC, CeballosLópez AA, Ruiz-Argüelles, GJ et al. High response rate to low‐dose rituximab plus high‐dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia. Eur J Haematol 2013; 90(6):494-500. doi: 10.1111/ejh.12102.
15. 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(23):3829-66. doi: 10.1182/bloodadvances.2019000966
16. Patel VL, Mahévas 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(25):5989-95. doi: 10.1182/blood2011-11-393975.
17. Zaja F, Vianelli N, Volpetti S, Battista ML, Defina M, Palmieri S. et al., Low‐dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2010;85(4):329-34. doi: 10.1111/j.1600-0609.2010.01486.x.
18. Wang H, Tuncer H. A Case of Primary Refractory Immune Thrombocytopenia: Challenges in Choice of Therapies. Case Rep Hematol. 2018;2018:8207017.doi: 10.1155/2018/8207017.
19. Depré F, Aboud N, Mayer B, Salama A. Bidirectional inefficacy or intolerability of thrombopoietin receptor agonists: new data and a concise review. Blood Transfus. 2018;16(3):307. doi: 10.2450/2017.0258-16.

ISSN: 1309-3878
Yayın Aralığı: Yılda 3 Sayı
Başlangıç: 2009
Yayıncı: Düzce Üniversitesi Tıp Fakültesi Aile Hekimliği AD adına Yrd.Doç.Dr.Cemil Işık Sönmez