Akut Lenfoblastik Lösemili Hastalarda Mikafungin Profilaksisi

Yıl 2022, Sayı: 16, 1 - 12, 30.04.2022

Burak Deveci , Orhan Kemal Yücel , George Kublashvili , Utku Iltar , Ünal Ataş , Tayfur Toptas , Özge Turhan , Rabin Saba

https://doi.org/10.38079/igusabder.993158

Öz

Amaç: Hematolojik maligniteli hastaların tedavisindeki gelişmelere rağmen invaziv fungal infeksiyon (İFİ), bu hastalıkların seyri sırasında önemli bir morbidite ve mortalite nedeni olmaya devam etmektedir. Antilösemik tedavinin başarısı ve komplikasyon gelişme riskini azaltabilmesi nedeniyle antifungal profilaksi önem arz etmektedir.

Yöntem: Bu retrospektif çalışmada profilaktik bir antifungal olarak mikafunginin akut lenfoblastik lösemi (ALL) hastalarındaki etkinliği ve güvenilirliliği değerlendirilmiştir. Çalışmaya erişkin yaş grubundaki ALL tanısı ile indüksiyon, reindüksiyon veya kurtarma tedavisi alan ve tedavi sırasında mikafungin ile antifungal profilaksi uygulanan 36 hasta ve bu hastaların almış oldukları toplam 113 kemoterapi kürü dahil edilmiştir. Hastaların tamamına indüksiyon, reindüksiyon ve konsolidasyon tedavileri sırasında mikafungin 50 mg/gün intravenöz profilaksisi verilmiştir. Çalışmanın sonlanım noktası olarak ise; tedavinin tamamlanması, profilaksi altında ampirik, preemptif veya hedefe yönelik antifungal değişikliği ve herhangi bir nedenle ölüm kabul edilmiştir.

Bulgular: Çalışmamızın sonuçları incelendiğinde ALL hastalarında İFİ varlığı ile sağ kalım arasındaki kuvvetli ilişki ilk başta dikkati çekmektedir. Bununla birlikte; yan etki veya ilaç etkileşimi nedeniyle tedaviyi kesme gerekliliğinin olmaması, düşük preemptif antifungal ihtiyacı, ALL hastalarında mikafungin profilaksisinin etkinliğini göstermiştir.

Sonuç: Etkin ve güvenilir bir antifungal profilaksi stratejisi bu grup hastalar için hayati önem taşımaktadır, hayat kurtarıcı olabilmektedir.

Anahtar Kelimeler

Lösemi, İnvazif fungal enfeksiyon, Mortalite

Teşekkür

Bize hem mesleğimizde hem bu çalışmamızda büyük katkı sağlayan ancak aramızdan ayrılan rahmetli hocamız Prof. Dr. İhsan Karadoğan 'a sonsuz teşekkür ederiz.

Micafungin Prophylaxis in Patients with Acute Lymphoblastic Leukemia

Öz

Aim: Despite advances in the treatment of patients with hematological malignancies, invasive fungal infection (IFI) remains an important cause of morbidity and mortality during the course of these diseases. Antifungal prophylaxis is important because of the success of antileukemic treatment and reducing the risk of complications.

Methods: This retrospective study evaluated the efficacy and safety of micafungin as a prophylactic antifungal in patients with acute lymphoblastic leukemia (ALL). A total of 113 chemotherapy courses were included in the study, which included 36 patients with the diagnosis of ALL in the adult age group who received induction, reinduction or salvage therapy, and received antifungal prophylaxis with micafungin during the treatment. Micafungin 50 mg/day intravenous prophylaxis was given to all patients during induction, induction and consolidation treatments. The endpoint of the study was accepted as; treatment completion, empirical, preemptive or targeted antifungal change under prophylaxis, and death from any cause.

Results: When the results of our study are examined, the strong relationship between the presence of IFI and survival in ALL patients is remarkable at first. On the other hand; the absence of the need to discontinue treatment due to side effects or drug interactions, and the low need for preemptive antifungals have demonstrated the efficacy of micafungin prophylaxis in ALL patients.

Conclusion: An effective and reliable antifungal prophylaxis strategy is vital for this group of patients and can be life-saving.

Anahtar Kelimeler

Leukemia, Mortality, Invasive fungal infection

Kaynakça

• Martino R, Subira M. Invasive fungal infections in hematology: new trends. Ann Hematol. 2002;81:233–43.
• Pagano L, Caira M, Candoni A, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.
• Böhme A, Ruhnke M, Buchheidt D, et al. Treatment of invasive fungal infections in cancer patients. Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2009;88:97–110.
• Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34:909–17.
• Mühlemann K, Wenger C, Zenhäusern R, et al. Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies. Leukemia. 2005;19:545–50.
• Cuenca-Estrella M, Bernal-Martinez L, Buitrago MJ, et al. Update on the epidemiology and diagnosis of invasive fungal infection. Int J Antimicrob Agents. 2008;32 (Suppl 2): S143–7.
• Brakhage AA. Systemic fungal infections caused by Aspergillus species: epidemiology, infection process and virulence determinants. Curr Drug Targets. 2005;6:875–86.
• Othus M, Kantarjian H, Petersdorf S, et al. Declining rates of treatment-related mortality in patients with newly diagnosed AML given 'intense' induction regimens: a report from SWOG and MD Anderson. Leukemia. 2014;28(2):289–92.
• Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356(4):348–59.
• Hammond SP, Marty FM, Bryar JM, DeAngelo DJ, Baden LR. Invasive fungal disease in patients treated for newly diagnosed acute leukemia. Am J Hematol. 2010;85(9):695–9.
• Gründahl M, Wacker B, Einsele H, Heinz WJ. Invasive fungal diseases in patients with new diagnosed acute lymphoblastic leukaemia. Mycoses. 2020;63(10):1101-1106. doi:10.1111/myc.13151.
• Enoch DA, Idris SF, Aliyu SH, Micallef C, Sule O, Karas JA. Mikafungin for the treatment of invasive aspergillosis. J Infect. 2014;68(6):507-26. doi:10.1016/j.jinf.2014.01.007.
• Wasmann RE, Muilwijk EW, Burger DM, Verweij PE, Knibbe CA, Brüggemann RJ. Clinical Pharmacokinetics and Pharmacodynamics of Mikafungin. Clin Pharmacokinet. 2018;57(3):267-286. doi:10.1007/s40262-017-0578-5.
• Morris H, Moorman MT, Mackey MC, et al. Incidence of invasive fungal infections in acute leukemia patients utilizing Mikafungin Prophylaxis compared to second-generation Azole Prophylaxis. Blood. 2019; 134:5105. doi: http://doi.org/10.1182/blood-2019-132197.
• El Cheikh J, Venton G, Crocchiolo R, et al. Efficacy and safety of mikafungin for prophylaxis of invasive fungal infections in patients undergoing haplo identical hematopoietic SCT. Bone Marrow Transplant. 2013;4811:1472-1477. doi:10.1038/bmt.2013.87.
• Ullmann AJ, Sanz MA, Tramarin A, et al. Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries. Clin Infect Dis. 2006;43:e29–38.
• Walsh TJ, Teppler H, Donowitz GR, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351:1391–402.
• Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.
• Park H, Youk J, Shin DY, et al. Mikafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy. BMC Cancer. 2019;16:19(1):358. doi:10.1186/s12885-019-5557-9.
• Hahn-Ast C, Glasmacher A, Mückter S, et al. Overall survival and fungal infection-related mortality in patients with invasive fungal infection and neutropenia after myelosuppressive chemotherapy in a tertiary care centre from 1995 to 2006. J Antimicrob Chemother. 2010;65(4):761–768. doi:10.1093/jac/dkp507.
• Zeng H, Wu Z, Yu B, et al. Network meta-analysis of triazole, polyene, and echinocandin antifungal agents in invasive fungal infection prophylaxis in patients with hematological malignancies. BMC Cancer. 2021;14:21(1):404. doi:10.1186/s12885-021-07973-8.