Yüksek Riskli Hematolojik Hastalarda Profilaktik Posakanazol Kullanımının Fungal Enfeksiyon Gelişimi Üzerine Etkisi: Türkiye'de Tek Merkez Deneyimi

Giriş: İnvaziv fungal enfeksiyonlar (IFI), remisyon-indüksiyon tedavisi alan ve allojenik kök hücre nakli yapılan akut myeloid lösemi ve myelodisplastik sendromlu hastalarda en önemli morbidite ve mortalite nedenidir. Tanı koymadaki güçlükler ve tanı koymadaki gecikmeler mortaliteyi artırmaktadır. Bu komplikasyonları azaltmak için birçok klinisyen ve uluslararası kılavuzlar tarafından antifungal profilaksi yapılması önerilmektedir. Posakanazol, yeni jenerasyon, geniş spektrumlu oral azol olup yapılan 2 randomize çalışma ile IFI gelişme riskini ve mortaliteyi de azalttığı gösterilmiştir. Bu çalışmada, posakonazol proflaksisinin, remisyon-indüksiyon tedavisi ( antrasiklin bazlı tedaviler ) alan akut myeloid lösemi ve myelodisplastik sendromlu ve allojenik kök hücre nakli yapılan hastalarda invaziv mantar enfeksiyonu önlemede etkinlik, güvenlilik ve tolere edilebilirliğinin değerlendirilmesi amaçlandı. Yöntemler: Retrospektif çalışmaya 2007-2020 yılları arasında takip edilen 117 hasta çalışmaya alındı. Hastalar posakanazol ve kontrol grubu olarak iki gruba ayrıldı. Posakanazol grubuna remisyon-indüksiyon tedavisi alan 39 AML ve allojenik kök hücre nakli yapılan 10 AML-MDS hasta alındı, gruptaki tüm hastalar posakanazol ile tedavi edildi. Kontrol grubuna ise remisyon-indüksiyon tedavisi esnasında profilaksi almayan 58 AML tanılı hasta ve flukanazol profilaksi alan 10 AML-MDS hasta alındı. Posakanazol kullanan ve kontrol grubundaki hastalarda fungal enfeksiyon tanısında ve şüphesinde EORTC/MSG (Avrupa Kanser Araştırma ve Tedavi Organizasyonu/ (Mikoz Çalışma Grubu) tanı kriterleri kullanıldı. Tanıya yönelik HRCT (Yüksek Rezolusyonlu Akciğer Tomografisi) gibi görüntüleme tekniklerinin yanı sıra galaktomannan gibi biyokimyasal tetkiklerde incelendi. Bulgular: Bu çalışmada allojenik kök hücre nakli yapılan MDS ve AML hasta grubunda posakanazol profilaksisi kullanılanlarda fungal enfeksiyon gelişme riskinin ve antifungal kullanım ihtiyacının diğer gruba oranla daha düşük olduğu saptandı (P<0,001). Kontrol grubunda (profilakside flukanazol kullanılan hasta grubu) olası veya şüpheli fungal enfeksiyonu gösteren HRCT bulguları daha yüksek oranda tespit edildi (P=0,001). Yaş, cinsiyet gibi sosyodemografik özelliklerinin yanı sıra galaktomannan düzeyi, mikrobiyolojik incelemeler, remisyon durumu ve risk faktörleri açısından her iki grup arasında bir anlamlı farklılık yoktu (P>0,05). Tedavi esnasında yan etki gelişimi açısından iki grup arasında herhangi bir fark yoktu(P>0,05). Sonuç: Bu çalışmada literatür ile uyumlu olarak remisyon-indüksiyon tedavisi alan hastalarda invaziv fungal enfeksiyon gelişimini önlemede profilaktik posakanazol kullanımının etkin ve güvenli olduğu, allojenik kök hücre nakli yapılan hastalarda ise profilaktik posakanazol kullanımının flukanazol kullanımına göre daha üstün olduğu gösterilmiştir

Anahtar Kelimeler:

profilaksi, posakanazol, fungal enefeksiyon, mortalite

The Effect of Posaconazole Prophylaxes on the Course of Fungal Infection in the High Risk Patients of Hematology: A Single-Center Experience in Turkey

Introduction: Invasive fungal infections (IFIs) are the most important cause of morbidity and mortality in the patients treated with remission-induction therapy and allogeneic stem cell transplantation (ASCT) and suffering from acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Difficulties and delays in diagnosis of the disease increase the mortality rate. Many clinicians and qualified international guidelines recommend the use of antifungal prophylaxis to reduce complications of the AML. Posaconazole is a new generation of broad spectrum oral azole and recent studies have shown that it is effective in curtailing risk of developing IFIs and mortality as well. In the present study, we aimed to assess the effectiveness of posaconazole prophylaxis on preventing development of IFIs, its reliability, and its tolerability in the patients treated with remission-induction therapy and ASCT and suffering from AML and MDS. Methods: Overall, 117 patients were enrolled to the present retrospective study covering the patients followed between the years 2007 and 2020. The patients were divided into two groups as posaconazole group and control group. The posaconazole group contained 39 AML patients put on remission induction chemotherapy and 10 AML-MDS patients that received allogeneic stem cell transplantation, and all the patients in the posaconazole group were treated with posaconazole. The control group comprised 58 AML patients receiving no prophylactic antifungal treatment during the remission induction chemotherapy and 10 AML-MDS patients treated with fluconazole. Diagnoses and suspicions of fungal infections in posaconazole group and control groups were verified using the criteria set by EORTC/MSG. In addition, imaging techniques such as high-HRCT and biochemical tests, i.e., galactomannan were also utilized for diagnoses purposes. Results: In the present study, we noted that the risk for the development of fungal infections and the need for antifungal use in the MDS and AML patients who received ASCT were markedly reduced in the patients administered with posaconazole prophylaxis in comparison to other group (P<0.001). The frequency of HRCT (High- Resolution Computed Tomography) findings implying potential or suspected development of fungal infections was determined to be greater in the control group (the patients treated with fluconazole prophylaxis) (P=0.001). In addition, there were no discernible differences between the groups for the socio-demographic characteristics such as age and gender in addition to the level of galactomannan, microbiological analysis, remission status and risk factors (P> 0.05). Finally, no significant difference was noticed on the development of side effects during the treatment between the groups (P> 0.05). Conclusion: The results of the present study were consistent with the literature and indicated that the use of posaconazole for prophylactic purposes was more effective and reliable than fluconazole in preventing development and spread of invasive fungal infections in the patient receiving remission induction chemotherapy and ASCT.

Keywords:

Prophylaxes, Posaconazole, Fungal Infection, mortality,

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