Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study
Yıl: 2023 Cilt: 13 Sayı: 1 Sayfa Aralığı: 9 - 15 Metin Dili: İngilizce DOI: 10.4274/buchd.galenos.2022.92489 İndeks Tarihi: 24-05-2023
Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study
Öz: Objective: The role of combination regimens in the treatment of invasive fungal infections (IFIs) in hematologic malignancies remains unclear. We aimed to demonstrate data about combined antifungal therapy (CAT) in pediatric leukemia patients with IFI. Method: Between January 2014 and December 2018, a total of 33 IFI episodes in 28 leukemia patients were analyzed retrospectively. Results: The study patients had acute lymphoblastic leukemia (n=19), acute myeloblastic leukemia (n=9), leukemia relapse (n=21; 75%) and remission (n=7; 25%). The patients were classified as having possible (n=26; 78.8%), probable (n=5; 15.1%) and proven IFI (n=2; 6.1%). Liposomal amphotericin B (LamB) was the most preferred agent (50%) in monotherapy. Mean duration of monotherapy was 12.84±4.28 (5-24) days. LamB plus voriconazole (54.5%) was the most commonly preferred CAT. Mean duration of CAT was 42.36±36.4 days, and this combination regimen was not changed throughout the treatment period (p=0.571). Total and IFI-related mortality rates were 60.7% vs 46.4%, respectively. Mortality rates were significantly higher in patients with relapse (p=0.006). Complete response was obtained in 81.8% of surviving patients. Side effects of CAT were observed at quite a low level. Conclusion: CAT has been found to be safe in the treatment of IFI episodes of pediatric leukemia. Uncontrolled underlying disease is the most important factor affecting the mortality rates in IFI.
Anahtar Kelime: Pediatrik Lösemi Hastalarında İnvaziv Mantar Enfeksiyonları için Antifungal Kombinasyon Tedavisi: Gözlemsel Bir Kohort Çalışması
Öz: Amaç: Hematolojik malignitelerde invaziv fungal enfeksiyonların (İFE) tedavisinde kombinasyon rejimlerinin rolü belirsizliğini korumaktadır. Bu çalışmada, lösemili pediyatrik İFE hastalarında kombine antifungal tedavi (KAT) ile ilgili verilerin sunulması amaçlamıştır. Yöntem: Ocak 2014 ile Aralık 2018 arasında, lösemili 28 hastada toplam 33 İFE atağı geriye dönük olarak analiz edildi. Bulgular: Hastaların (19’u akut lenfoblastik lösemili ve 9’u akut miyeloblastik lösemili), 21’inde (%75) lösemi relapsı ve 7’sinde (%25) remisyon mevcuttu. İFE, 26 (%78,8) atakta mümkün, 5 (%15,1) atakta olası ve 2 (%6,1) atakta kanıtlı idi. Monoterapide en çok tercih edilen ajan (%50) lipozomal amfoterisin B (LamB) idi. Ortalama monoterapi süresi 12,84±4,28 (5-24) gündü. KAT’da en sık kombinasyon tercihi LamB artı vorikonazol (%54,5) idi. Ortalama KAT süresi 42,36±36,4 gündü ve kombinasyon rejimi tipine göre değişmiyor idi (p=0,571). Toplam mortalite oranı ve İFE’ye atfedilebilir ölüm oranı %60,7’ye karşılık %46,4 idi. Relaps olan hastalarda mortalite oranı anlamlı olarak daha yüksekti (p=0,006). Hayatta kalan hastaların %81,8’inde tam yanıt alındı. KAT kullanımına bağlı yan etkiler oldukça düşük düzeyde gözlendi. Sonuç: Pediyatrik löseminin İFE ataklarında KAT güvenli bulunmuştur. İFE’de mortalite oranını etkileyen en önemli faktör kontrolsüz altta yatan hastalıktır.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Cesaro S, Tridello G, Castagnola E, Calore E, Carraro F, Mariotti I, et al. Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high-risk pediatric onco-hematological patients. Eur J Haematol. 2017;99(3):240-8. doi:10.1111/ejh.12910
- 2. Kobayashi R, Hori D, Sano H, Suzuki D, Kishimoto K, Kobayashi K. Risk Factors for Invasive Fungal Infection in Children and Adolescents With Hematologic and Malignant Diseases: A 10- year Analysis in a Single Institute in Japan. Pediatr Infect Dis J. 2018;37(12):1282-5. doi:10.1097/INF.0000000000002010
- 3. Puia-Dumitrescu M, Smith PB. Antifungal Drugs in Newborns and Children. Pediatr Clin North Am. 2017;64(6):1389-402. doi:10.1016/j.pcl.2017.08.013
- 4. Ramos-Martín V, O’Connor O, Hope W. Clinical pharmacology of antifungal agents in pediatrics: children are not small adults. Curr Opin Pharmacol. 2015;24:128-34. doi:10.1016/j.coph.2015.08.009
- 5. Pagano L, Caira M, Valentini CG, Posteraro B, Fianchi L. Current therapeutic approaches to fungal infections in immunocompromised hematological patients. Blood Rev. 2010;24(2):51-61. doi:10.1016/j.blre.2009.11.003
- 6. Candoni A, Caira M, Cesaro S, Busca A, Giacchino M, Fanci R, et al. Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study. Mycoses. 2014;57(6):342-50. doi:10.1111/ myc.12161
- 7. Day JN, Chau TT, Lalloo DG. Combination antifungal therapy for cryptococcal meningitis. N Engl J Med. 2013;368:2522-3. doi:10.1056/NEJMc1305981
- 8. Mihu CN, Kassis C, Ramos ER, Jiang Y, Hachem RY, Raad II. Does combination of lipid formulation of amphotericin B and echinocandins improve outcome of invasive aspergillosis in hematological malignancy patients? Cancer. 2010;116(22):5290-6.
- 9. MacCallum DM, Whyte JA, Odds FC. Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis. Antimicrob Agents Chemother. 2005;49(9):3697-701. doi:10.1128/ AAC.49.9.3697-3701.2005
- 10. Ibrahim AS, Gebremariam T, Fu Y, Edwards JE Jr, Spellberg B. Combination echinocandin-polyene treatment of murine mucormycosis. Antimicrob Agents Chemother. 2008;52:1556-8. doi:10.1128/AAC.01458-07
- 11. Kirkpatrick WR, Coco BJ, Patterson TF. Sequential or combination antifungal therapy with voriconazole and liposomal amphotericin B in a guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother. 2006;50(4):1567-9. doi:10.1128/ AAC.50.4.1567-1569.2006
- 12. Cesaro S, Giacchino M, Locatelli F, Spiller M, Buldini B, Castellini C, et al. Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients. BMC Infect Dis. 2007;7:28. doi:10.1186/1471-2334-7-28
- 13. Raad II, Zakhem AE, Helou GE, Jiang Y, Kontoyiannis DP, Hachem R. Clinical experience of the use of voriconazole, caspofungin or the combination in primary and salvage therapy of invasive aspergillosis in haematological malignancies. Int J Antimicrob Agents. 2015;45(3):283-8. doi:10.1016/j.ijantimicag.2014.08.012
- 14. Wattier RL, Dvorak CC, Hoffman JA, Brozovich AA, Bin-Hussain I, Groll AH, et al. A Prospective, International Cohort Study of Invasive Mold Infections in Children. J Pediatric Infect Dis Soc. 2015;4(4):313-22. doi:10.1093/jpids/piu074
- 15. Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Inern Med. 2015;162(2):81-9. doi:10.7326/M13-2508
- 16. Lignieres G, Guitard J, Alby-Laurent F, Rambaud J, Bigot J, Morand K, et al. Antifungal combination therapy for invasive fungal infections in a paediatric oncology and haematology department: A retrospective analysis of practice. J Mycol Med. 2022;32(3):101276. doi:10.1016/j.mycmed.2022.101276
- 17. Schöning S, Bochennek K, Gordon K, Groll AH, Lehrnbecher T. Antifungal Combination Therapy in Children with Cancer-A 4-Year Analysis of Real-Life Data of Two Major Pediatric Cancer Centers. J Fungi (Basel). 2021;7(8):604. doi:10.3390/jof7080604
- 18. Kazakou N, Vyzantiadis TA, Gambeta A, Vasileiou E, Tsotridou E, Kotsos D, et al. Invasive fungal infections in a pediatric hematology-oncology department: A 16-year retrospective study. Curr Med Mycol. 2020;6(2):37-42. doi:10.18502/CMM.6.2.2840
- 19. Meena JP, Gupta AK, Jana M, Seth R. Combination antifungals as an effective means of salvage in paediatric leukaemia patients with invasive fungal infections. Indian J Med Microbiol. Indian J Med Microbio. 2019;37(1):109-12. doi:10.4103/ijmm.IJMM_18_157
- 20. Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008;47(5):674-83. doi:10.1086/590566
- 21. Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15(8):327-40. doi:10.1016/S1470-2045(14)70017-8
- 22. Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):1-60. doi: 10.1093/cid/ciw326
- 23. Lee KH, Lim YT, Hah JO, Kim YK, Lee CH, Lee JM. Voriconazole plus caspofungin for treatment of invasive fungal infection in children with acute leukemia. Blood Res. 2017;52(3):167-173. doi:10.5045/ br.2017.52.3.167
- 24. Kurosawa M, Yonezumi M, Hashino S, Tanaka J, Nishio M, Kaneda M, et al. Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol. 2012;96(96):748-57. doi:10.1007/s12185-012-1210-y
- 25. Georgiadou SP, Pongas G, Fitzgerald NE, Lewis RE, Rytting M, Marom EM, et al. Invasive Mold Infections in Pediatric Cancer Patients Reflect Heterogeneity in Etiology, Presentation, and Outcome: A 10-Year, Single-Institution, Retrospective Study. J Pediatric Infect Dis Soc. 2012;1(2):125-35. doi:10.1093/jpids/pis042
- 26. Çağlar İ, Devrim İ, Özdemir H, Şahbudak Z, Sönmez G, Buyukcam A, et al. Antifungal consumption, indications and selection of antifungal drugs in paediatric tertiary hospitals in Turkey: Results from the first national point prevalence survey. J Glob Antimicrob Resist. 2018;15:232-8. doi:10.1016/j.jgar.2018.08.007
- 27. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother. 2002;46:3039-41. doi:10.1128/ AAC.46.9.3039-3041.2002
- 28. Petraitis V, Petraitiene R, Sarafandi AA, Kelaher AM, Lyman CA, Casler HE, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin. J Infect Dis. 2003;187:1834-43. doi: 10.1086/375420
- 29. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39(6):797-802. doi:10.1086/423380
- 30. Groll AH, Silling G, Young C, Schwerdtfeger R, Ostermann H, Heinz WJ, et al. Randomized comparison of safety and pharmacokinetics of caspofungin, liposomal amphotericin B, and the combination of both in allogeneic hematopoietic stem cell recipients. Antimicrob Agents Chemother. 2010;54(10):4143-9. doi: 10.1128/AAC.00425-10
| APA | kanik yuksek s, Ozkaya Parlakay A, gülhan b, YARALI N, ozbek n, TEZER H (2023). Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. , 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| Chicago | kanik yuksek saliha,Ozkaya Parlakay Aslinur,gülhan belgin,YARALI NESE,ozbek namik yasar,TEZER HASAN Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. (2023): 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| MLA | kanik yuksek saliha,Ozkaya Parlakay Aslinur,gülhan belgin,YARALI NESE,ozbek namik yasar,TEZER HASAN Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. , 2023, ss.9 - 15. 10.4274/buchd.galenos.2022.92489 |
| AMA | kanik yuksek s,Ozkaya Parlakay A,gülhan b,YARALI N,ozbek n,TEZER H Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. . 2023; 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| Vancouver | kanik yuksek s,Ozkaya Parlakay A,gülhan b,YARALI N,ozbek n,TEZER H Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. . 2023; 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| IEEE | kanik yuksek s,Ozkaya Parlakay A,gülhan b,YARALI N,ozbek n,TEZER H "Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study." , ss.9 - 15, 2023. 10.4274/buchd.galenos.2022.92489 |
| ISNAD | kanik yuksek, saliha vd. "Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study". (2023), 9-15. https://doi.org/10.4274/buchd.galenos.2022.92489 |
| APA | kanik yuksek s, Ozkaya Parlakay A, gülhan b, YARALI N, ozbek n, TEZER H (2023). Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. Journal of Behçet Uz children's hospital (Online), 13(1), 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| Chicago | kanik yuksek saliha,Ozkaya Parlakay Aslinur,gülhan belgin,YARALI NESE,ozbek namik yasar,TEZER HASAN Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. Journal of Behçet Uz children's hospital (Online) 13, no.1 (2023): 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| MLA | kanik yuksek saliha,Ozkaya Parlakay Aslinur,gülhan belgin,YARALI NESE,ozbek namik yasar,TEZER HASAN Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. Journal of Behçet Uz children's hospital (Online), vol.13, no.1, 2023, ss.9 - 15. 10.4274/buchd.galenos.2022.92489 |
| AMA | kanik yuksek s,Ozkaya Parlakay A,gülhan b,YARALI N,ozbek n,TEZER H Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. Journal of Behçet Uz children's hospital (Online). 2023; 13(1): 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| Vancouver | kanik yuksek s,Ozkaya Parlakay A,gülhan b,YARALI N,ozbek n,TEZER H Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study. Journal of Behçet Uz children's hospital (Online). 2023; 13(1): 9 - 15. 10.4274/buchd.galenos.2022.92489 |
| IEEE | kanik yuksek s,Ozkaya Parlakay A,gülhan b,YARALI N,ozbek n,TEZER H "Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study." Journal of Behçet Uz children's hospital (Online), 13, ss.9 - 15, 2023. 10.4274/buchd.galenos.2022.92489 |
| ISNAD | kanik yuksek, saliha vd. "Antifungal Combination Therapy for Invasive Fungal Infections in Pediatric Leukemia Patients: An Observational Cohort Study". Journal of Behçet Uz children's hospital (Online) 13/1 (2023), 9-15. https://doi.org/10.4274/buchd.galenos.2022.92489 |
