Cancer Research Journal

| Peer-Reviewed |

Efficacy of Voriconazole Prophylaxis in Pediatric Patients with Acute Myeloid Leukemia, Single Center Experience, Egypt

Received: 02 May 2019    Accepted: 11 June 2019    Published: 24 June 2019
Views:       Downloads:

Share This Article

Abstract

Patients with hematologic malignancies are at higher risk for invasive fungal infections (IFI) mainly patients with acute myeloid leukemia. Antifungal prophylaxis can help to decrease the incidence of these infections and their related complications. Prospective study compared to historical control data included 136 newly diagnosed Acute Myeloid Leukemia patients treated at the National Cancer Institute, Cairo University from 2011 to 2014. The prospective group received primary Voriconazole compared to retrospective control regarding the infectious complications and incidence of fungal infection. Results showed that one hundred thirty-six (136) newly diagnosed pediatric AML patients were included in the study, 61 patients didn't receive antifungal prophylaxis (Non- prophylactic arm) while 75 patients received voriconazole prophylaxis (prophylactic arm). The median age among both groups was 5.5 years old. Thirty-one (50%) of the 61 patients in (non - prophylactic arm) and five (6.6%) of the 75 patients enrolled in group B (prophylactic arm) developed an invasive fungal infection. The most commonly affected sites were pulmonary (34/ 36) while fungal sinus infection was reported in 2 patients. Most patients develop an invasive fungal infection during the induction treatment phase. Primary prophylaxis with voriconazole had a highly statistically significant impact on the reduction of incidence of invasive fungal infection between 2 groups (p value.001). Fungal attributable mortality was reported in 8 patients (13%) in the historical group (no antifungal prophylaxis) in comparison to 2 patients (2.6%) in group patients received voriconazole antifungal prophylaxis. Three Overall and Event-free survival were comparable between both groups. In conclusion, Prophylactic Voriconazole significantly decreased the incidence of fungal infections but it had no impact on diseases or overall survival outcome. Bacterial sepsis and disease-related mortality was the main cause of deaths among our group patients.

DOI 10.11648/j.crj.20190702.15
Published in Cancer Research Journal (Volume 7, Issue 2, June 2019)
Page(s) 58-65
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Acute Myeloid Leukemia, Invasive Fungal Infection, Voriconazole

References
[1] Caira M, Girmenia C, Fadda RM, Mitra ME, Picardi M, Van Lint MT, et al. Invasive fungal infections in patients with acute myeloid leukemia and in those submitted to allogeneic hemopoietic stem cell transplant: who is at highest risk? Eur J Haematol 2008. doi:10.1111/j.1600-0609.2008.01096. x.
[2] Rosen GP, Nielsen K, Glenn S, Abelson J, Deville J, Moore TB. Invasive fungal infections in pediatric oncology patients: 11-Year experience at a single institution. J Pediatr Hematol Oncol 2005. doi:10.1097/01.mph.0000155861.38641.ca.
[3] Steinbach WJ, Walsh TJ. Mycoses in Pediatric Patients. Infect Dis Clin North Am 2006; 20: 663–78. doi:10.1016/j.idc.2006.06.006.
[4] Pana ZD, Vikelouda K, Roilides E. Diagnosis of invasive fungal diseases in pediatric patients. Expert Rev Anti Infect Ther 2016; 14:1203–13. doi:10.1080/14787210.2016.1242413.
[5] L. P, M. C, A. C, M. O, B. M, G. S, et al. Invasive aspergillosis in patients with acute myeloid leukemia: A SEIFEM-2008 registry study. Haematologica 2010.
[6] Pagano L, Caira M. The role of primary antifungal prophylaxis in patients with haematological malignancies. Clin Microbiol Infect 2014. doi:10.1111/1469-0691.12464.
[7] Marks DI, Pagliuca A, Kibbler CC, Glasmacher A, Heussel CP, Kantecki M, et al. Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation. Br J Haematol 2011. doi:10.1111/j.1365-2141.2011.08838. x.
[8] Voriconazole versus Amphotericin B for Invasive Aspergillosis. N Engl J Med 2002. doi:10.1056/nejm200212193472518.
[9] B. J. K, J. D. S, M. R, P. G. P, C. V, J. H. R, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: A randomised non-inferiority trial. Lancet 2005. doi:10.1016/S0140-6736 (05) 67490-9.
[10] De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) C. Clin Infect Dis 2008; 46: 1813–21. doi:10.1086/588660.
[11] Pechlivanoglou P, Le HH, Daenen S, Snowden JA, Postma MJ. Mixed treatment comparison of prophylaxis against invasive fungal infections in neutropenic patients receiving therapy for haematological malignancies: A systematic review. J Antimicrob Chemother 2014. doi:10.1093/jac/dkt329.
[12] Leventakos K, Lewis RE, Kontoyiannis DP. Fungal Infections in Leukemia Patients: How Do We Prevent and Treat Them? Clin Infect Dis 2010. doi:10.1086/649879.
[13] Tacke D, Buchheidt D, Karthaus M, Krause SW, Maschmeyer G, Neumann S, et al. Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 Update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Ann Hematol 2014. doi:10.1007/s00277-014-2108-y.
[14] Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, et al. Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant‐Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010. doi:10.1086/651263.
[15] Even C, Bastuji-Garin S, Hicheri Y, Pautas C, Botterel F, Maury S, et al. Impact of invasive fungal disease on the chemotherapy schedule and event-free survival in acute leukemia patients who survived fungal disease: A case-control study. Haematologica 2011. doi:10.3324/haematol.2010.030825.
[16] Lewis RE, Cahyame-Zuniga L, Leventakos K, Chamilos G, Ben-Ami R, Tamboli P, et al. Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: A 20-year autopsy study. Mycoses 2013. doi:10.1111/myc.12081.
[17] Ethier MC, Science M, Beyene J, Briel M, Lehrnbecher T, Sung L. Mould-active compared with fluconazole prophylaxis to prevent invasive fungal diseases in cancer patients receiving chemotherapy or haematopoietic stem-cell transplantation: A systematic review and meta-analysis of randomised controlled trials. Br J Cancer 2012. doi:10.1038/bjc.2012.147.
[18] Robenshtok E, Gafter-Gvili A, Goldberg E, Weinberger M, Yeshurun M, Leibovici L, et al. Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: Systematic review and meta-analysis. J Clin Oncol 2007. doi:10.1200/JCO.2007.12.3851.
[19] Maron GM, Hayden RT, Rodriguez A, Rubnitz JE, Flynn PM, Shenep JL, et al. Voriconazole prophylaxis in children with cancer: Changing outcomes and epidemiology of fungal infections. Pediatr Infect Dis J 2013. doi:10.1097/INF.0b013e3182a74233.
[20] Alison G. Freifeld, Eric J. Bow, Kent A. Sepkowitz, Michael J. Boeckh, James I. Ito, Craig A. Mullen, Issam I. Raad, Kenneth V. Rolston, Jo-Anne H. Young and JRW. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis 2011. doi:10.1097/IPC.0b013e31822c8f36.
[21] Creutzig U, Zimmermann M, Reinhardt D, Dworzak M, Stary J, Lehrnbecher T. Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: Analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98. J Clin Oncol 2004. doi:10.1200/JCO.2004.01.191.
[22] Imhof A, Balajee SA, Fredricks DN, Englund JA, Marr KA. Breakthrough Fungal Infections in Stem Cell Transplant Recipients Receiving Voriconazole. Clin Infect Dis 2004. doi:10.1086/423274.
[23] Trifilio S, Singhal S, Williams S, Frankfurt O, Gordon L, Evens A, et al. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole. Bone Marrow Transplant 2007. doi:10.1038/sj.bmt.1705754.
[24] Y. M, R. K, H. A-M, N. A, H. T, I. Z, et al. “mucormycosis” the emerging global threat; Overview and treatment outcome among pediatric cancer patients in Egypt. Blood 2017.
[25] 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. doi:10.1086/590566.
Author Information
  • Pediatric Oncology Department, National Cancer Institute, Cairo University, Children Cancer Hospital, Cairo, Egypt

  • Pediatric Oncology Department, National Cancer Institute, Cairo University, Children Cancer Hospital, Cairo, Egypt

  • Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt

  • Pediatric Oncology Department, National Cancer Institute, Cairo University, Children Cancer Hospital, Cairo, Egypt

Cite This Article
  • APA Style

    Youssef Madney, Omar Arafah, Hader Elmahalawy, Lobna Shalby. (2019). Efficacy of Voriconazole Prophylaxis in Pediatric Patients with Acute Myeloid Leukemia, Single Center Experience, Egypt. Cancer Research Journal, 7(2), 58-65. https://doi.org/10.11648/j.crj.20190702.15

    Copy | Download

    ACS Style

    Youssef Madney; Omar Arafah; Hader Elmahalawy; Lobna Shalby. Efficacy of Voriconazole Prophylaxis in Pediatric Patients with Acute Myeloid Leukemia, Single Center Experience, Egypt. Cancer Res. J. 2019, 7(2), 58-65. doi: 10.11648/j.crj.20190702.15

    Copy | Download

    AMA Style

    Youssef Madney, Omar Arafah, Hader Elmahalawy, Lobna Shalby. Efficacy of Voriconazole Prophylaxis in Pediatric Patients with Acute Myeloid Leukemia, Single Center Experience, Egypt. Cancer Res J. 2019;7(2):58-65. doi: 10.11648/j.crj.20190702.15

    Copy | Download

  • @article{10.11648/j.crj.20190702.15,
      author = {Youssef Madney and Omar Arafah and Hader Elmahalawy and Lobna Shalby},
      title = {Efficacy of Voriconazole Prophylaxis in Pediatric Patients with Acute Myeloid Leukemia, Single Center Experience, Egypt},
      journal = {Cancer Research Journal},
      volume = {7},
      number = {2},
      pages = {58-65},
      doi = {10.11648/j.crj.20190702.15},
      url = {https://doi.org/10.11648/j.crj.20190702.15},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.crj.20190702.15},
      abstract = {Patients with hematologic malignancies are at higher risk for invasive fungal infections (IFI) mainly patients with acute myeloid leukemia. Antifungal prophylaxis can help to decrease the incidence of these infections and their related complications. Prospective study compared to historical control data included 136 newly diagnosed Acute Myeloid Leukemia patients treated at the National Cancer Institute, Cairo University from 2011 to 2014. The prospective group received primary Voriconazole compared to retrospective control regarding the infectious complications and incidence of fungal infection. Results showed that one hundred thirty-six (136) newly diagnosed pediatric AML patients were included in the study, 61 patients didn't receive antifungal prophylaxis (Non- prophylactic arm) while 75 patients received voriconazole prophylaxis (prophylactic arm). The median age among both groups was 5.5 years old. Thirty-one (50%) of the 61 patients in (non - prophylactic arm) and five (6.6%) of the 75 patients enrolled in group B (prophylactic arm) developed an invasive fungal infection. The most commonly affected sites were pulmonary (34/ 36) while fungal sinus infection was reported in 2 patients. Most patients develop an invasive fungal infection during the induction treatment phase. Primary prophylaxis with voriconazole had a highly statistically significant impact on the reduction of incidence of invasive fungal infection between 2 groups (p value.001). Fungal attributable mortality was reported in 8 patients (13%) in the historical group (no antifungal prophylaxis) in comparison to 2 patients (2.6%) in group patients received voriconazole antifungal prophylaxis. Three Overall and Event-free survival were comparable between both groups. In conclusion, Prophylactic Voriconazole significantly decreased the incidence of fungal infections but it had no impact on diseases or overall survival outcome. Bacterial sepsis and disease-related mortality was the main cause of deaths among our group patients.},
     year = {2019}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Efficacy of Voriconazole Prophylaxis in Pediatric Patients with Acute Myeloid Leukemia, Single Center Experience, Egypt
    AU  - Youssef Madney
    AU  - Omar Arafah
    AU  - Hader Elmahalawy
    AU  - Lobna Shalby
    Y1  - 2019/06/24
    PY  - 2019
    N1  - https://doi.org/10.11648/j.crj.20190702.15
    DO  - 10.11648/j.crj.20190702.15
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 58
    EP  - 65
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20190702.15
    AB  - Patients with hematologic malignancies are at higher risk for invasive fungal infections (IFI) mainly patients with acute myeloid leukemia. Antifungal prophylaxis can help to decrease the incidence of these infections and their related complications. Prospective study compared to historical control data included 136 newly diagnosed Acute Myeloid Leukemia patients treated at the National Cancer Institute, Cairo University from 2011 to 2014. The prospective group received primary Voriconazole compared to retrospective control regarding the infectious complications and incidence of fungal infection. Results showed that one hundred thirty-six (136) newly diagnosed pediatric AML patients were included in the study, 61 patients didn't receive antifungal prophylaxis (Non- prophylactic arm) while 75 patients received voriconazole prophylaxis (prophylactic arm). The median age among both groups was 5.5 years old. Thirty-one (50%) of the 61 patients in (non - prophylactic arm) and five (6.6%) of the 75 patients enrolled in group B (prophylactic arm) developed an invasive fungal infection. The most commonly affected sites were pulmonary (34/ 36) while fungal sinus infection was reported in 2 patients. Most patients develop an invasive fungal infection during the induction treatment phase. Primary prophylaxis with voriconazole had a highly statistically significant impact on the reduction of incidence of invasive fungal infection between 2 groups (p value.001). Fungal attributable mortality was reported in 8 patients (13%) in the historical group (no antifungal prophylaxis) in comparison to 2 patients (2.6%) in group patients received voriconazole antifungal prophylaxis. Three Overall and Event-free survival were comparable between both groups. In conclusion, Prophylactic Voriconazole significantly decreased the incidence of fungal infections but it had no impact on diseases or overall survival outcome. Bacterial sepsis and disease-related mortality was the main cause of deaths among our group patients.
    VL  - 7
    IS  - 2
    ER  - 

    Copy | Download

  • Sections