Vol 52, No 5 (2021)
Original research article
Published online: 2021-04-20
High risk of invasive fungal disease in children undergoing hematopoietic cell transplantation or complex anticancer therapy: the adverse role of post-transplant CMV replication
1
, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1
, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1
Acta Haematol Pol 2021;52(5):483-492.
Abstract
Introduction: We analyzed the epidemiology and outcomes of treatment of invasive fungal disease (IFD) in children during anticancer therapy (PHO, pediatric hematology and oncology) or after hematopoietic cell transplantation (HCT) over a period of eight consecutive years in a single-center study.
Material and methods: Overall, a total of 254 HCTs were performed, and 415 children were newly diagnosed for malignancy. Incidence, epidemiology and outcome of IFD were analyzed.
Results: The cumulative incidence of any IFD was 32.6% in allo-HCT, 22.2% in PHO, and 6.0% in auto-HCT patients. The incidence of proven +probable IFD was 12.6%, 10.4%, and 6.0%, respectively. As many as 77.0% HCT and 67.4% PHO of fungal episodes occurred in acute leukemia patients: the highest incidence of any IFD was observed for acute lymphoblastic leukemia (29.3% in HCT; 40.5% in PHO) and for acute myeloblastic leukemia (51.1% in HCT; 65.0% in PHO) patients. There were no significant differences in the incidence of fungal infections in both allo-HCT and PHO patients between the 2-year periods. Factors contributing to an increased risk of IFD in allo-HCT patients were: CMV replication, and acute and chronic graft-versus-host disease (GvHD). Survival from IFD was 91.9% in PHO, and 78.1% in HCT patients. Fungal pneumonia in HCT patients resolved in 62.9%, while in PHO patients it resolved in 93.5%.
Conclusions: The risk of IFD in allo-HCT patients is much higher than in auto-HSCT and PHO patients. The outcome of IFD is better in PHO and auto-HCT than in allo-HCT settings.
Keywords: fungal infectionsmalignant diseasespediatric hematology and oncologyhematopoietic cell transplantationchildren
References
- Kontoyiannis DP, Marr KA, Park BJ, 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; 50(8): 1091–1100.
- Styczyński J. Infectious complications in children and adults with hematological malignancies. Acta Haematologica Polonica. 2019; 50(3): 167–173.
- Maertens J, Marchetti O, Herbrecht R, et al. Third European Conference on Infections in Leukemia. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3-2009 update. Bone Marrow Transplant. 2011; 46(5): 709–718.
- Styczyński J. ABC of viral infections in hematology: focus on herpesviruses. Acta Haematologica Polonica. 2019; 50(3): 159–166.
- Averbuch D, Cordonnier C, Livermore DM, et al. ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011). Haematologica. 2013; 98(12): 1836–1847.
- Averbuch D, Orasch C, Cordonnier C, et al. ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013; 98(12): 1826–1835.
- Ljungman P, de la Camara R, Cordonnier C, et al. European Conference on Infections in Leukemia. Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant. 2008; 42(4): 227–240.
- Styczynski J, Reusser P, Einsele H, et al. Second European Conference on Infections in Leukemia. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009; 43(10): 757–770.
- Groll AH, Castagnola E, Cesaro S, et al. Fourth European Conference on Infections in Leukaemia, Infectious Diseases Working Party of the European Group for Blood Marrow Transplantation (EBMT-IDWP), Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC-IDG), International Immunocompromised Host Society (ICHS), European Leukaemia Net (ELN). 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): e327–e340.
- Styczynski J, Czyzewski K, Wysocki M, et al. Polish Society of Paediatric Oncology and Haematology. Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study. Clin Microbiol Infect. 2016; 22(2): 179.e1–179.e10.
- Salamonowicz M, Ociepa T, Frączkiewicz J, et al. Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation. Eur J Clin Microbiol Infect Dis. 2018; 37(9): 1805–1812.
- Czyzewski K, Galazka P, Zalas-Wiecek P, et al. Infectious complications in children with malignant bone tumors: a multicenter nationwide study. Infect Drug Resist. 2019; 12: 1471–1480.
- Czyżewski K, Styczyński J, Giebel S, et al. for Polish Society of Pediatric Oncology and Hematology and Polish Society of Hematology and Blood Transfusion. Age-dependent determinants of infectious complications profile in children and adults after hematopoietic cell transplantation: lesson from the nationwide study. Ann Hematol. 2019; 98(9): 2197–2211.
- Czyżewski K, Gałązka P, Frączkiewicz J, et al. Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: Impact of national programme of antifungal prophylaxis. Mycoses. 2019; 62(11): 990–998.
- Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020; 71(6): 1367–76.
- De Pauw P, Walsh TJ, Donnelly JP, 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) consensus group. Clin Infect Dis. 2008; 46(12): 1813–1821.
- Gil L, Kałwak K, Piekarska A, et al. Antifungal management in adults and children with hematological malignancies or undergoing hematopoietic cell transplantation: recommendations of Polish Society of Hematology and Blood Transfusion, Polish Society of Pediatric Oncology and Hematology, and Polish Adult Leukemia Study Group, 2020. Acta Haematologica Polonica. 2020; 51(2): 60–72.
- Styczyński J, Czyżewski K, Frączkiewicz J, et al. Clinical spectrum and outcome of invasive mucormycosis in children and adults: Polish experience of the decade 2010–2019. Acta Haematologica Polonica. 2020; 51(3): 157–163.
- Styczynski J, Gil L. EBMT Paediatric Diseases Working Party. Prevention of infectious complications in pediatric HSCT. Bone Marrow Transplant. 2008; 42(Suppl 2): S77–S81.
- Styczyński J, Czyżewski K, Ussowicz M, et al. Antimicrobial prophylaxis in patients after hematopoietic cell transplantation: results of a survey of the Polish Federation of Bone Marrow Transplant Centers. Acta Haematologica Polonica. 2020; 51(3): 183–186.
- Styczynski J, Tridello G, Donnelly JP, et al. Protective environment for hematopoietic cell transplant (HSCT) recipients: The Infectious Diseases Working Party EBMT analysis of global recommendations on health-care facilities. Bone Marrow Transplant. 2018; 53(9): 1131–1138.
- Gałązka P, Dziedzic M, Czyżewski K, et al. Differential risk of viral infections in children undergoing complex anticancer therapy or hematopoietic stem cell transplantation. Med Res J. 2018; 3(3): 127–133.
- Srinivasan A, Wang C, Srivastava DK, et al. Timeline, epidemiology, and risk factors for bacterial, fungal, and viral infections in children and adolescents after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(1): 94–101.
- Srinivasan A, McLaughlin L, Wang C, et al. Early infections after autologous hematopoietic stem cell transplantation in children and adolescents: the St. Jude experience. Transpl Infect Dis. 2014; 16(1): 90–97.
- Pasquini MC, Zhu X. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides. https://www.cibmtr.org/Pages/index.aspx (January 01, 2021).
- Sinko J, Csomor J, Barta A, et al. Infection-related deaths in the haematopoietic stem cell transplant setting. Bone Marrow Transplant. 2012; 47(Suppl. 1): abstract 472.
- Bjorklund A, Aschan J, Labopin M, et al. Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation. Bone Marrow Transplant. 2007; 40(11): 1055–1062.
- Martino R, Kerguelen A, Valcárcel D, et al. Reduction of infection-related mortality after allogeneic PBSCT from HLA-identical siblings: longitudinal analysis from 1994 to 2008 at a single institution. Bone Marrow Transplant. 2011; 46(5): 690–701.
- Marr KA, Schlamm HT, Herbrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015; 162(2): 81–89.
- Green ML, Leisenring W, Xie Hu, et al. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016; 3(3): e119–e127.
- Styczyński J. Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation. Acta Haematologica Polonica. 2020; 51(1): 17–23.
- Galazka P, Czyzewski K, Marjanska A, et al. Minimally invasive surgery in pediatric oncology: proposal of guidelines. Anticancer Res. 2019; 39(11): 5853–5859.
- Gałązka P, Redloch K, Kroczek K, et al. Minimally invasive surgery for congenital abdominal cystic lesions in newborns and infants. In Vivo. 2020; 34(3): 1215–1221.
- Styczynski J, Tridello G, Gil L, et al. Prognostic impact of Epstein-Barr virus serostatus in patients with nonmalignant hematological disorders undergoing allogeneic hematopoietic cell transplantation: the study of Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation. Acta Haematologica Polonica. 2020; 51(2): 73–80.
- Garcia-Vidal C, Upton A, Kirby KA, et al. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis. 2008; 47(8): 1041–1050.
