Download PDF
Klin Padiatr 2012; 224(03): 160-165
DOI: 10.1055/s-0032-1304625
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Invasive Aspergillosis in Pediatric Oncology Patients: A Rare Event With Poor Prognosis – Case Analysis to Plan Better Targeted Prophylactic or Therapeutic Measurement

Invasive Aspergillose bei pädiatrischen hämatoonkologischen Patienten: Eine seltene Erkrankung mit schlechter Prognose – Eine Fallanalyse zur Planung von besser gezielten prophylaktischen und therapeutischen Maßnahmen
F. Babor
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
F. Schuster
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
C. Mackenzie
2   Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine-University, Duesseldorf, Germany
,
R. Meisel
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
J. Schaper
3   Institute of Radiology, Heinrich Heine-University, Duesseldorf, Germany
,
H. Sabir
4   Department of General Pediatrics, Heinrich Heine-University, Duesseldorf, Germany
,
M. Siepermann
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
R. Wessalowski
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
G. Janßen
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
A. Borkhardt
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
,
H.-J. Laws
1   Department of Pediatric Oncology, Hematology and Immunology, Center for Child and Adolescent Health, Heinrich-Heine-University, Duesseldorf, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
13 April 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Background:

Despite the implementation of new antifungal drugs, invasive aspergillosis (IA) still remains a considerable challenge in pediatric oncology with a severe mortality. Prophylactic and therapeutic measurement have to be evaluated in these rare but poor prognostic patients. Therefore the entire group of patients at risk of developing IA has to be defined before cooperative prospective trials.

Methods:

In a retrospective analysis including all our patients with malignancies we looked for patients with proven/probable IA. Cases of the period from 2003 to 2008 were analyzed in detail.

Results:

In the period between 2003 to 2008 24 of 755 patients were affected by proven/ probable IA. Compared to former studies incidence increased from 1.3%in 1980 to 3.4% in 2008. AML patients with or without allogeneic/haploidentical stem cell transplantation were at highest risk (24% and 25% respectively, in comparison to 1% in ALL-patients). Survival after 2 years was 50% for patients with AML and IA.

Conclusion:

In patients with high risk to develop IA the effect of intensified, intravenous antimycotic prophylaxis has to be proven prospectively in a cooperative and randomized setting.

Zusammenfassung

Hintergrund:

Trotz der Einführung neuer antimykotischer Medikamente ist die invasive Aspergillose (IA) nach wie vor ein beträchtlicher Risikofaktor in der pädiatrischen Onkologie mit einer erheblichen Mortalitätsrate. Prophylaktische und therapeutische Maßnahmen müssen in dieser seltenen, aber prognostisch ungünstigen Patientengruppe untersucht werden. Zu diesem Zweck sollte zuvor die gesamte Risikogruppe für kooperative prospektive klinische Studien klar definiert sein.

Methode:

In einer retrospektiven Analyse aller pädiatrischen Patienten mit Malignomen wurden alle Patienten mit gesicherter/wahrscheinlicher IA identifiziert und analysiert, die zwischen 2003 und 2008 behandelt wurden. Ergebnisse: Im Zeitraum von 2003 bis 2008 waren 24 von 755 behandelten Patienten von einer gesicherten/wahrscheinlichen IA betroffen. Im Vergleich zu einer früheren Analyse stieg die Inzidenz der IA von 1.3% im Jahr 1980 auf jetzt 3.4%. Bei AML-Patienten mit allogener/haploidenter und ohne allogene/haploidente Stammzelltransplantation war das Risiko am größten (24% bzw. 25% verglichen mit 1% bei ALL Patienten). Die Überlebensrate nach 2 Jahren betrug 50% in der Gruppe der AML-Patienten.

Schlussfolgerung:

Bei Patienten mit hohem Risiko für IA erscheint eine kontinuierliche, intravenöse antimykotische Prophylaxe essenziell und ist prospektiv in kooperativen, randomisierten Studien zu prüfen.

Key words

Aspergillosis - acute leukemia - children - fungal infection

Schlüsselwörter

Pilzinfektion - Aspergillus - Kinder - Onkologie - Leukämie - Transplantation
 

  • References

  • 1 Abbasi S, Shenep JL, Hughes WT et al. Aspergillosis in children with cancer: A 34-year experience. Clin Infect Dis 1999; 29: 1210-1219
    CrossrefPubMedGoogle Scholar
  • 2 Andriole VT. Infections with Aspergillus species. Clin Infect Dis 1993; 17 (Suppl. 02) S481-S486
    CrossrefPubMedGoogle Scholar
  • 3 Ascioglu S, Rex JH, de Pauw B et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34: 7-14
    CrossrefPubMedGoogle Scholar
  • 4 Bochennek KTL, Schedler N, Becker M et al. Alternierende Gaben von liposomalem Amphothericin B (LAmB) zur Pilzprophylaxe bei Kindern mit Hochrisiko-Leukämie. Klin Padiatr 2010; 222 (Suppl. 01) S8 DOI: 10.1055/s-0030-1261304.
    PubMedGoogle Scholar
  • 5 Bohme 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
    CrossrefPubMedGoogle Scholar
  • 6 Burgos A, Zaoutis TE, Dvorak CC et al. Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases. Pediatrics 2008; 121: e1286-e1294
    CrossrefPubMedGoogle Scholar
  • 7 Cornely OA, Bohme A, Buchheidt D et al. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 2009; 94: 113-122
    CrossrefPubMedGoogle Scholar
  • 8 Cornet M, Fleury L, Maslo C et al. Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. J Hosp Infect 2002; 51: 288-296
    CrossrefPubMedGoogle Scholar
  • 9 Crassard N, Hadden H, Pondarre C et al. Invasive aspergillosis and allogeneic hematopoietic stem cell transplantation in children: a 15-year experience. Transpl Infect Dis 2008; 10: 177-183
    CrossrefPubMedGoogle Scholar
  • 10 De Pauw B, 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: 1813-1821
    CrossrefPubMedGoogle Scholar
  • 11 Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis 1996; 23: 608-615
    CrossrefPubMedGoogle Scholar
  • 12 Denning DW. Invasive aspergillosis. Clin Infect Dis 1998; 26: 781-803 quiz 804-785
    CrossrefPubMedGoogle Scholar
  • 13 Denning DW, Marinus A, Cohen J et al. An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: diagnosis and therapeutic outcome. EORTC Invasive Fungal Infections Cooperative Group. J Infect 1998; 37: 173-180
    CrossrefPubMedGoogle Scholar
  • 14 Gobel V, Jurgens H, Thomas L et al. Microbial spectrum of blood and body cultures in febrile episodes of children under chemotherapy for treatment of malignant diseases. Pediatr Hematol Oncol 1987; 4: 7-13
    CrossrefPubMedGoogle Scholar
  • 15 Groll AH, Kurz M, Schneider W et al. Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival. Mycoses 1999; 42: 431-442
    CrossrefPubMedGoogle Scholar
  • 16 Groll AH, Ritter J. Diagnosis and management of fungal infections and pneumocystis pneumonitis in pediatric cancer patients. Klin Padiatr 2005; 217 (Suppl. 01) S37-S66
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Groll AH, Shah PM, Mentzel C et al. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 1996; 33: 23-32
    CrossrefPubMedGoogle Scholar
  • 18 Groll AS, NL Walsh TJ. et al. Micafungin – Overview of efficacy in pediatric patients. Klin Padiatr 2010; 222 (Suppl. 01) S48 DOI: 10.1055/s-0030-1261435.
    PubMedGoogle Scholar
  • 19 Haase R, Lieser U, Kramm C et al. Management of oncology patients admitted to the paediatric intensive care unit of a general children’s hospital – a single center analysis. Klin Padiatr 2011; 223: 142-146
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Herbrecht R, Denning DW, Patterson TF et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347: 408-415
    CrossrefPubMedGoogle Scholar
  • 21 Hovi L, Saarinen-Pihkala UM, Vettenranta K et al. Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years. Bone Marrow Transplant 2000; 26: 999-1004
    CrossrefPubMedGoogle Scholar
  • 22 Kaya Z, Gursel T, Kocak U et al. Invasive fungal infections in pediatric leukemia patients receiving fluconazole prophylaxis. Pediatr Blood Cancer 2009; 52: 470-475
    CrossrefPubMedGoogle Scholar
  • 23 Laws HJ, Schneider DT, Janssen G et al. Trends in infections in children with malignant disease in 2000: comparison of data of 1980/81. Pediatr Hematol Oncol 2007; 24: 343-354
    CrossrefPubMedGoogle Scholar
  • 24 Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32: 358-366
    CrossrefPubMedGoogle Scholar
  • 25 McNeil MM, Nash SL, Hajjeh RA et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997. Clin Infect Dis 2001; 33: 641-647
    CrossrefPubMedGoogle Scholar
  • 26 Rubio PM, Sevilla J, Gonzalez-Vicent M et al. Increasing incidence of invasive aspergillosis in pediatric hematology oncology patients over the last decade: a retrospective single centre study. J Pediatr Hematol Oncol 2009; 31: 642-646
    CrossrefPubMedGoogle Scholar
  • 27 Sulahian A, Boutboul F, Ribaud P et al. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Cancer 2001; 91: 311-318
    CrossrefPubMedGoogle Scholar
  • 28 Thomas L, Baggen L, Chisholm J et al. Diagnosis and treatment of aspergillosis in children. Expert Rev Anti Infect Ther 2009; 7: 461-472
    CrossrefPubMedGoogle Scholar
  • 29 Vohringer S, Schrum J, Ott H et al. Severe phototoxicity associated with long-term voriconazole treatment. J Dtsch Dermatol Ges 2011; 9: 274-276
    PubMedGoogle Scholar
  • 30 Walmsley S, Devi S, King S et al. Invasive Aspergillus infections in a pediatric hospital: a ten-year review. Pediatr Infect Dis 1993; 12: 673-682
    PubMedGoogle Scholar
  • 31 Wheat LJ, Walsh TJ. Diagnosis of invasive aspergillosis by galactomannan antigenemia detection using an enzyme immunoassay. Eur J Clin Microbiol Infect Dis 2008; 27: 245-251
    CrossrefPubMedGoogle Scholar