Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Childhood AML

Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93

Abstract

Infections still remain a major cause of therapy-associated morbidity and mortality in children with acute myeloid leukemia (AML). To improve supportive care measurements, detailed information on frequency and characteristic features of infectious complications is needed. We retrospectively analyzed the medical charts of 304 children, treated in 30 hospitals according to the multi-institutional clinical trial AML-BFM 93. Overall, 855 infectious complications occurred in 304 patients (fever without identifiable source (n=523; 61.2%), clinically (n=57; 6.7%) and microbiologically documented infections (n=275; 32.1%)). Neutropenia was present in 74.1% of the infectious episodes. In all, 20 patients died of infection-associated complications (15/276 (5.4%) patients without and 5/28 (17.9%) with Down syndrome), most of them during early induction therapy (n=11). Blood stream infections occurred in 228 episodes (Gram-positive (n=202) and Gram-negative (n=42) pathogens). Invasive fungal infection was probable or proven in 15 patients. In 113 out of the 855 infectious episodes (13.3%), pneumonia was radiologically diagnosed. Better strategies of supportive care might help to improve overall survival in children undergoing chemotherapy for AML. Therefore, children with AML should be treated in specialized pediatric centers, and there should be a very low threshold to readmit patients, in particular patients with pulmonary symptoms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Creutzig U, Ritter J, Zimmermann M, Reinhardt D, Hermann J, Berthold F et al. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia–Berlin–Frankfurt–Munster 93. J Clin Oncol 2001; 19: 2705–2713.

    Article  CAS  Google Scholar 

  2. Feusner JH, Hastings CA . Infections in children with acute myelogenous leukemia. Concepts of management and prevention. J Pediatr Hematol Oncol 1995; 17: 234–247.

    Article  CAS  Google Scholar 

  3. Tobias JS, Wrigley PF, O'Grady F . Bacterial infection and acute myeloblastic leukaemia: an analysis of two hundred patients undergoing intensive remission induction therapy. Eur J Cancer 1978; 14: 383–391.

    Article  CAS  Google Scholar 

  4. Madani TA . Clinical infections and bloodstream isolates associated with fever in patients undergoing chemotherapy for acute myeloid leukemia. Infection 2000; 28: 367–373.

    Article  CAS  Google Scholar 

  5. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB . Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis 2003; 36: 1103–1110.

    Article  Google Scholar 

  6. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F 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.

    Article  CAS  Google Scholar 

  7. Creutzig U, Ritter J, Zimmermann M, Hermann J, Gadner H, Blütters-Sawatzki D et al. Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group. Leukemia 2001; 15: 348–354.

    Article  CAS  Google Scholar 

  8. Creutzig U, Ritter J, Vormoor J, Ludwig WD, Niemeyer C, Reinisch I et al. Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group. Leukemia 1996; 10: 1677–1686.

    CAS  PubMed  Google Scholar 

  9. Auletta JJ, O'Riordan MA, Nieder ML . Infections in children with cancer: a continued need for the comprehensive physical examination. J Pediatr Hematol Oncol 1999; 21: 501–508.

    Article  CAS  Google Scholar 

  10. Riley LC, Hann IM, Wheatley K, Stevens RF . Treatment-related deaths during induction and first remission of acute myeloid leukaemia in children treated on the Tenth Medical Research Council acute myeloid leukaemia trial (MRC AML10). The MCR Childhood Leukaemia Working Party. Br J Haematol 1999; 106: 436–444.

    Article  CAS  Google Scholar 

  11. Pizzo PA, Robichaud KJ, Wesley R, Commers JR . Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes. Medicine (Baltimore) 1982; 61: 153–165.

    Article  CAS  Google Scholar 

  12. Lehrnbecher T, Foster C, Vazquez N, Mackall CL, Chanock SJ . Therapy-induced alterations in host defense in children receiving chemotherapy. J Pediatr Hematol Oncol 1997; 19: 399–417.

    Article  CAS  Google Scholar 

  13. Tunkel AR, Sepkowitz KA . Infections caused by viridans streptococci in patients with neutropenia. Clin Infect Dis 2002; 34: 1524–1529.

    Article  Google Scholar 

  14. Cordonnier C, Buzyn A, Leverger G, Herbrecht R, Hunault M, for the Club de Réflexion sur les Infections en Onco-Hématologie et al. Epidemiology and risk factors for Gram-positive coccal infections in neutropenia: toward a more targeted antibiotic strategy. Clin Infect Dis 2003; 36: 149–158.

    Article  Google Scholar 

  15. Rieske K, Handrick W, Spencker FB, Gunther E . Infection caused by viridans streptococci in children with malignant hematologic diseases. Klin Padiatr 1997; 209: 364–372.

    Article  CAS  Google Scholar 

  16. Shenep JL . Viridans-group streptococcal infections in immunocompromised hosts. Int J Antimicrob Agents 2000; 14: 129–135.

    Article  CAS  Google Scholar 

  17. Woods WG, Ruymann FB, Lampkin BC, Buckley JD, Bernstein ID, Srivastava AK et al. The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia. Cancer 1990; 66: 1106–1113.

    Article  CAS  Google Scholar 

  18. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP . Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999; 29: 239–244.

    Article  CAS  Google Scholar 

  19. Ritter J, Roos N . Special aspects related to invasive fungal infections in children with cancer. In: F. Meunier (ed) Invasive Fungal Infections in Cancer Patients. London, Philadelphia, Sydney, Tokyo, Toronto: Balliere Tindall, 1995, pp 179–204.

    Google Scholar 

  20. Zubizarreta P, Felice MS, Alfaro E, Fraquelli L, Casak S, Quinteros R et al. Acute myelogenous leukemia in Down's syndrome: report of a single pediatric institution using a BFM treatment strategy. Leukemia Res 1998; 22: 465–472.

    Article  CAS  Google Scholar 

  21. Taub JW, Stout ML, Buck SA, Huang X, Vega RA, Becton DL et al. Myeloblasts from Down syndrome children with acute myeloid leukemia have increased in vitro sensitivity to cytosine arabinoside and daunorubicin. Leukemia 1997; 11: 1594–1595.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Deutsche Krebshilfe. We thank the medical and nursing staff of the participating centers. This work is dedicated to Professor Joachim Kühl.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T Lehrnbecher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lehrnbecher, T., Varwig, D., Kaiser, J. et al. Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93. Leukemia 18, 72–77 (2004). https://doi.org/10.1038/sj.leu.2403188

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403188

Keywords

This article is cited by

Search

Quick links