Impact of the D-index deduced from duration and intensity of neutropenia following chemotherapy on the risk of invasive fungal infection in pediatric acute myeloid leukemia

  • Hirozumi Sano
  • Ryoji Kobayashi
  • Daisuke Suzuki
  • Daiki Hori
  • Kenji Kishimoto
  • Kunihiko Kobayashi
Original Article
  • 27 Downloads

Abstract

Pediatric patients with acute myeloid leukemia (AML) are at high risk of invasive fungal infection (IFI). In adult patients, the D-index, which reflects the duration and intensity of neutropenia, was reported as a predictive factor of IFI after induction therapy for AML. The aim of this study was to assess whether the D-index is a predictive factor for IFI in pediatric AML. We define the D-index as the area over the neutrophil curve during neutropenia. Ninety-two courses of chemotherapy performed for 24 consecutive patients with AML undergoing chemotherapy at Sapporo Hokuyu Hospital between April 2007 and March 2017 were analyzed. We also evaluated the utility of the cumulative D-index (c-D-index) from the start of neutropenia until the clinical manifestation of IFI in these patients. The D-index and c-D-index were compared between courses with and without IFI episodes. The median D-index and c-D-index in 6 courses with IFI episodes were 12,816 (range 9500–27,412) and 7250 (range 3987–16,273), respectively, which was not statistically higher than the median D-index [10,127 (range 3788–20,897)] in 86 courses without IFI episodes (P = 0.081 and P = 0.108, respectively). Unlike in adult cases, neither the D-index nor c-D-index reflected the risk of IFI in pediatric AML.

Keywords

Acute myeloid leukemia Invasive fungal infection Risk factor Neutropenia D-index 

Abbreviations

AUC

Area under the curve

IFI

Invasive fungal infection

Notes

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

References

  1. 1.
    Cornely OA, Böhme A, Reichert D, Reuter S, Maschmeyer G, Maertens J, et al. Risk factors for breakthrough invasive fungal infection during secondary prophylaxis. J Antimicrob Chemother. 2008;61:939–46.CrossRefPubMedGoogle Scholar
  2. 2.
    Kobayashi R, Kaneda M, Sato T, Ichikawa M, Suzuki D, Ariga T. The clinical feature of invasive fungal infection in pediatric patients with hematologic and malignant diseases: a 10-year analysis at a single institution at Japan. J Pediatr Hematol Oncol. 2008;30:886–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Sung L, Gamis A, Alonzo TA, Buxton A, Britton K, Deswarte-Wallace J, et al. Infections and association with different intensity of chemotherapy in children with acute myeloid leukemia. Cancer. 2009;115:1100–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    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) Consensus Group. Clin Infect Dis. 2008;46:1813–21.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. 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;52:427–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Portugal RD, Garnica M, Nucci M. Index to predict invasive mold infection in high-risk neutropenic patients based on the area over the neutrophil curve. J Clin Oncol. 2009;27:3849–54.CrossRefPubMedGoogle Scholar
  7. 7.
    Sano H, Kobayashi R, Hori D, Kishimoto K, Suzuki D, Yasuda K, et al. Prophylactic administration of voriconazole with two different doses for invasive fungal infection in children and adolescents with acute myeloid leukemia. J Microbiol Immunol Infect (in press).Google Scholar
  8. 8.
    Sato T, Kobayashi R, Yasuda K, Kaneda M, Iguchi A, Kobayashi K. A prospective, randomized study comparing cefozopran with piperacillin-tazobactam plus ceftazidime as empirical therapy for febrile neutropenia in children with hematological disorders. Pediatr Blood Cancer. 2008;51:774–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Sarashina T, Kobayashi R, Yoshida M, Toriumi N, Suzuki D, Sano H, et al. A randomized trial of cefozopran versus cefepime as empirical antibiotic treatment of febrile neutropenia in pediatric cancer patients. Pediatr Blood Cancer. 2014;61:1992–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Sano H, Kobayashi R, Suzuki D, Kishimoto K, Yasuda K, Kobayashi K. Comparison between piperacillin/tazobactam and cefepime monotherapies as an empirical therapy for febrile neutropenia in children with hematological and malignant disorders: a prospective, randomized study. Pediatr Blood Cancer. 2015;62:356–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Sano H, Kobayashi R, Suzuki D, Hori D, Kishimoto K, Kobayashi K. A prospective randomized trial comparing piperacillin/tazobactam with meropenem as empirical antibiotic treatment of febrile neutropenic children and adolescents with hematologic and malignant disorders. Pediatr Blood Cancer. 2017;64:e26360.CrossRefGoogle Scholar
  12. 12.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Suzuki D, Kobayashi R, Hori D, Kishimoto K, Sano H, Yasuda K, et al. Stem cell transplantation for acute myeloid leukemia with pulmonary and cerebral mucormycosis. Pediatr Int. 2016;58:569–72.CrossRefPubMedGoogle Scholar
  14. 14.
    Blijlevens NM, Donnelly JP, de Pauw BE. Impaired gut function as risk factor for invasive candidiasis in neutropenic patients. Br J Haematol. 2002;117:259–64.CrossRefPubMedGoogle Scholar
  15. 15.
    Nucci M, Anaissie E. Revisiting the source of candidemia: skin or gut? Clin Infect Dis. 2001;33:1959–67.CrossRefPubMedGoogle Scholar
  16. 16.
    Dvorak CC, Steinbach WJ, Brown JM, Agarwal R. Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2005;36:621–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Blyth CC, Chen SC, Slavin MA, Serena C, Nguyen Q, Marriott D, et al. Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Pediatrics. 2009;123:1360–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Mor M, Gilad G, Kornreich L, Fisher S, Yaniv I, Levy I. Invasive fungal infections in pediatric oncology. Pediatr Blood Cancer. 2011;56:1092–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Hale KA, Shaw PJ, Dalla-Pozza L, MacIntyre CR, Isaacs D, Sorrell TC. Epidemiology of paediatric invasive fungal infections and a case–control study of risk factors in acute leukaemia or post stem cell transplant. Br J Haematol. 2010;149:263–72.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Hirozumi Sano
    • 1
  • Ryoji Kobayashi
    • 1
  • Daisuke Suzuki
    • 1
  • Daiki Hori
    • 1
  • Kenji Kishimoto
    • 1
  • Kunihiko Kobayashi
    • 1
  1. 1.Department of Hematology/Oncology for Children and AdolescentsSapporo Hokuyu HospitalSapporoJapan

Personalised recommendations