Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

Turk J Haematol. 2015 Dec;32(4):329-37. doi: 10.4274/tjh.2014.0035. Epub 2015 Apr 27.

Abstract

Objective: Rapid and effective treatment of invasive fungal infection (IFI) in patients with leukemia is important for survival. In this study, we aimed to describe variations regarding clinical features, treatment modalities, time of restarting chemotherapy, and outcome in children with IFI and acute leukemia (AL).

Materials and methods: The charts of all pediatric AL patients in our clinic between the years of 2001 and 2013 were retrospectively reviewed. All patients received prophylactic fluconazole during the chemotherapy period.

Results: IFI was identified in 25 (14%) of 174 AL patients. Most of them were in the consolidation phase of chemotherapy and the patients had severe neutropenia. The median time between leukemia diagnosis and definition of IFI was 122 days. Twenty-four patients had pulmonary IFI. The most frequent finding on computed tomography was typical parenchymal nodules. The episodes were defined as proven in 4 (16%) patients, probable in 7 (28%) patients, and possible in 14 (56%) patients. The median time for discontinuation of chemotherapy was 27 days. IFI was treated successfully in all patients with voriconazole, amphotericin B, caspofungin, or posaconazole alone or in combination. Chemotherapy was restarted in 50% of the patients safely within 4 weeks and none of those patients experienced reactivation of IFI. All of them were given secondary prophylaxis. The median time for antifungal treatment and for secondary prophylaxis was 26 and 90 days, respectively. None of the patients died due to IFI.

Conclusion: Our data show that rapid and effective antifungal therapy with rational treatment modalities may decrease the incidence of death and that restarting chemotherapy within several weeks may be safe in children with AL and IFI.

Amaç: Lösemili hastalarda invaziv fungal enfeksiyonların (İFE) çabuk ve etkin tedavisi sağkalım için önemlidir. Bu çalışmada akut lösemi (AL) ve İFE olan çocuklarda klinik bulgular, tedavi şekilleri, tekrar kemoterapiye başlama zamanı ve tedavi sonucu gibi değişkenleri değerlendirmeyi amaçladık. Gereç ve Yöntemler: Kliniğimizde 2001-2013 yılları arasında izlenmiş tüm AL’lı çocukların hastane kayıtları retrospektif olarak tarandı. Tüm hastalara kemoterapi süresince proflaktik flukonazol tedavisi verildi. Bulgular: İFE, 174 AL hastasından 25’inde (%14) saptandı. Çoğu konsolidasyon tedavisi sırasında gelişmişti ve hastalar ağır nötropenikti. Lösemi tanısı ve İFE gelişme arasındaki ortanca süre 122 gündü. Hastaların 24’ünde pulmoner İFE vardı. Bilgisayarlı tomografi tetkikinde en sık izlenen bulgu parenkimal nodüllerdi. İFE epizodları 4 (%16) olguda kanıtlanmış, 7 (%28) olguda olası, 14 (%56) olguda muhtemel olarak değerlendirildi. Kemoterapiye ara verme süresi ortanca 27 gündü. İFE voriconazole, amphotericin B, caspofungin, posaconazole tekli veya kombine tedavileri ile başarıyla tedavi edildi. Olguların %50’sinde kemoterapiye 4 haftadan önce başlandı ve hiçbirinde İFE reaktivasyonu saptanmadı. Tümüne ikincil proflaksi verildi. Antifungal tedavi ve sekonder proflaksi ortanca süresi sırayla 26 ve 90 gündü. Hastalardan hiçbiri İFE ile kaybedilmedi. Sonuç: Verilerimiz AL ve İFE olan çocuklarda erken ve etkin rasyonel antifungal tedavi ile ölüm oranının azaltılabileceğini ve birkaç hafta içinde kemoterapiye güvenle başlanabileceğini göstermektedir.

MeSH terms

  • Adolescent
  • Antifungal Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Febrile Neutropenia / chemically induced
  • Febrile Neutropenia / complications
  • Female
  • Fluconazole / therapeutic use
  • Humans
  • Immunocompromised Host
  • Infant
  • Invasive Fungal Infections / drug therapy*
  • Invasive Fungal Infections / etiology
  • Invasive Fungal Infections / prevention & control
  • Leukemia, Myeloid, Acute / complications*
  • Leukemia, Myeloid, Acute / drug therapy
  • Lung Diseases, Fungal / drug therapy
  • Lung Diseases, Fungal / etiology
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Retrospective Studies
  • Survival Analysis

Substances

  • Antifungal Agents
  • Fluconazole