Invasive mold disease of the central nervous system in children and adolescents with cancer or undergoing hematopoietic stem cell transplantation: Analysis of 29 contemporary patients

Pediatr Blood Cancer. 2019 Aug;66(8):e27806. doi: 10.1002/pbc.27806. Epub 2019 May 7.

Abstract

Background: Invasive mold disease (IMD) is a severe infectious complication in immunocompromised patients. The outcome of central nervous system (CNS) IMD is poor, but contemporary data, in particular in the pediatric setting, are lacking.

Procedure: For this retrospective multicenter analysis, pediatric patients < 18 years with proven or probable CNS IMD receiving chemotherapy or undergoing allogeneic HSCT were reported by the local investigator. CNS IMD had to be diagnosed between 2007 and 2016. Proven CNS IMD was defined as compatible CNS imaging or macroscopic autopsy findings in conjunction with a positive microscopic or microbiological result in the brain tissue or cerebrospinal fluid. Probable CNS IMD was defined as compatible CNS imaging findings in combination with proven or probable IMD at a site outside the CNS.

Results and conclusions: A total of 29 patients (median age, 14 years; 14 allogeneic HSCT recipients) were diagnosed with proven (n = 12) or probable (n = 17) CNS IMD. Aspergillus spp. was the most common fungal pathogen. All but one patient had IMD sites outside the CNS and eight patients (27.6%) were neurologically asymptomatic at diagnosis of CNS IMD. Forty-nine percent of the patients survived CNS IMD; however, 46.7% of the survivors suffered from severe long-term neurological sequelae. Our data suggest that (1) outcome of CNS IMD has improved in children as compared with previous series, (2) half of surviving patients suffer from severe neurological sequelae, and (3) imaging of the CNS should be performed in all children with IMD irrespective of neurological symptoms.

Keywords: central nervous system; children; fungal infection; late sequelae; mold.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Central Nervous System Diseases / pathology
  • Central Nervous System Diseases / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Incidence
  • Infant
  • Invasive Fungal Infections / epidemiology*
  • Invasive Fungal Infections / etiology
  • Invasive Fungal Infections / microbiology
  • Male
  • Prognosis
  • Retrospective Studies
  • Survival Rate