Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B

Blood. 1998 Oct 15;92(8):2719-24.

Abstract

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with complete absence or malfunction of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagocytic cells. Life-threatening infections especially with aspergillus are common despite optimal antimicrobial therapy. Bone marrow transplantation (BMT) is contraindicated during invasive aspergillosis in any disease setting. We report an 8-year-old patient with CGD who underwent HLA-genoidentical BMT during invasive multifocal aspergillus nidulans infection, nonresponsive to treatment with amphotericin-B and gamma-interferon. During the first 10 days post-BMT, the patient received granulocyte colony-stimulating factor (G-CSF)-mobilized, 25 Gy irradiated granulocytes from healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the transfused granulocytes. This was confirmed in vitro by apoptosis assays and in vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral blood 12 and 36 hours after the transfusions. Clinical and biological signs of infection began to disappear on day 7 post-BMT. Positron emission tomography with F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months post-BMT showed complete disappearance of infectious foci. At 2 years post-BMT, the patient is well with full immune reconstitution and no sign of aspergillus infection. Our results show that HLA-identical BMT may be successful during invasive, noncontrollable aspergillus infection, provided that supportive therapy is optimal.

Publication types

  • Case Reports

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / therapeutic use*
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Apoptosis
  • Aspergillosis / diagnostic imaging
  • Aspergillosis / drug therapy
  • Aspergillosis / prevention & control
  • Aspergillosis / therapy*
  • Aspergillus nidulans*
  • Bone Marrow Transplantation*
  • Child
  • Combined Modality Therapy
  • Drug Carriers
  • Graft Survival / drug effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Granulocytes / physiology
  • Granulomatous Disease, Chronic / complications
  • Granulomatous Disease, Chronic / therapy*
  • Humans
  • Itraconazole / therapeutic use
  • Leukocyte Count
  • Leukocyte Transfusion*
  • Liposomes
  • Lung Diseases, Fungal / drug therapy
  • Male
  • Tomography, Emission-Computed
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Drug Carriers
  • Liposomes
  • Granulocyte Colony-Stimulating Factor
  • Itraconazole
  • Amphotericin B