Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B.
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.
Divisions of Immunology/Hematology and Radiology, University Children's Hospital of Zurich, Switzerland.
H
H
Ozsahin
M
M
von Planta
I
I
Müller
H C
HC
Steinert
D
D
Nadal
R
R
Lauener
P
P
Tuchschmid
U V
UV
Willi
M
M
Ozsahin
N E
NE
Crompton
R A
RA
Seger
D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D001228:Aspergillosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*; D001233:Aspergillus nidulans; D016026:Bone Marrow Transplantation; D002648:Child; D003131:Combined Modality Therapy; D004337:Drug Carriers; D006085:Graft Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006098:Granulocytes / Q000502:physiology; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000628:therapy*; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D007958:Leukocyte Count; D017708:Leukocyte Transfusion; D008081:Liposomes; D008172:Lung Diseases, Fungal / Q000188:drug therapy; D008297:Male; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D016179:Granulocyte Colony-Stimulating Factor; D017964:Itraconazole; D000666:Amphotericin B