Immunomodulation with Interferon-Gamma and
Colony-Stimulating Factors for Refractory Fungal
Infections in Patients with Leukemia
M. Cecilia Dignani, M.D.1
John H. Rex, M.D.2
Ka-Wah Chan, M.D.3
Gordon Dow, M.D.4
Margarida deMagalhaes-Silverman, M.D.5
AnneMarie Maddox, M.D.6
Thomas Walsh, M.D.7
Elias Anaissie, M.D.1
1Division of Supportive Care, Myeloma Institute for
Research and Therapy, University of Arkansas for
Medical Sciences, Little Rock, Arkansas.
2Centers for Infectious Diseases, University of
Texas Medical School, Houston, Texas.
3Department of Pediatrics, The University of Texas
M. D. Anderson Cancer Center, Houston, Texas.
4Department of Infectious Diseases, The Moncton
Hospital, Moncton, New Brunswick, Canada.
5Department of Internal Medicine, Division of He-
matology and Oncology, School of Medicine, Uni-
versity of Iowa, Iowa City, Iowa.
6Division Hematology and Oncology, Department
of Internal Medicine, University of Arkansas for
Medical Sciences, Little Rock, Arkansas.
7Immunocompromised Host Section, National
Cancer Institute, National Institutes of Health, Be-
M.C. Dignani’s current address: Infectious Dis-
eases FUNDALEU (Foundation for the Fight Against
Leukemia), Buenos Aires, Argentina.
J. H. Rex’s current address: AstraZeneca, Alderley
Park, Macclesfield Chesire, SK10 4TF United Kingdom.
Address for reprints: Elias J. Anaissie, M.D., Divi-
sion of Supportive Care, Myeloma Institute for
Research and Therapy, Arkansas Cancer Research
Center, University of Arkansas for Medical Sci-
ences, 4301 West Markham, Mail Slot 776, Little
Rock, AR 72205; Fax: (501) 686-6442; E-mail:
Received June 25, 2004; revision received March
7, 2005; accepted March 10, 2005.
*This article is a US Government work and, as
such, is in the public domain in the United States
BACKGROUND. Invasive fungal infections (IFI) in immunocompromised patients
are associated with significant morbidity and mortality, despite appropriate anti-
fungal treatment and recovery from neutropenia. The outcome of these infections
depends significantly on the overall state of immunosuppression, including mainly
the phagocytic system (neutrophils and macrophages). Interferon-gamma (IFN-?),
granulocyte-colony—stimulating factor (G-CSF) and granulocyte-macrophage—
colony-stimulating factor (GM-CSF) are cytokines that enhance the activity of
neutrophils and macrophages.
METHODS. The authors reported 4 patients with leukemia and refractory invasive
candidiasis or trichosporonosis despite 1–13 months of appropriate antifungal
RESULTS. Cytokines were administered for 1.5–5 months without significant tox-
icity. For each patient, initiation of interferon-gamma plus a colony-stimulating
factor resulted in a clinical response. The contribution of cytokines to control the
fungal infection in these 4 patients was suggested by the strong inflammatory
reaction observed in the 2 patients who had an immediate response (within 7 days
of initiation of cytokine therapy) and by the good outcome in the 2 other patients
in whom antifungal agents were discontinued at the start of cytokine therapy.
CONCLUSIONS. These data suggested a potential role for immunomodulation in
patients with leukemia with refractory invasive fungal infections. Cancer 2005;104:
199–204. Published 2005 by the American Cancer Society.*
KEYWORDS: leukemia, candidiasis, interferon-gamma, fungal infections.
early institution of appropriate antifungal treatment and recovery
from neutropenia. The outcome of these infections depends signifi-
cantly on the overall state of immunosuppression.1
The phagocytic system (neutrophils and macrophages) consti-
tutes an important defense against opportunistic fungal infection.
Interferon-gamma (IFN-?), granulocyte-colony—stimulating factor
(G-CSF) and granulocyte-macrophage—colony-stimulating factor
(GM-CSF) are cytokines that enhance the activity of neutrophils and
macrophages and may, therefore, enhance the response to fungal
Since 1992, we began utilizing cytokines as salvage therapy for
refractory IFI in patients with cancer with adequate neutrophil counts
and remission of their underlying disease. Complete data were avail-
able for four patients. We report the response of these four patients to
IFN-? and a CSF.
nvasive fungal infections (IFI) in immunocompromised patients are
associated with significant morbidity and mortality, even with the
Published 2005 by the American Cancer Society*
Published online 31 May 2005 in Wiley InterScience (www.interscience.wiley.com).
MATERIALS AND METHODS
The clinical courses of the 4 patients with refractory
IFI is summarized in Table 1. Patient 1 is a 14-year-old
female with acute myeloid leukemia (AML) who de-
veloped chronic disseminated candidiasis (CDC) dur-
ing disease remission induction chemotherapy with
right upper quadrant pain, increased levels of serum
alkaline phosphatase (AP) and bilirubin, and liver and
spleen lesions as observed on computed tomographic
(CT) scan images. After 5 months of antifungal treat-
ment with amphotericin B (AMB) (total dose 3.4 g) and
fluocytosine (5-FC), her condition improved and she
received maintenance therapy with fluconazole. After
receiving 1 month of fluconazole, she developed re-
current hepatosplenic lesions. Antifungal treatment
was changed to AMB and then to amphotericin B lipid
complex (ABLC) plus flucytosine (5-FC) and the pa-
tient underwent splenectomy and partial hepatec-
tomy. Both tissue samples revealed fungal granulomas
and yeast infections but cultures were negative. The
clinical and radiologic findings resolved after 3
months of therapy (? 30 g total dose of ABLC) and
5-FC and fluconazole maintenance was resumed. Two
months later, and while receiving fluconazole, the pa-
tient developed weight loss, increased serum levels of
AP, and liver lesions as observed on CT scan images.
She was considered refractory to antifungal agents
(total of 11 months), fluconazole was discontinued,
and cytokine therapy was initiated with 100 ?g IFN-?
plus 250 ?g/m2GM-CSF 3 times a week. No other
antifungal agent was added. A clear and rapid re-
sponse ensued with normalization of AP serum levels
and ? 90% resolution of the hepatic lesions was ob-
served on CT scan images obtained 30 days after ini-
tiating cytokine therapy. Complete resolution of liver
lesions was documented 17 days after the end of cy-
tokine therapy (EOT), which was received for a total of
2 months. The patient also regained her usual weight
3 months after EOT and was well and free of leukemia
and candidiasis 3 years after EOT.
Patient 2 is a 22-year-old male with acute lympho-
cytic leukemia who developed disseminated Trichos-
poron beigelii infection during disease remission in-
duction chemotherapy with fever, multiple skin
lesions, acute respiratory distress syndrome (ARDS),
and multiorgan failure. The organism was recovered
Characteristics of Patients with Refractory Fungal Infections Treated with Cytokines.
Age (yrs)/gender Malignancy and treatmentFungal infection
Antifungal treatment received
before cytokine therapy
Cytokines and changes in
Outcome after cytokine therapy
Day of first sign of response
Last follow up
11 mos AMB (3.4 g) ? 5- FC (5
mo) Fluconazole (1 mo)
ABLC (? 30 g) ? 5-FC (3
mo) Fluconazole (2 mo)
IFN-? 100 ?g ? GM-CSF
250 ?g/m23 ? wk for 2
3 yrs after EOT: alive and well
without leukemia or
1 yr after EOT: allogeneic
BMT for recurrent leukemia;
died with liver veno-occlusive
disease without infection.
4 yrs after EOT: alive and well
3 mo AMB-ABLC (21 g) ?
fluconazole (3 mo) ? 5-FC
(34 days) AMB ocular
IFN-? 100 ?g/day ?GM-
CSF 500 ?g/day for 6
wks. ABLC, 5-FC, and
6 mo ABCD (11 g), AMB (1.6 g)
Itraconazole (1 mo)
Fluconazole ? 5-FC (1 mo)
IFN-? 50 ?g/m2? G-CSF
5 ?g/kg ? 3/wk. G-CSF
given for 4 mo and
IFN-? for 5 mo. 5-FC
decreased from 400 to
IFN-? 50 ?g/m2? GM-
CSF 250 ?g/day ? 3/
wk for 3 mo.
from 400 to 800 mg/
2 mo AMB (0.2 g)-/-ABLC (?
15 g) ? fluconazole (2 mo)
3 mo after EOT: no infection.
Death from recurrent
leukemia after allogeneic
wk: week; mos: months; 5-FC: 5-fluorocytosine; ABCD: amphotericin B colloidal dispersion; ABLC: amphotericin B lipid complex; ALL: acute lymphocytic leukemia; AMB: amphotericin B deoxycholate; AML: acute
myeloid leukemia; BMT: bone marrow transplantation; EOT: end of treatment; G-CSF: granulocyte—-colony-stimulating factor; GM-CSF: granulocyte-macrophage—-colony-stimulating factor; GVHD: graft vs host
disease; IFN-?: interferon-gamma; L-AMB: liposomal amphotericin B.
200CANCER July 1, 2005 / Volume 104 / Number 1
from a skin biopsy sample, blood cultures, and from
bronchoalveolar lavage specimens. Despite recovery
from neutropenia and treatment with AMB then ABLC
plus fluconazole and GM-CSF, fever persisted and new
splenic lesions developed as observed on CT scan
images. 5-FC was added for 14 days and he underwent
a splenectomy. Histopathologic evaluation yielded
fungal granulomas and T. beigelii infection. One
month later, he developed infection-related hypercal-
cemia and fungal endophthalmitis, leading to the re-
sumption of 5-FC and the intraocular administration
of AMB for an additional month but without resolu-
tion of fever, pulmonary infiltrates, endophthalmitis,
and hypercalcemia. The patient was considered re-
fractory to 3 months of antifungal therapy including
21 g of ABLC, 34 days of 5-FC, and 3 months of
fluconazole. All antifungal agents were discontinued
and cytokine therapy was initiated with 100 ?g/d
IFN-? plus 500 ?g/d GM-CSF. Within the first 30 days
of therapy, a clear response was observed with defer-
vescence and resolution of fever, endophthalmitis, hy-
percalcemia, and pulmonary lesions. A second course
of antineoplastic chemotherapy was given without re-
currence of infection. One year later, the patient un-
derwent matched related donor allogeneic bone mar-
row transplantation (MRD BMT) because of recurrent
leukemia and he died 3 months after transplantation
with veno-occlusive disease of the liver but without
clinical or laboratory evidence of fungal infection. An
autopsy was not performed.
Patient 3 is a 15-year-old female with AML who
developed CDC by Candida tropicalis and sinopulmo-
nary mold infection (organism present on histopathol-
ogy but without growth) after neutropenia related to
an MRD BMT. This patient with CDC presented with
candidemia, and kidney and liver lesions as observed
on CT scan images. Treatment with amphotericin B
colloidal dispersion (ABCD) plus G-CSF–elicited gran-
ulocyte transfusions was started with resolution of
kidney lesions, stabilization of hepatic lesions, but
with persistence of sinopulmonary mold infection. Be-
cause of acute and chronic graft versus host disease
(GVHD), she received maintenance therapy with AMB
(total of 1.6 g) then ABCD (11.3 g). While receiving
ABCD, she developed asthenia, a low-grade fever, in-
fection-related hypercalcemia, and necrotic lymphad-
enitis by Candida spp. ABCD was discontinued and
oral itraconazole was given for 1 month followed by
another month of fluconazole plus 5-FC without re-
sponse (fever, asthenia, hypercalcemia, purulent
lymphadenitis, and recurrence of kidney lesions). She
was considered refractory to 8 months of antifungal
therapy. 5-FC was discontinued, the fluconazole daily
dose was reduced from 400 mg to 200 mg, and cyto-
kine therapy was initiated with 50 ?g/m2IFN-? plus 5
?g/kg G-CSF 3 times a week. Within 7 days of cytokine
therapy, the patient had a remarkable response with
resolution of fever, hypercalcemia, anorexia, and as-
thenia and cessation of drainage at the site of lymph-
adenitis. Fluconazole was discontinued 2 months after
the start of cytokine therapy and she continued to
receive G-CSF and IFN-? for a total of 4 and 5 months,
respectively. A repeat CT scan after 4 months of cyto-
kine therapy revealed stable kidney lesions but signif-
icantly larger liver lesions. Because of the absence of
any clinical or laboratory evidence of infection, and
the excellent performance status of the patient, no
additional treatment was given. Four years after the
EOT, the patient was free of infection despite persis-
tence of chronic GVHD.
Patient 4 is a 28-year-old male with AML who
developed CDC during chemotherapy-related neutro-
penia with fever, ARDS, renal failure, increase serum
levels of AP and bilirubin, and liver and spleen lesions
as observed on magnetic resonance imaging and CT
scan images. Despite recovery from neutropenia and
treatment with AMB followed by ABLC (total dose
? 15 g) plus fluconazole for 2 months, he continued to
have fever, anorexia, bilateral pulmonary infiltrates,
and multiple liver and splenic lesions. A lung biopsy
revealed granulomatous inflammation, and inflam-
mation and fibrosis were observed on the fine-needle
aspiration biopsy liver specimens. ABLC was discon-
tinued, the fluconazole daily dose was increased from
400 mg to 800 mg, and cytokine therapy was initiated
with 50 ?g/m2IFN-? plus 250 ?g/d GM-CSF 3 times a
week. A clear response was observed 7 days after be-
ginning cytokine therapy with a dramatic improve-
ment in his performance status and anorexia but he
developed purulent inguinal lymphadenitis on Day 14
of cytokine therapy. The lymphadenitis was drained
surgically, and histopathologic evaluation revealed in-
flammation, necrosis, and yeast infection. On Day 21
of therapy, a CT scan revealed resolution of the pul-
monary infiltrates but an increase in the number of
hepatic and splenic lesions as his clinical condition
continued to improve. Fluconazole and cytokines
were discontinued 1 week and 3 months later, respec-
tively, and the patient underwent a matched unrelated
BMT. Despite the development of acute GVHD and
the administration of high doses of corticosteroids, he
remained free of fungal infection 3 months after dis-
continuation of cytokine therapy but died of recurrent
leukemia. An autopsy was not performed.
These 4 patients responded promptly (as early
as 7 days) to cytokine therapy and the response in
Patients 3 and 4 was associated with an inflamma-
tory reaction (increase in size and/or number of
IFN-? and CSF for Fungal Infections/Dignani et al. 201
hepatic and splenic lesions, suppurative lymphade-
nitis). Patients 2, 3, and 4 were subsequently chal-
lenged with additional immunosuppression after
discontinuation of cytokine therapy (allogeneic
BMT [Patients 2 and 4] and chronic GVHD [Patient
3]) without recurrence of fungal infection. It is note-
worthy that all antifungal agents were discontinued
in Patients 1 and 2 at the start of cytokine therapy
because of persistent infection despite several
months of appropriate antifungal therapy. Cytokine
therapy was well tolerated without dose reduction
or drug discontinuation because of toxicity. Patient
3 who had active and chronic GVHD at the time of
initiation of cytokine treatment did not have exac-
erbation of GVHD.
The current, small pilot study describes the response
of four patients with leukemia with refractory invasive
yeast infections to cytokine treatment, including two
patients who responded to therapy with cytokines
alone. Three patients received GM-CSF (Patients 1, 2,
and 4) and 1 patient received G-CSF (Patient 3) in
combination with IFN-?. We did not use GM-CSF in
Patient 3 because of the presence of chronic GVHD
and concerns that the combination of two proinflam-
Patients with Refractory Fungal Infections Treated with Cytokines: a Literature Review
Patient age (yrs)/gender
Disease Fungal infectionCytokine therapy Outcome after cytokine therapy
Pneumonia and bronchopleural fistula by Aspergillus-fumigatus
untreated for 2 ys. Not candidate for surgery. Refractory to
6-mo AMB ? short-course 5-FC. (?) Clinical findings ?
increased ESR) and (?) uptake in right lung, chest wall, ribs
Disseminated Pseudallescheria boydii (lungs, scalp, spine,
spinal wound) refractory to 4 mo of miconazole, 3 mo of
ketoconazole, and surgery on thoracic and lumbar vertebrae.
Fever ? spinal wound abscess ? emesis ? increased
Pneumonia and osteomyelitis by A. fumigatus. No response to
5 wks AMB. Fever, radiologic evidence of progression of
osteomyelitis ? increased ESR and increased CRP
IFN-? (?g/m2? 3/wk): 50 ? 3 mo,
100 ? 2 mo, 150 ? 21 mo. AMB
10 mo, then, itraconazole
Mo 8: marked decreased67Ga
scan accumulation and
increased ESR. Mo 26: stable.
IFN-? 50 ?g/m2? 3/wk lifelong.
Miconazole ? 22 days.
Mo 4: clinical, microbiologic,
and radiologic improvement.
4 yrs after EOT: no infection.
IFN-? 50 ?g/m2? 3/wk ? 6 wks.
AMB stopped, itraconazole
Wk 5: afebrile, improvement of
pneumonia and osteomyelitis,
decreased. ESR and CRP. Mo
18 after EOT: asymptomatic
Wk 1: clinical improvement. Wk
3: CT scan: increased liver
lesions. Wk 6: resolution of
liver lesions. Wk 7 after EOT:
recurrent leukemia. No
No additional disease
Day 4: decreased CRP. Day 14:
resolution fever, hypoxia. Day
18: chemotherapy without
infection recurrence. AML
recurrence and death. No
Wk 4: Marked decreased
abdominal, pulmonary, and
neurologic abscesses. Mo 11
after EOT: alive. No infection.
Mo 1: improvement. Extubated
and transferred to a
rehabilitation center with
receipt of fluconazole.
Hepatosplenic Blastoschizomyces capitatus infection. No
response to 3.5 mo AMB then 30 g ABLC. Abdominal pain ?
increased size of liver lesions on CT scan.
IFN-? 54 ?g/m2qod ? 4 wks, then
daily ? 2 wks. Continued ABLC
? 6 wks.
AML post chemotherapy6
Multiple recurrent brain abscesses by A. fumigatus despite 8
surgical procedures, AMB, and itraconazole.
Pneumonia by Aspergillus spp. progressed despite recovery
from neutropenia, AMB and L-AMB. Recurrent cerebellar
abscesses. Poor performance status, increasing CRP,
IFN-? 50 ?g/m2? 3/wk,
IFN-? 60 ?g/m2/day ? 10 days.
AML post chemotherapy9
Disseminated Blastoschizomyces capitatus infection (blood,
lungs, kidneys, spleen, liver, and central nervous system).
Persistence of clinic radiologic signs of infection after 3 mo
AMB (TD 2.2g) ? 5-FC.
Disseminated coccidioidomycosis after receipt of mechanical
ventilator care for respiratory failure despite 10 wks of
antifungal treatment that included ABLC, L-AMB ?
fluconazole, and L-AMB ? itraconazole.
GM-CSF 300 ?g 3/wk ? 4 wks,
then, 150 ?g ? 2/wk ? 16 wks.
AMB ? 5 FC ? 4 wks, then, 5-
FC ? 16 wks.
IFN-? 1b 50 ?g/m2? 3/wk for 9
wks. L-AMB continued
5-FC: 5-flucytosine; ABCD: amphotericin B colloidal dispersion; ABLC: amphotericin B lipid complex; ALL: acute lymphocytic leukemia; AMB: amphotericin B deoxycholate; AML: acute myeloid leukemia; BMT: bone
marrow transplantation; CDC: chronic disseminated candidiasis; CGD: chronic granulomatous disease; CRP: C-reactive protein; CT: compute tomographic scan; D/C: discontinued; EOT: end of treatment; ESR:
erythrocyte sedimentation rate; G-CSF: granulocyte—-colony- stimulating factor; GM-CSF: granulocyte-macrophage—-colony-stimulating factor; GVHD: graft vs. host disease; IFN-? interferon-gamma; L-AMB:
liposomal amphotericin B; mo: month; wk: week; qod: every other day; TD: total dose.
202CANCER July 1, 2005 / Volume 104 / Number 1
matory cytokines (IFN-? and GM-CSF) might exacer-
During cytokine therapy, all patients were in com-
plete disease remission, and had normal neutrophil
counts for ? 1 month, no reduction in immunosup-
pressive therapy, and no addition of antifungal agents.
Thus, response of their fungal infection was not asso-
ciated with any of these parameters. In addition, the
three patients who underwent subsequent immuno-
suppression remained free of fungal infection at last
follow-up. Furthermore, the earlier response (within 7
days of initiation of cytokine therapy) observed in the
2 patients who exhibited findings compatible with a
strong inflammatory reaction (Patients 3 and 4) may
suggest a contribution of cytokines to the control of
Our findings support the favorable results ob-
served in case reports of refractory IFI (Table 2). These
reports described combination therapy with antifun-
gal agents and either IFN-?2–8or GM-CSF,9given to
four patients with chronic granulomatous disease
(CGD),2–4,7three patients with acute leukemia,5,6,9and
an otherwise healthy patient.8Our results differ from
previous reports in that antifungal treatment was dis-
continued in two patients, thus permitting the evalu-
ation of the relative contribution of cytokine therapy
alone to response and the use of a combination of
IFN-? plus a CSF.
Acute leukemias and their treatments can impair
the function and number of phagocytic and nonph-
agocytic cells directly or through the modulation of
cytokine production.1,10Neutrophils, monocytes, T
cells, and macrophages are critical for the suppression
and killing of Aspergillus spp. and Candida spp. IFN-?
enhances the function of both neutrophils and mono-
cytes against fungi, increases the hyphal damage me-
diated by phagocytes against several fungi, and shifts
the cellular-mediated immune response from a Th2 to
a Th1 pattern.1This cytokine has also been shown to
enhance the ability of neutrophils to damage Aspergil-
lus hyphae ex vivo in patients with CGD,11and to
accelerate the sterilization of the cerebrospinal fluid in
human immunodeficiency virus (HIV)-infected pa-
tients with cryptococcal meningitis.12Two of our pa-
tients (Patients 3 and 4) had worsening of the imaging
studies (liver, kidneys, or spleen) and 1 of these 2
developed lymphadenitis while clinically improving.
IFN-? has been shown to be crucial for the develop-
ment of granulomas13in animal models. It is possible
that these patients were unable to mount an adequate
inflammatory response because of severe immuno-
suppression, and that immune reconstitution with cy-
tokines allowed the formation of granulomas that
could then be more clearly delineated on imaging
studies. This phenomenon might be similar to that
observed in HIV-infected patients receiving highly ac-
tive antiretroviral therapy (HAART). In these patients,
subclinical infections may be unmasked by the en-
hancement of their immune system with HAART.14
The CSFs have also been shown to enhance the in
vitro antifungal activities of phagocytes against oppor-
tunistic fungi.1An in vitro additive antifungal effect
was also observed with the combination of IFN-? and
G-CSF and the combination of any of these cytokines
with antifungal agents.15
Our study is limited by the small cohort of pa-
tients, its retrospective nature, and the lack of sup-
porting laboratory studies. It could also be argued that
the favorable outcome was due to the concomitant
antifungal agent. This is unlikely, given the discontin-
uation of antifungal therapy in two patients and the
continuation of the same agents in the other two
patients who had progressive infection. In addition,
persistent infection before commencing cytokine
therapy was well documented in all patients, despite
prolonged antifungal therapy and recovery from neu-
We conclude that our pilot study suggests a po-
tential role for immunomodulation in patients with
cancer with refractory IFI. Based on our study, we
cannot recommend any specific timing for the initia-
tion of cytokine therapy but rather suggest this mo-
dality when there is clear evidence of failure to re-
spond to appropriate antifungal agents in a patient
with adequate neutrophil counts and remission of
1.Rodriguez-Adrian LJ, Grazziutti ML, Rex JH, Anaissie EJ. The
potential role of cytokine therapy for fungal infections in
patients with cancer: is recovery from neutropenia all that is
needed? Clin Infect Dis. 1998;26:1270–1278.
2.Bernhisel-Broadbent J, Camargo EE, Jaffe HS, Lederman
HM. Recombinant human interferon-gamma as adjunct
therapy for Aspergillus infection in a patient with chronic
granulomatous disease. J Infect Dis. 1991;163:908–911.
3.Phillips P, Forbes JC, Speert DP. Disseminated infection
with Pseudallescheria boydii in a patient with chronic gran-
ulomatous disease: response to gamma-interferon plus an-
tifungal chemotherapy. Pediatr Infect Dis J. 1991;10:536–
4.Pasic S, Abinun M, Pistignjat B, et al. Aspergillus osteomy-
elitis in chronic granulomatous disease: treatment with re-
combinant gamma-interferon and itraconazole. Pediatr In-
fect Dis J. 1996;15:833–834.
5.DeMaio J, Colman L. The use of adjuvant interferon-gamma
therapy for hepatosplenic Blastoschizomyces capitatus in-
fection in a patient with leukemia. Clin Infect Dis. 2000;31:
IFN-? and CSF for Fungal Infections/Dignani et al. 203
6. Bonig H, Korholz D, Lex C, Wolfel S, Gobel U. Monocyte Download full-text
deactivation and its reversal in a patient with chemothera-
py-induced leukopenia and severe systemic infection. Med
Pediatr Oncol. 2000;34:39–42.
Touza Rey F, Martinez Vazquez C, Alonso Alonso J, Mendez
Pineiro MJ, Rubianes Gonzalez M, Crespo Casal M. [The
clinical response to interferon-gamma in a patient with
chronic granulomatous disease and brain abscesses due to
Aspergillus fumigatus]. An Med Intern. 2000;17:86–87.
Kuberski TT, Servi RJ, Rubin PJ. Successful treatment of a
critically ill patient with disseminated coccidioidomycosis,
using adjunctive interferon-gamma. Clin Infect Dis. 2004;38:
Pagano L, Morace G, Ortu-La Barbera E, Sanguinetti M,
Leone G. Adjuvant therapy with rhGM-CSF for the treat-
ment of Blastoschizomyces capitatus systemic infection in a
patient with acute myeloid leukemia. Ann Hematol. 1996;
10. Hebart H, Bollinger C, Fisch P, et al. Analysis of T-cell
responses to Aspergillus fumigatus antigens in healthy indi-
viduals and patients with hematologic malignancies. Blood.
11. Rex JH, Bennett JE, Gallin JI, Malech HL, DeCarlo ES,
Melnick DA. In vivo interferon-gamma therapy augments
the in vitro ability of chronic granulomatous disease neu-
trophils to damage Aspergillus hyphae. J Infect Dis. 1991;163:
12. Pappas PG, Bustamante B, Ticona E, et al. Recombinant
Interferon-g1b as adjunctive therapy for AIDS-related acute
cryptococcal meningitis. J Infect Dis. 2004;189:2185–2191.
13. Yimin, Kohanawa M, Sato Y, Minagawa T. Role of T cells in
granuloma formation induced by Rhodococcus aurantiacus
is independent of their interferon-gamma production. J Med
14. Phillips P, Kwiatkowski MB, Copland M, Craib K, Montaner
J. Mycobacterial lymphadenitis associated with the initia-
tion of combination antiretroviral therapy. J Acquir Immune
Defic Syndr. 1999;20:122–128.
15. Stevens DA. Combination immunotherapy and antifungal
chemotherapy. Clin Infect Dis. 1998;26:1266–1269.
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