Immunotherapy for Infectious Diseases

Fungal Infections 307
rapid bone marrow recovery and shortened the duration of chemotherapy-associated
neutropenia. Second, highly effective antibiotics were introduced that reduced the incidence
and mortality of serious bacterial infections in neutropenic hosts. Third, a variety
of problems were associated with granulocyte transfusions, including concerns
about transmission of viral infection, toxic reactions, and alloimmunization. Fourth, the
logistics of collecting leukocytes and separating granulocytes were complex and often
resulted in inadequate numbers of cells for granulocyte transfusions.
In the past decade, interest in granulocyte transfusions was rekindled by several factors.
Granulocyte (G)-CSF was found to be useful in mobilizing large numbers of PMNs
from donors with normal antimicrobial function (12). In addition to increasing quantity,
G-CSF administration to donors also activates PMNs and produces a qualitative improvement
in their antimicrobial efficacy. Furthermore, G-CSF and interferon-� (IFN-�) can
be used to preserve leukocyte function after isolation from donors, irradiation, and storage
(13). The availability of G-CSF provided a solution to the problems of PMN quantity
and quality that were serious obstacles for granulocyte transfusion therapy in the past.
Another factor stimulating interest in granulocyte transfusion was the realization that
antimicrobial chemotherapy was not sufficient to treat infections in some neutropenic
patients. The increasing prevalence of antimicrobial-resistant organisms diminished the
efficacy of many empiric antibiotic regimens in patients with prolonged neutropenia. The
fact that some infections do not respond to antimicrobial therapy unless PMNs are present
has led several authorities to propose wider use of granulocyte transfusions (10).
However, many questions remain regarding the appropriate use of granulocyte transfusions,
including the selection of patients, the quality and safety of G-CSF-stimulated
leukocytes, the indications for therapy, and the cost benefit of this intervention (10,14).
The effectiveness of granulocyte transfusions against invasive fungal infections may
be lower than that against bacterial infections (10). At this time, there are not sufficient
data to recommend routine granulocyte transfusions for neutropenic patients with invasive
fungal infections (10). Nevertheless, several reports suggest that granulocyte transfusions
can be useful for the therapy of some types of fungal infection in patients with
prolonged neutropenia (15–18). Fusarium infections in neutropenic patients respond
poorly to antifungal therapy, and resolution usually requires recovery of bone marrow
function (16). Some patients with Fusarium infection and neutropenia have responded
favorably to CSF-elicited granulocyte transfusions, and it has been suggested that this
modality can “buy time” until recovery from myelosuppression (16). There is one
report of a successful therapy of disseminated Fusarium infection using a combination
of amphotericin B, granulocyte/macrophage (GM)-CSF, and granulocyte transfusions
(see Table 4). A man with invasive Aspergillus sinusitis was successfully managed
with amphotericin B colloidal dispersion and granulocyte transfusions from G-CSFstimulated
donors during the neutropenic period following bone marrow transplant
(17). Another man with disseminated Aspergillus infection in the setting of aplastic
anemia was cured by combination therapy with amphotericin B, itraconazole, granulocyte
transfusions from G-CSF-stimulated donors, GM-CSF, and G-CSF (19). An
8-year-old boy with chronic granulomatous disease and Aspergillus infection was cured
by bone marrow transplantation, CSF-mobilized granulocyte transfusions, and amphotericin
B (20). Two individuals with Candida tropicalis fungemia following bone marrow
transplantation were cured by combination-therapy amphotericin B and granulocyte