The role of granulocyte transfusion and colony stimulating growth factors as adjuvant treatment of fungal infection

Ref ID: 19466

Author:

L. Pagano

Author address:

Catholic University, Roma, Italy

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Various situations can induce neutropenia, in particular malignan-
cies, radiation therapy, autoimmune diseases, HIV and above all
hematological malignancies. In particular among hematological
patients those affected by acute myeloid leukemia must to be consid-
ered at highest risk for invasive fungal infection (IFI). In fact these
patients underwent to a deep neutropenia secondary to the use of
myeloablative treatments for the underlying hematological malig-
nancy (HM).
The role of neutrophils is basic in the control of fungal infections
being essential in initiation and execution of the acute inflammatory
response and subsequent resolution of fungal infection. Usually neu-
trophils, with macrophages, internalize resting or swollen conidia
and use mechanisms such as respiratory burst to combat IFI. It is
well known that longer and deep is the neutropenia and higher is
the incidence of serious infections including IFI.
In fact all the clinical series on IFI reported in literature, collecting
a relevant number of patients with HM, showed that this infection
onset in patients with a prolonged neutropenia: the percentage of
patients that developed IFI while neutropenic, ranges from 60% to
90%, with a median duration of neutropenia ranging from 12 to
16 days.
Neutropenia does not influence only the onset of the fungal com-
plication but also the outcome. In all the reported series, the recovery
from neutropenia is statistically correlated with the improvement of
the infection.
The action of neutrophils against fungi was based on two major
points, firstly with a direct attack to fungi causing a lesion of the
fungal vessel and subsequently destruction by macrophages; in the
second important role the neutrophils could enhance the activity of
antifungal drugs.
To overcome the neutropenia during these infections it has been
suggested the use of colony stimulating growth factors or the use of
granulocyte transfusions (GTX).
The main colony stimulating growth factors tested in patients with
fungal infection are. macrophage colony stimulating factor (M-CSF),
granulocyte macrophage colony stimulating factor (GM-CSF) and
granulocyte colony stimulating factor (G-CSF).
Regarding M-CSF and GM-CSF data are very poor and their utiliza-
tion, although preliminary results were really interesting, is greatly
reduced, also because, as in the case of M-CSF, there was not a
development from the Industries. The G-CSF is the growth factor cur-
rently most used, but the advantage of its use in fungal infections is
questionable. Meta-analysis studies have not demonstrated its useful-
ness and also in various clinical series of patients with aspergillosis
using the G-CSF did not modify the outcome of the patients. A
hypothesis is that the use of G-CSF induces the production of young
neutrophils not able to destroy very complex microbes as fungi.
The transfusion of granulocytes (GTX) to neutropenic recipients
represents a logical approach to overcome the deficiency of neutroph-
ils and is indicated above all in patients with fungal infections.
A recent Cochrane metanalysis on the use of GTX in neutropenic
patients showed an advantage in overall mortality, duration of febrile
days and recovery of bacterial infections, however data on patients
with IFI are scanty. While Sadfar et al, (Cancer 2004) showed a sig-
nificant advantage with GTX administration during candidemia
comparing 29 patients treated with GTX to 462 not treated, regard-
ing molds infections (aspergillosis and mucormycosis) only very small
series and case reports are present and are not conclusive.
In conclusion neutropenia represents the major predisposing factor
for IFI not only in hematological malignancies but also in other cate-
gories of patients. The improvement in clinical manifestations is closely
related to neutrophils recovery. Strategies aiming to increase neu-
trophils count and function (G-CSF and GTX) play an important role in
the management of these life-threatening infectious complications.

Abstract Number: w16.2

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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