Immunomodulation by IFN-gamma in patients with resistant infections and accompanying Bronchiolitis obliterans following allogeneic stem cell transplantation – 64257; rst experience in heavily pre-treated patients

Ref ID: 18581

Author:

J. Ammer, K. Landfried, A. Hautmann, B. Holler, D. Wolff,
G. Hildebrandt, J. Hahn, R. Andreesen, E. Holler
Internal Medicine I

Author address:

(Regensburg, DE)

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Objective: Fungal infections such as aspergillosis and severe
graft-versus-host disease (GvHD) affecting the lung, especially bronchiolitis obliterans (BO), are the most serious long
term complications following allogeneic stem cell transplantation (SCT). Furthermore, patients suffering from BO frequently
present with fungal superinfections. Recently, IFN-gamma has
been suggested as an additive treatment in haematological
patients with infections resistant to conventional antimycotic
treatment. In addition, our group has reported heterozygous
NOD2/CARD15 single nucleotide polymorphisms (SNPs) indicating a diminished antimicrobial defense as risk factors of
BO. As IFN-gamma has been shown to strongly induce NOD2/
CARD15 expression, we speculated that immunomodulation
by IFN-gamma might improve antimicrobial defense in patients
suffering from BO.
Methods: In a pilot series, 5 patients received a total of
7 courses of subcutaneous injections of IFN-gamma 3 times a
week for an average of 182 weeks. Indications were resistant
invasive aspergillosis (4 pulmonary, 1 with concomitant BO, 1
sinuses), atypical mycobacterial infection in a patient with BO
and therapy resistant and ventilator dependent BO with bacterial superinfection in another patient.
Results: Pulmonary aspergillosis and infections improved clinically and by CT scan in all patients. CT signs of BO improved in 2
of 3 patients with BO and were stable in the 3rd patient. Impressively, the ventilator dependent patient could be wheaned with
marked improvement of hypercapnia and another BO patient
became oxygen-independent, whereas obstruction did not
change in pulmonary function tests. There were no negative
effects on extrapulmonary symptoms of acute or chronic GvHD.
Hematological side effects were tolerable although moderate
anemia might be induced.
Conclusion: Our preliminary results suggest that IFN-gamma
can be savely used to treat fungal infections resistant to antimycotic treatment in recipients of allogeneic SCT. In addition, IFNgamma might result in benefi cial immunomodulation restoring
homeostasis in epithelial GvHD as it is also suggested by recent
experimental data on allogeneic SCT in IFN-gamma knockout
mice. Further data and a prospective trial addressing this treatment option are needed.

Abstract Number: P746

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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