The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation.
BACKGROUND
The restoration of normal immune responses, especially of the T-helper type 1 immune response, is an important predictor of fungal infection outcome in patients with malignant disease who undergo hematopoietic stem cell transplantation (HSCT). The authors sought to evaluate the safety of adjuvant recombinant interferon-gamma-1b as an immune-modulatory therapy HSCT recipients.


METHODS
Thirty-two patients received interferon-gamma-1b after undergoing HSCT at the author's institution between 1998 and 2003. A retrospective analysis was undertaken after obtaining permission from the Institutional Review Board.


RESULTS
Twenty-six of 32 patients (81%) received allogeneic stem cell grafts. All but 1 patient received interferon-gamma-1b and antifungals to treat infections; the other patients received interferon-gamma-1b to promote autologous graft-versus-tumor effect. Interferon-gamma-1b usually was administered at a dose of 50 mug subcutaneously every other day. The median duration (+/- standard deviation) of interferon-gamma-1b therapy was 6+/-6.5 doses (range, 1-29 doses), and the median cumulative dose was 487+/-453 mug (range, 35-2175 microg). During therapy with interferon-gamma-1b, fever was common (n=9 patients; 28%). In 1 patient (3%), new-onset lymphocytopenia occurred but resolved after cytokine therapy was discontinued; there were no interferon- gamma-1b-related episodes of neutropenia, thrombocytopenia, anemia, or liver dysfunction. Interferon-gamma-1b therapy did not precipitate or exacerbate acute or chronic graft-versus-host disease (GVHD). In fact, in 2 of 7 patients (29%) with acute GVHD and in 3 of 10 patients (30%) with chronic GVHD, significant improvements in GVHD were noted during therapy with interferon-gamma-1b. Among the 26 patients with aspergillosis, 14 patients (54%) died. However, 5 of 10 patients (50%) with presumed pulmonary aspergillosis, 3 of 9 patients (33%) with probable pulmonary aspergillosis, 1 of 2 patients (50%) with definite pulmonary aspergillosis, and 3 of 5 patients (60%) with disseminated aspergillosis responded to antifungals and adjuvant interferon-gamma-1b.


CONCLUSIONS
Recombinant interferon-gamma-1b was tolerated without serious adverse reactions in HSCT recipients. A large, prospective, randomized study will be needed to evaluate the efficacy of this cytokine in high-risk HSCT recipients who have invasive mycoses.
Safdar
Amar
A
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. asafdar@mdanderson.org
Rodriguez
Gilhen
G
Ohmagari
Norio
N
Kontoyiannis
Dimitrios P
DP
Rolston
Kenneth V
KV
Raad
Issam I
II
Champlin
Richard E
RE
D000935:Antifungal Agents / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009369:Neoplasms / Q000628:therapy; D011994:Recombinant Proteins; D012189:Retrospective Studies
D000935:Antifungal Agents; D011994:Recombinant Proteins; D007371:Interferon-gamma