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The safety of interferon‐γ‐1b therapy for invasive fungal infections after hematopoietic stem cell transplantation
Author(s) -
Safdar Amar,
Rodriguez Gilhen,
Ohmagari Norio,
Kontoyiannis Dimitrios P.,
Rolston Kenneth V.,
Raad Issam I.,
Champlin Richard E.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20883
Subject(s) - medicine , hematopoietic stem cell transplantation , stem cell , transplantation , haematopoiesis , hematopoietic stem cell , interferon , hematopoietic cell , immunology , biology , genetics
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‐γ‐1b as an immune‐modulatory therapy HSCT recipients. METHODS Thirty‐two patients received interferon‐γ‐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‐γ‐1b and antifungals to treat infections; the other patients received interferon‐γ‐1b to promote autologous graft‐versus‐tumor effect. Interferon‐γ‐1b usually was administered at a dose of 50 μg subcutaneously every other day. The median duration (± standard deviation) of interferon‐γ‐1b therapy was 6 ± 6.5 doses (range, 1–29 doses), and the median cumulative dose was 487 ± 453 μg (range, 35–2175 μg). During therapy with interferon‐γ‐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— γ‐1b‐related episodes of neutropenia, thrombocytopenia, anemia, or liver dysfunction. Interferon‐γ‐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‐γ‐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‐γ‐1b. CONCLUSIONS Recombinant interferon‐γ‐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. Cancer 2005. © 2005 American Cancer Society.