Recombinant interferon γ1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions

BACKGROUND. The response to antifungal therapy alone often is suboptimal in patients with cancer who have therapy-refractory neutropenia, and even donor-derived granulocyte transfusions (GTX) are not always successful. The authors evaluated the safety and efficacy of immune enhancement using recombinant interferon gamma 1b (rIFN-gamma 1b) in patients with cancer who received GTX for refractory, systemic, opportunistic infections. METHODS. Twenty recipients of high-dose donor GTX (approximate to 5.5 x 10(10) neutrophils per transfusion) who had received concurrent rIFN-gamma 1b between October 2001 and December 2004 were evaluated retrospectively. RESULTS. The median age (+/- standard deviation [SD]) was 45 +/- 17 years. Ten patients (50%) were men, 17 patients (85%) had leukemia, and 3 patients (15%) had myelodysplastic syndrome. The median +/- SD Acute Physiology and Chronic Health Evaluation II score was 15 +/- 4 (range, 7-22). Most patients (n = 18 patients; 90%) had recurrent or refractory cancer. In 6 patients (30%) who received allogeneic hematopoietic stem cell transplantation, GTX plus rIFN-gamma 1b was given a median +/- SD of 26 +/- 100 days (range, 12-372 days) after transplantation. Seventeen patients (85%) had neutropenia during GTX therapy. Five patients (25%) had possible invasive fungal infection, 3 patients (15%) had probable invasive fungal infection, and 11 patients (55%) had proven invasive fungal infection. One patient (5%) had refractory Pseudomonas aeruginosa sepsis. Eight patients (40%) received corticosteroids during GTX plus rIFN-gamma 1b therapy. Patients received a median +/- SD of 8 +/- 7 GTX doses (range, 4-28 doses) and 9 +/- 7 rIFN-gamma 1b doses (range, 1-28 doses), for a mean +/- SD cumulative dose (CD) of 400 +/- 2621 mu g. Other concomitant cytokines were granulocyte-colony stimulating factor (12 3 doses; CD, 6720 +/- 4721 mu g) in 15 patients (75%) and granulocyte-macrophage-colony stimulating factor (12 +/- 9 doses; CD, 4750 +/- 4410 mu g) in 14 patients (70%). Four patients (20%) developed fever, and 2 patients (10%) developed skin rashes. Reversible liver dysfunction (n = 3 patients; 15%) and tachycardia (n = 1 patients; 5%) were considered rIFN-gamma 1b-associated adverse reactions; whereas, in 1 patient (5%), transient dyspnea was attributed to GTX Four weeks after therapy started, 9 patients (45%) had complete or partial resolution of infection; and, in another 3 patients (15%), the invasive fungal infection had become stable. CONCLUSIONS. The current results indicated that no serious adverse events were associated with rIFN-gamma 1b immune enhancement in patients with systemic opportunistic infections who received donor GTX therapy.