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

Abstract

BACKGROUNDThe 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 γ1b (rIFN‐γ1b) in patients with cancer who received GTX for refractory, systemic, opportunistic infections.METHODSTwenty recipients of high‐dose donor GTX (≈5.5 × 1010 neutrophils per transfusion) who had received concurrent rIFN‐γ1b between October 2001 and December 2004 were evaluated retrospectively.RESULTSThe 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‐γ1b 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‐γ1b therapy. Patients received a median ± SD of 8 ± 7 GTX doses (range, 4‐28 doses) and 9 ± 7 rIFN‐γ1b doses (range, 1‐28 doses), for a mean ± SD cumulative dose (CD) of 400 ± 2621 μg. Other concomitant cytokines were granulocyte‐colony stimulating factor (12 ± 3 doses; CD, 6720 ± 4721 μg) in 15 patients (75%) and granulocyte‐macrophage–colony stimulating factor (12 ± 9 doses; CD, 4750 ± 4410 μg) 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‐γ1b‐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.CONCLUSIONSThe current results indicated that no serious adverse events were associated with rIFN‐γ1b immune enhancement in patients with systemic opportunistic infections who received donor GTX therapy. Cancer 2006. © 2006 American Cancer Society.

Human herpesvirus-6 DNAemia in immunosuppressed adult patients with leukemia at risk for mold infection

“…Granulocyte transfusions have been more widely used in recent years as adjuvant therapy. 5 We found that more than one third of the patients with HHV-6 DNAemia had received such transfusions.…”

Human NK Cells Display Important Antifungal Activity againstAspergillus fumigatus, Which Is Directly Mediated by IFN-γ Release

“…In a similar animal model, it was shown that NK cell-derived IFN-g was the protective factor against IA (8,9). Clinical data confirmed an antifungal and, more specifically, the anti-Aspergillus activity of IFN-g (7,(10)(11)(12)(13)(14). These studies attributed the beneficial effect of IFN-g to its immunoregulatory role with phagocytes of the innate immune system, which are conventionally involved in the host defense against A. fumigatus (11,15).…”

Randomized phase III study of granulocyte transfusions in neutropenic patients

“…Additionally, there was no difference in the neutrophil response to the first or subsequent GT in any single recipient, suggesting that antineutrophil immunization of the recipient did not occur or was not clinically relevant. Concomitant cytokine therapy in addition to G-CSF to enhance the function of transfused neutrophils, such as recombinant IFN-g1b, has shown promising results, [20][21][22] but detection or pharmacological stimulation of neutrophil function were not part of this study, which relied on neutrophil counts and clinical performance parameters. Peripheral blood counts might be an inadequate surrogate marker to assess the efficacy of GT because neutrophil tissue infiltration at the site of infection precedes the peripheral blood ANC increment.…”