Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions

Cancer. 2006 Jun 15;106(12):2664-71. doi: 10.1002/cncr.21929.

Abstract

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 gamma1b (rIFN-gamma1b) in patients with cancer who received GTX for refractory, systemic, opportunistic infections.

Methods: Twenty recipients of high-dose donor GTX ( approximately 5.5 x 10(10) neutrophils per transfusion) who had received concurrent rIFN-gamma1b 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-gamma1b 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-gamma1b therapy. Patients received a median +/- SD of 8 +/- 7 GTX doses (range, 4-28 doses) and 9 +/- 7 rIFN-gamma1b doses (range, 1-28 doses), for a mean +/- SD cumulative dose (CD) of 400 +/- 2621 microg. Other concomitant cytokines were granulocyte-colony stimulating factor (12 +/- 3 doses; CD, 6720 +/- 4721 microg) in 15 patients (75%) and granulocyte-macrophage-colony stimulating factor (12 +/- 9 doses; CD, 4750 +/- 4410 microg) 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-gamma1b-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-gamma1b immune enhancement in patients with systemic opportunistic infections who received donor GTX therapy.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Antifungal Agents / adverse effects
  • Antifungal Agents / immunology*
  • Antifungal Agents / therapeutic use*
  • Child
  • Combined Modality Therapy
  • Cytokines / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Drug Therapy, Combination
  • Female
  • Gram-Negative Bacterial Infections / complications
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / mortality
  • Granulocytes / transplantation*
  • Hematologic Neoplasms / complications*
  • Hematologic Neoplasms / therapy
  • Humans
  • Interferon-gamma / adverse effects
  • Interferon-gamma / immunology*
  • Interferon-gamma / therapeutic use*
  • Leukocyte Transfusion*
  • Male
  • Middle Aged
  • Mycoses / complications
  • Mycoses / drug therapy*
  • Mycoses / mortality
  • Neutropenia / etiology
  • Opportunistic Infections / complications
  • Opportunistic Infections / drug therapy*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antifungal Agents
  • Cytokines
  • Recombinant Proteins
  • Interferon-gamma