title: Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions.
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.
authors.affiliation: 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
authors.forename: Amar
authors.initials: A
authors.lastname: Safdar
authors.forename: Gilhen H
authors.initials: GH
authors.lastname: Rodriguez
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lichtiger
authors.forename: Burton F
authors.initials: BF
authors.lastname: Dickey
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Issam I
authors.initials: II
authors.lastname: Raad
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D002648:Child; D003131:Combined Modality Therapy; D016207:Cytokines / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D006098:Granulocytes / Q000637:transplantation*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D017708:Leukocyte Transfusion; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000209:etiology; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents; D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma