Recombinant interferon gamma1b 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 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.
Safdar
Amar
A
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
Rodriguez
Gilhen H
GH
Lichtiger
Benjamin
B
Dickey
Burton F
BF
Kontoyiannis
Dimitrios P
DP
Freireich
Emil J
EJ
Shpall
Elizabeth J
EJ
Raad
Issam I
II
Kantarjian
Hagop M
HM
Champlin
Richard E
RE
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
D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents; D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma