Combination Therapy for Radiation-Induced Bone Marrow Aplasia in Nonhuman Primates Using Synthokine SC-55494 and Recombinant Human Granulocyte Colony-Stimulating Factor
Abstract
Combination cytokine therapy continues to be evaluated in an effort to stimulate multilineage hematopoietic reconstitu- tion after bone marrow myelosuppression. This study evalu- ated the efficacy of combination therapy with the synthetic interleukin-3 receptor agonist, Synthokine-SC55494, and recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF) on platelet and neutrophil recovery in nonhuman primates exposed to total body 700 cGy 60Co gamma radiation. After irradiation on day (d) 0, cohorts of animals subcutaneously received single-agent protocols of either human serum albumin (HSA; every day [OD], 15 microng/kg/d. n = 10). Synthokine (twice daily [BID], 100 microng/kg/d, n = 5), rhG-CSF (QD, 10 microng/kg/d, n = 5). or a combination of Synthokine and rhG-CSF (BID, 100 and 10 microng/kg/d, respectively, n = 5) for 23 days beginning on dl. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (absolute neutrophil count <500/micronLiter) and thrombocytopenia (platelet count <20,00O/micronLiter) were assessed. Animals were provided clinical support in the form of antibiotics, fresh irradiated whole blood, and fluids. All cytokine protocols significantly (P < .05) reduced the duration of thrombocytopenia versus the HSA-treated animals. Only the combination protocol of Synthokine + rhG-CSF and rhG-CSF alone significantly shortened the period of neutropenia (P < .05). The combined SynthokinelrhG-CSF protocol significantly improved platelet nadir versus Synthokine alone and HSA controls and neutrophil nadir versus rhG-CSF alone and HSA controls. All cytokine protocols decreased the time to recovery to preirradiation neutrophil and platelet values. The SynthokinelrhG-CSF protocol also reduced the transfusion requirements per treatment group to 0 among 5 animals as compared with 2 among 5 animalsfor Synthokine alone, 8 among 5 animals for rhG-CSF, and 17 among 10 animals for HSA.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 15, 1996
- Accession Number
- ADA475660
Entities
People
- Ann M. Farese
- Charles M. Baum
- Francis Herodin
- John P. Mckearn
- Lisa B. Grab
- Thomas J. Macvittle
Organizations
- Armed Forces Radiobiology Research Institute