Neutrophil and platelet-related parameters in sublethally γ-irradiated (700 cGy) or x-irradiated (600 cGy) rhesus monkeys treated with myelopoietin: duration, nadir, time to recovery, and clinical support
| Neutrophil-Related Parameters . | ||||
|---|---|---|---|---|
| Treatment . | Duration (days) Neutropenia . | ANC Nadir (μL−1) . | Time to Recovery (days) . | Antibiotics Required (days) . |
| Series 1 (700 cGy) | ||||
| HSA | 14.8 ± 0.7 | 0 | 19.7 ± 0.5 | 17.4 ± 1.1 |
| MPO, BID (200 μg/kg) | 7.3 ± 3.13-150,3-151 | 390 ± 553-151,3-152 | 12.3 ± 3.13-151 | 7.5 ± 3.33-151 |
| MPO, BID (50 μg/kg)3-153 | 12.0 | 36 | 15.5 | 12.5 |
| Previous data set (700 cGy) | ||||
| HSA | 14.8 ± 0.7 | 0 | 19.7 ± 0.5 | 17.4 ± 1.1 |
| Daniplestim alone, BID | 14.1 ± 1.8 | 92 ± 3.03-151,3-155 | 19.8 ± 0.93-155 | 13.4 ± 1.83-150 |
| G-CSF alone, QD | 12.4 ± 0.53-150 | 5 ± 4 | 16.2 ± 0.63-151 | 13.8 ± 0.63-151 |
| Daniplestim, BID/G-CSF, QD | 10.6 ± 0.73-151 | 124 ± 473-151,3-155 | 15.0 ± 0.63-151,3-155 | 9.2 ± 1.73-151,3-155 |
| Series 2 (600 cGy) | ||||
| 0.1% AS-control | 16.2 ± 0.4 | 8 ± 4 | 21.7 ± 0.4 | 19.3 ± 0.5 |
| MPO, QD | 7.2 ± 2.03-151 | 377 ± 423-151,3-152 | 9.2 ± 3.83-151,3-152 | 10.0 ± 1.93-151 |
| Platelet-related parameters | ||||
| Treatment | Duration (d) Thrombocytopenia | PLT Nadir (μL−1) | Time to Recovery (d) | Transfusions |
| Series 1 (700 cGy) | ||||
| HSA | 11.9 ± 1.6 | 5,000 ± 600 | 20.7 ± 1.4 | 1.7 ± 0.5 |
| MPO (200 μg/kg) | 2.0 ± 1.23-151 | 35,000 ± 10,0003-151 | 7.5 ± 3.33-151 | 1.0 ± 0.7 |
| MPO (50 μg/kg)3-153 | 6.0 | 10,000 | 15.5 | 2.0 |
| Previous data set (700 cGy) | ||||
| HSA | 11.9 ± 1.6 | 5,000 ± 600 | 20.7 ± 1.4 | 1.7 ± 0.5 |
| Daniplestim alone, BID | 3.5 ± 1.23-151,3-155 | 14,400 ± 3,0003-151,3-155 | 13.2 ± 3.33-150 | 0.4 ± 0.23-150 |
| G-CSF alone, QD | 7.2 ± 0.93-150 | 7,400 ± 2,0003-150 | 16.4 ± 0.73-150 | 1.4 ± 0.8 |
| Daniplestim, BID/G-CSF, QD | 1.9 ± 0.83-151,3-155 | 22,200 ± 5,3003-151,3-155 | 8.6 ± 3.53-151,3-155 | 0 ± 03-151 |
| Series 2 (600 cGy) | ||||
| 0.1% AS-control | 10.4 ± 0.8 | 3,000 ± 1,000 | 20.7 ± 0.9 | 2.6 ± 0.4 |
| MPO, QD | 3.2 ± 1.03-151 | 28,000 ± 10,4003-151 | 11.8 ± 2.23-151 | 0 ± 03-151 |
| Neutrophil-Related Parameters . | ||||
|---|---|---|---|---|
| Treatment . | Duration (days) Neutropenia . | ANC Nadir (μL−1) . | Time to Recovery (days) . | Antibiotics Required (days) . |
| Series 1 (700 cGy) | ||||
| HSA | 14.8 ± 0.7 | 0 | 19.7 ± 0.5 | 17.4 ± 1.1 |
| MPO, BID (200 μg/kg) | 7.3 ± 3.13-150,3-151 | 390 ± 553-151,3-152 | 12.3 ± 3.13-151 | 7.5 ± 3.33-151 |
| MPO, BID (50 μg/kg)3-153 | 12.0 | 36 | 15.5 | 12.5 |
| Previous data set (700 cGy) | ||||
| HSA | 14.8 ± 0.7 | 0 | 19.7 ± 0.5 | 17.4 ± 1.1 |
| Daniplestim alone, BID | 14.1 ± 1.8 | 92 ± 3.03-151,3-155 | 19.8 ± 0.93-155 | 13.4 ± 1.83-150 |
| G-CSF alone, QD | 12.4 ± 0.53-150 | 5 ± 4 | 16.2 ± 0.63-151 | 13.8 ± 0.63-151 |
| Daniplestim, BID/G-CSF, QD | 10.6 ± 0.73-151 | 124 ± 473-151,3-155 | 15.0 ± 0.63-151,3-155 | 9.2 ± 1.73-151,3-155 |
| Series 2 (600 cGy) | ||||
| 0.1% AS-control | 16.2 ± 0.4 | 8 ± 4 | 21.7 ± 0.4 | 19.3 ± 0.5 |
| MPO, QD | 7.2 ± 2.03-151 | 377 ± 423-151,3-152 | 9.2 ± 3.83-151,3-152 | 10.0 ± 1.93-151 |
| Platelet-related parameters | ||||
| Treatment | Duration (d) Thrombocytopenia | PLT Nadir (μL−1) | Time to Recovery (d) | Transfusions |
| Series 1 (700 cGy) | ||||
| HSA | 11.9 ± 1.6 | 5,000 ± 600 | 20.7 ± 1.4 | 1.7 ± 0.5 |
| MPO (200 μg/kg) | 2.0 ± 1.23-151 | 35,000 ± 10,0003-151 | 7.5 ± 3.33-151 | 1.0 ± 0.7 |
| MPO (50 μg/kg)3-153 | 6.0 | 10,000 | 15.5 | 2.0 |
| Previous data set (700 cGy) | ||||
| HSA | 11.9 ± 1.6 | 5,000 ± 600 | 20.7 ± 1.4 | 1.7 ± 0.5 |
| Daniplestim alone, BID | 3.5 ± 1.23-151,3-155 | 14,400 ± 3,0003-151,3-155 | 13.2 ± 3.33-150 | 0.4 ± 0.23-150 |
| G-CSF alone, QD | 7.2 ± 0.93-150 | 7,400 ± 2,0003-150 | 16.4 ± 0.73-150 | 1.4 ± 0.8 |
| Daniplestim, BID/G-CSF, QD | 1.9 ± 0.83-151,3-155 | 22,200 ± 5,3003-151,3-155 | 8.6 ± 3.53-151,3-155 | 0 ± 03-151 |
| Series 2 (600 cGy) | ||||
| 0.1% AS-control | 10.4 ± 0.8 | 3,000 ± 1,000 | 20.7 ± 0.9 | 2.6 ± 0.4 |
| MPO, QD | 3.2 ± 1.03-151 | 28,000 ± 10,4003-151 | 11.8 ± 2.23-151 | 0 ± 03-151 |
Series 1. Monkeys were total body irradiated (TBI) to 700 cGy with60Co-γ-radiation and treated with control protein, HSA (n = 10) or MPO at 200 μg/kg/d (n = 4) or 50 μg/kg/d (n = 2), BID, according to protocol (Methods). Data represents mean values ± SEM.
Series 2. Monkeys were total body irradiated (TBI) to 600 cGy with x-radiation and treated with control protein, autologous serum (AS) (n = 11) or MPO at 200 μg/kg/d, QD, (n = 5) according to protocol (Methods). Data represents mean values ± SEM.
Previous Data Set. Published study showing effects of coadministered daniplestim (BID) plus G-CSF (QD) relative to daniplestim and G-CSF monotherapy in the same 700 cGy 60Co-γ-radiation animal model performed in the same approximate time frame as Series 1.33 The control cohort (n = 10) is the same as series 1. The duration of neutropenia is defined as days of ANC <500/μL and thrombocytopenia is defined as days of platelets <20,000/μL. Time to recovery is the number of days required for the ANC to reach ≥500/μL and platelets to reach ≥20,000/μL.
Statistically different from HSA/AS-treated controls (P ≤ .05).
Statistically different from HSA/AS-treated controls (P ≤ .01).
Statistically different from daniplestim(BID)/G-CSF(QD) treated animals (P ≤ .02).
Values for MPO treated with 50 μg/kg/d were not evaluated statistically at n = 2.
Statistically different from G-CSF-treated animals (P ≤ .05).