Dogs Administered 9.2 Gy TBI, Hematopoietic Grafts From DLA-Nonidentical, Unrelated Donors, Followed by MMF With or Without CSP Treatment
| Dog No. . | Donor Cells Infused (×108/kg) . | Marrow Engraftment . | Marrow Cellularity (%) . | GVHD . | Survival (d) . | Weight Loss (%) . | Cause of Death . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Clinical . | Histological . | |||||||||
| Marrow . | Buffy Coat . | Acute . | Chronic . | |||||||
| Group 1 | ||||||||||
| D876 | 3.8 | 19.6 | Yes | 75-150 | S, G | NA | S, L, G | 20 | 28 | GVHD, ET1 |
| D935 | 1.5 | 12.8 | Yes | 100-150 | S, L, G | NA | S, L, G | 23 | 33 | GVHD, ET1 |
| D954 | 1.3 | 13.2 | No | 0 | — | NA | ;— | 8 | 25 | ET1 |
| D957 | 4.0 | 16.1 | Yes | 100-150 | S, G | NA | S, L, G | 28 | 33 | GVHD, ET1 |
| D958 | 3.5 | 9.1 | Yes | 35-150 | S, G | NA | S, L, G | 18 | 36 | Pneumonia |
| D972 | 2.9 | 13.1 | No | 0 | — | NA | ;— | 12 | 17 | Infection, GI bleeding |
| Group 2 | ||||||||||
| D868 | 4.0 | 13.2 | Yes | 10-150 | — | NA | ;— | 6 | 15 | MMF and CSP toxicities, ET1 |
| D910 | 3.6 | 9.8 | Yes | 60-150 | G | NA | S±, L±, G | 28 | 40 | Weight loss, ET1 |
| D911 | 2.8 | 11.7 | Yes | 100-150 | — | NA | S±, L±, G | 98 | 22 | Myocarditis |
| D936 | 2.1 | 16.5 | Yes | 5-150 | — | NA | ;— | 8 | 15 | MMF and CSP toxicities, ET1 |
| Group 3 | ||||||||||
| D823 | 4.1 | 15.2 | Yes | 100-150 | — | S | S, L, G± | 106 | 34 | Skin GVHD, ET1 |
| D960 | 3.3 | 12.6 | Yes | 100-150 | — | NA | S, L, G | 72 | 25 | Pneumonia and meningitis |
| D962 | 2.6 | 15 | Yes | 5-150 | — | NA | ;— | 7 | 17 | Intussusception, septicemia, ET1 |
| D967 | 3.7 | 10.3 | Yes | 100-150 | S, G | NA | S, L, G | 48 | 38 | Pneumonia, ET1 |
| D988 | 3.4 | 11.9 | Yes | 100-150 | — | — | (chronic) G | >540 | 30 | ET2 |
| D992 | 3.6 | 9.8 | Yes | 100-150 | — | — | S, L, (chronic) G± | >420 | 19 | ET2 |
| E071 | 3.8 | 11.2 | Yes | 100-150 | — | — | L, G± | >420 | 38 | ET2 |
| E072 | 4.0 | 13.6 | Yes | 100-150 | — | — | S±, L, (chronic) G± | >510 | 29 | ET2 |
| E223 | 3.7 | 15.8 | Yes | 100-150 | — | S± | S, L, (chronic) G | >420 | 26 | ET2 |
| Group 4 | ||||||||||
| E119 | 2.2 | 9.2 | Yes | 100-150 | — | — | S±, L, (chronic) G | >316 | 23 | ET2 |
| E168 | 2.7 | 8.8 | Yes | 100-150 | — | S | S, L | 119 | 18 | Skin GVHD, ET1 |
| E171 | 3.6 | 9.4 | Yes | 100-150 | — | S | S, L, G± | >224 | 8 | ET2 |
| E207 | 4.0 | 6.3 | Yes | 100-150 | — | S± | S, L, (chronic) G | >216 | 21 | ET2 |
| E210 | 4.1 | 17.1 | Yes | 100-150 | L | NA | S, L, (chronic) G | 95 | 41 | Infection, GVHD, renal failure |
| E211 | 3.5 | 15.5 | Yes | 100-150 | — | NA | S±, G | 38 | 25 | Meningitis, ET1 |
| Dog No. . | Donor Cells Infused (×108/kg) . | Marrow Engraftment . | Marrow Cellularity (%) . | GVHD . | Survival (d) . | Weight Loss (%) . | Cause of Death . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Clinical . | Histological . | |||||||||
| Marrow . | Buffy Coat . | Acute . | Chronic . | |||||||
| Group 1 | ||||||||||
| D876 | 3.8 | 19.6 | Yes | 75-150 | S, G | NA | S, L, G | 20 | 28 | GVHD, ET1 |
| D935 | 1.5 | 12.8 | Yes | 100-150 | S, L, G | NA | S, L, G | 23 | 33 | GVHD, ET1 |
| D954 | 1.3 | 13.2 | No | 0 | — | NA | ;— | 8 | 25 | ET1 |
| D957 | 4.0 | 16.1 | Yes | 100-150 | S, G | NA | S, L, G | 28 | 33 | GVHD, ET1 |
| D958 | 3.5 | 9.1 | Yes | 35-150 | S, G | NA | S, L, G | 18 | 36 | Pneumonia |
| D972 | 2.9 | 13.1 | No | 0 | — | NA | ;— | 12 | 17 | Infection, GI bleeding |
| Group 2 | ||||||||||
| D868 | 4.0 | 13.2 | Yes | 10-150 | — | NA | ;— | 6 | 15 | MMF and CSP toxicities, ET1 |
| D910 | 3.6 | 9.8 | Yes | 60-150 | G | NA | S±, L±, G | 28 | 40 | Weight loss, ET1 |
| D911 | 2.8 | 11.7 | Yes | 100-150 | — | NA | S±, L±, G | 98 | 22 | Myocarditis |
| D936 | 2.1 | 16.5 | Yes | 5-150 | — | NA | ;— | 8 | 15 | MMF and CSP toxicities, ET1 |
| Group 3 | ||||||||||
| D823 | 4.1 | 15.2 | Yes | 100-150 | — | S | S, L, G± | 106 | 34 | Skin GVHD, ET1 |
| D960 | 3.3 | 12.6 | Yes | 100-150 | — | NA | S, L, G | 72 | 25 | Pneumonia and meningitis |
| D962 | 2.6 | 15 | Yes | 5-150 | — | NA | ;— | 7 | 17 | Intussusception, septicemia, ET1 |
| D967 | 3.7 | 10.3 | Yes | 100-150 | S, G | NA | S, L, G | 48 | 38 | Pneumonia, ET1 |
| D988 | 3.4 | 11.9 | Yes | 100-150 | — | — | (chronic) G | >540 | 30 | ET2 |
| D992 | 3.6 | 9.8 | Yes | 100-150 | — | — | S, L, (chronic) G± | >420 | 19 | ET2 |
| E071 | 3.8 | 11.2 | Yes | 100-150 | — | — | L, G± | >420 | 38 | ET2 |
| E072 | 4.0 | 13.6 | Yes | 100-150 | — | — | S±, L, (chronic) G± | >510 | 29 | ET2 |
| E223 | 3.7 | 15.8 | Yes | 100-150 | — | S± | S, L, (chronic) G | >420 | 26 | ET2 |
| Group 4 | ||||||||||
| E119 | 2.2 | 9.2 | Yes | 100-150 | — | — | S±, L, (chronic) G | >316 | 23 | ET2 |
| E168 | 2.7 | 8.8 | Yes | 100-150 | — | S | S, L | 119 | 18 | Skin GVHD, ET1 |
| E171 | 3.6 | 9.4 | Yes | 100-150 | — | S | S, L, G± | >224 | 8 | ET2 |
| E207 | 4.0 | 6.3 | Yes | 100-150 | — | S± | S, L, (chronic) G | >216 | 21 | ET2 |
| E210 | 4.1 | 17.1 | Yes | 100-150 | L | NA | S, L, (chronic) G | 95 | 41 | Infection, GVHD, renal failure |
| E211 | 3.5 | 15.5 | Yes | 100-150 | — | NA | S±, G | 38 | 25 | Meningitis, ET1 |
Group 1: MMF 10 mg/kg SC twice daily (20 mg/kg/d), from days 0-27.
Group 2: MMF 10 mg/kg SC twice daily (20 mg/kg/d), from days 0-27, CSP 10 mg/kg IV twice daily (20 mg/kg/d) from days 0-9, 15 mg/kg by mouth, twice daily (30 mg/kg/d) from days 10-27.
Group 3: MMF 6 mg/kg SC twice daily (12 mg/kg/d), from days 0-2, 10 mg/kg SC twice daily (20 mg/kg/d) from days 3-27; CSP 10 mg/kg IV twice daily (20 mg/kg/d) from days 0-9, 15 mg/kg by mouth twice daily (30 mg/kg/d) from days 10-27.
Group 4: MMF 6 mg/kg SC twice daily (12 mg/kg/d), from days 0-2, 10 mg/kg SC twice daily (20 mg/kg/d) from days 3-20; CSP 5 mg/kg IV twice daily (10 mg/kg/d) from days 0-5, 15 mg/kg by mouth twice daily (30 mg/kg/d) from days 6-20, 7.5 mg/kg twice daily (15 mg/kg/d) from days 21-45, 5 mg/kg by mouth twice daily (10 mg/kg/d) from days 46-75, 3 mg/kg by mouth twice daily (6 mg/kg/d) from days 76-100.
Abbreviations: ET1, euthanized due to poor condition; ET2, euthanized at completion of the study; G, gut; L, liver; S, skin.
All donor engraftment, as determined by microsatellite markers.19