Table 2.
| A: Comparison of Regimens 1, 2, and 3 |
|---|
| Regimen 1 (n=3): |
| Induction: ATG, CVF (a), anti-CD20mAb, methylprednisolone |
| Maintenance: Anti-CD154mAb, MMF, methylprednisolone, heparin, ketorolac, ganciclovir (i.v. daily) |
| Regimen 2 (n=2): |
| Induction: ATG, CVF*, anti-CD20mAb, methylprednisolone |
| Maintenance: CTLA4-Ig (abatacept), MMF, methylprednisolone, heparin, ketorolac, ganciclovir (i.v. daily) |
| Regimen 3 (n=2): |
| Induction: ATG, methylprednisolone |
| Maintenance: Anti-CD40mAb + CTLA4-Ig (belatacept), rapamycin (B5512) or tacrolimus (B5712), methylprednisolone, low molecular weight heparin (c), ganciclovir (i.v. ×2 weekly), valganciclovir (p.o. daily) |
| B: Details of immunosuppressive and supportive therapy | ||
|---|---|---|
| Dose | Duration | |
| Induction therapy | ||
| Thymoglobulin (ATG) (a) | 1–10 mg/kg i.v. | days -3, -1 a |
| Cobra venom factor | 100 units/day i.v. | days -1, 0, 1 |
| Methylprednisolone | 5 mg/kg i.v. | before each dose of ATG, and on days -1, 0, 1 |
| Anti-CD20mAb (b) | 20 mg/kg i.v. | Single dose on day -2 |
| Maintenance costimulation blockade | ||
| Anti-human CD154mAb (c) | 25 mg/kg i.v | days -1, 0, 4, 7, 10, 14, 19 and then every 7 days (Regimen 1 only) |
| OR | ||
| Abatacept (d) | 25 mg/kg i.v | days -1, 0, 2, 4, 7, 10, 14, 21 and then every 7 days (Regimen 2 only) |
| OR | ||
| Anti-CD40mAb (e) Belatacept (f) |
25 mg/kg i.v. 20 mg/kg i.v. |
days -1, 0, 4, 7, 10, 14 and then every 7 days. days -1, 0, 4, 7, 14 and then every 14 days (Regimen 3 only) |
| Maintenance pharmacologic immunosuppressive and supportive therapy | ||
| MMF | 25–110 mg/kg/day | continuous i.v. infusion from day -3 (to maintain a constant blood level of 3–5 µg/mL) |
| Rapamycin | 0.01 mg/kg i.m. ×2/day | to maintain a blood trough level of 10–15 ng/mL |
| Tacrolimus | 0.05-0.03 mg/kg i.m. ×2/day | to maintain a blood trough level of 10–15 ng/mL |
| Methylprednisolone | 5 mg/kg i.m. daily | tapering to 0.25 mg/kg/day i.m. at 6 weeks |
| Heparin (g) | 5–50 U/kg/h i.v. | from day 0 (to maintain ACT at 200–250sec from day 3) (Regimens 1 and 2 only) |
| Low molecular weight heparin | 700 IU daily i.m. | from day 1 (Regimen 3 only) |
| Ketorolac (h) | 0.5 mg/kg i.v. | before each dose of anti-CD154mAb or CTLA4-Ig, beginning on day -1 (Regimens 1 and 2 only) |
| Ganciclovir | 5 mg/kg/day i.v. | in Regimen 3, it was administered daily for 14 days and then ×2 weekly |
| Valganciclovir | 15 mg/kg/day ×2 daily p.o. | in Regimen 3 only |
Cobra venom factor was administered to one Group A baboon that had a particularly high level of anti-nonGal IgM, and so for consistency was administered to all 4 baboons in Group A and 1 in Group B. We subsequently concluded that cobra venom factor is unnecessary when adequate complement-regulation is provided by the graft, and it was omitted in the remaining 2 baboons in Group B.)
Rapamycin and tacrolimus were tested to determine whether there was a major difference in outcome.)
Although low molecular weight heparin alone is unlikely to prevent TM, we felt it might augment the effect of the expression of TBM.
Day-1 dose of ATG (Rabbit derived, Genzyme, Cambridge, MA) was given only if needed to reduce lymphocyte count <500×103/mm3.
Anti-CD20mAb (Rituxan, Biogen Idec/Genentech, South San Francisco, CA)
Anti-CD154mAb (Hu5c8 in a mouse/human IgG1 chimeric; NIH NHP Reagent Resource, Boston, MA) kindly provided by Dr. Keith Reimann.
Abatacept (Orencia; BMS, Princeton, NJ)
Anti-CD40mAb (2C10R4; NIH NHP Reagent Resource) kindly provided by Dr. Keith Reimann.
Belatacept (Nulojix; BMS, Princeton, NJ)
Heparin and ketorolac were given in Regimens 1 and 2 only.