Pharmacokinetics of CAMPATH-1H in BMT patients

CAMPATH-1 (CD52)Abs are used in stem-cell transplantation for prevention of GvHD and rejection. The humanized Ab CAMPATH1H has recently replaced the rat Ab CAMPATH-1G. There was a concern whether it might have a longer half-life in vivo and, possibly, cause prolonged immunosuppression post-transplant.

Serum samples were collected pre- and post-transplant from patients receiving CAMPATH-1H at 10 mg/day according to two protocols: (A) from Day -5 to Day +4 (total dose, 100 mg), (B) from Day -10 to Day -6 (total dose, 50 mg). The Ab concentrations were measured using an immunofluorescence assay.

Lymphocytes were substantially depleted by the second day of treatment and were below 0.1 x 10(9)/L by the day of transplant and for at least 1 month post-transplant. By Day 90 there was a greater recovery in Group B, to a median of 0.32 x 10(9)/L compared with 0.25 x 10(9)/L in Group A. By Day 180, both groups had recovered to approx 0.52 x 10(9)/L. Serum concentrations of CAMPATH-1H on the day of transplant were well above the level necessary for opsonization of lymphocytes. The peak Ab concentration was 6.1 micro g/mL in Group A and 2.5 micro g/mL in Group B. CAMPATH-1H could be detected in Group A for 23 days post-transplant, significantly longer than in Group B (11 days). The terminal half-life in the two groups was similar (range 15-21 days) and contrasts with the half-life of < 1 day previously estimated for CAMPATH-1G. There were no cases of graft failure and the incidence of GvHD was similar in the two groups.

The humanized Ab CAMPATH-1H appears to persist in the circulation for longer than the original rat Ab CAMPATH-1G. This might contribute to delayed lymphocyte recovery and prohibit the use of early donor-lymphocyte infusions. A short course of treatment given early pre-transplant is likely to be preferable to the extended course given both pre- and post-transplant.