Sb. Rasaiah et al., A comparison of daclizumab to ATGAM induction in simultaneous pancreas-kidney transplant recipients on triple maintenance immunosuppression, CLIN TRANSP, 14(4), 2000, pp. 409-412
Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab d
irected against the alpha chain of the interleukin-2 receptor (IL2R). Inhib
iting the amplification of the immune response by blocking IL2R can reduce
the frequency of acute rejection without the attendant risk of infection.
The purpose of this retrospective study was to compare DAC to antithymocyte
(ATGAM) induction in 24 simultaneous pancreas-kidney (SPK) transplants per
formed between September 1995 and September 1998. The primary endpoints wer
e the incidence within 6 months posttransplant of: 1) biopsy-proven acute r
ejection; and 2) infection. The two groups (DAC, n = 12; ATGAM, n = 12) wer
e matched on age, race, ESRD, number of HLA mismatches, PRA level, and cold
ischemia time. DAC (1 mg/kg) was given on the day of transplant, then ever
y other week (a total of five doses); ATGAM (15 mg/kg) was given on post-tr
ansplant day 1, then daily for 7-10 d. Immunosuppressive therapy consisted
of cyclosporine (Neoral(R) - 8-10 mg/kg/d) or Prograf(R) (0.16-0.2 mg/kg/d)
, mycophenolate mofetil (CellCept(R) - 2-3 g/d) and steroids.
Of the 12 DAC patients, 3 patients (25%) had biopsy-proven acute rejection
versus 8/12 (67%) of the ATGAM patients. The time to acute rejection was si
gnificantly different by group (DAC = 110 d; ATGAM = 26 d). There was a red
uction in the number of patients receiving antilymphocyte drugs for moderat
e to severe rejection (DAC = 2/12; ATGAM = 4/12), with 2 of the 4 ATGAM pat
ients experiencing more than two episodes of biopsy-proven rejection. There
was an increase in infection by group (DAC = 4/12; ATGAM = 7/12): total of
three septic infections occurred in the ATGAM group opposed to none in the
DAC group. Patient, pancreas, kidney 6-month survival rates were 100% for
both groups.
We conclude that DAC induction coupled with triple immunosuppressive therap
y reduces the incidence of rejection in SPK transplant patients. The time t
o acute rejection was prolonged in the DAC group compared with the ATGAM gr
oup without the attendant risks of rejection.