Abstract
Background. Preformed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong patient waiting time for kidney transplantation. We hypothesized that rituximab (RTX) could reduce PRA via B-cell depletion. This initial study reports the safety, pharmacokinetics, and pharmacodynamics of RTX in patients with end-stage renal failure. Methods. The study was an investigator-initiated single-dose, dose-escalation phase I trial of RTX in chronic dialysis patients (PRA >50%). It was approved by the Institutional Review Board and the Food and Drug Administration. Nine subjects were treated with a single dose of RTX (n=3 per group) at 50, 150, or 375 mg/m2. Peripheral lymphocyte cell surface markers and HLA Ab levels (%PRA and titers) were tested using flow cytometry. Results. There were four significant adverse events: a suspected histoplasmosis infection; two Tenchkoff dialysis catheter infections; and fever (38.7°C) during infusion. At 2 days after RTX therapy, there was depletion of CD19+ cells (pre-RTX 181±137 vs. post-RTX 12±5.6, P=0.006). In 2 (22%) of 9 subjects, there was no appreciable change in PRA. Among the other seven patients, one had a decrease in PRA from 87% to 51% with a concurrent decrease in fluorescence intensity; five patients had changes in histogram architecture suggesting loss of antibody specificity; and one patient had a fourfold decrease in PRA titer from 1:64 to 1:16 at 6 months after treatment. In addition, one of the seven patients converted a donor-specific crossmatch to negative and underwent a successful living donor kidney transplantation. Conclusions. RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 542-548 |
| Number of pages | 7 |
| Journal | Transplantation |
| Volume | 77 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 27 2004 |
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ASJC Scopus subject areas
- Transplantation
Cite this
Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation : 1. Safety, pharmacodynamics, and pharmacokinetics. / Vieira, Carlos A.; Agarwal, Avinash; Book, Benita K.; Sidner, Richard A.; Bearden, Christopher M.; Gebel, Howard M.; Roggero, Anthony L.; Fineberg, Naomi S.; Taber, Timothy; Kraus, Michael A.; Pescovitz, Mark D.
In: Transplantation, Vol. 77, No. 4, 27.02.2004, p. 542-548.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation
T2 - 1. Safety, pharmacodynamics, and pharmacokinetics
AU - Vieira, Carlos A.
AU - Agarwal, Avinash
AU - Book, Benita K.
AU - Sidner, Richard A.
AU - Bearden, Christopher M.
AU - Gebel, Howard M.
AU - Roggero, Anthony L.
AU - Fineberg, Naomi S.
AU - Taber, Timothy
AU - Kraus, Michael A.
AU - Pescovitz, Mark D.
PY - 2004/2/27
Y1 - 2004/2/27
N2 - Background. Preformed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong patient waiting time for kidney transplantation. We hypothesized that rituximab (RTX) could reduce PRA via B-cell depletion. This initial study reports the safety, pharmacokinetics, and pharmacodynamics of RTX in patients with end-stage renal failure. Methods. The study was an investigator-initiated single-dose, dose-escalation phase I trial of RTX in chronic dialysis patients (PRA >50%). It was approved by the Institutional Review Board and the Food and Drug Administration. Nine subjects were treated with a single dose of RTX (n=3 per group) at 50, 150, or 375 mg/m2. Peripheral lymphocyte cell surface markers and HLA Ab levels (%PRA and titers) were tested using flow cytometry. Results. There were four significant adverse events: a suspected histoplasmosis infection; two Tenchkoff dialysis catheter infections; and fever (38.7°C) during infusion. At 2 days after RTX therapy, there was depletion of CD19+ cells (pre-RTX 181±137 vs. post-RTX 12±5.6, P=0.006). In 2 (22%) of 9 subjects, there was no appreciable change in PRA. Among the other seven patients, one had a decrease in PRA from 87% to 51% with a concurrent decrease in fluorescence intensity; five patients had changes in histogram architecture suggesting loss of antibody specificity; and one patient had a fourfold decrease in PRA titer from 1:64 to 1:16 at 6 months after treatment. In addition, one of the seven patients converted a donor-specific crossmatch to negative and underwent a successful living donor kidney transplantation. Conclusions. RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.
AB - Background. Preformed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong patient waiting time for kidney transplantation. We hypothesized that rituximab (RTX) could reduce PRA via B-cell depletion. This initial study reports the safety, pharmacokinetics, and pharmacodynamics of RTX in patients with end-stage renal failure. Methods. The study was an investigator-initiated single-dose, dose-escalation phase I trial of RTX in chronic dialysis patients (PRA >50%). It was approved by the Institutional Review Board and the Food and Drug Administration. Nine subjects were treated with a single dose of RTX (n=3 per group) at 50, 150, or 375 mg/m2. Peripheral lymphocyte cell surface markers and HLA Ab levels (%PRA and titers) were tested using flow cytometry. Results. There were four significant adverse events: a suspected histoplasmosis infection; two Tenchkoff dialysis catheter infections; and fever (38.7°C) during infusion. At 2 days after RTX therapy, there was depletion of CD19+ cells (pre-RTX 181±137 vs. post-RTX 12±5.6, P=0.006). In 2 (22%) of 9 subjects, there was no appreciable change in PRA. Among the other seven patients, one had a decrease in PRA from 87% to 51% with a concurrent decrease in fluorescence intensity; five patients had changes in histogram architecture suggesting loss of antibody specificity; and one patient had a fourfold decrease in PRA titer from 1:64 to 1:16 at 6 months after treatment. In addition, one of the seven patients converted a donor-specific crossmatch to negative and underwent a successful living donor kidney transplantation. Conclusions. RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.
UR - http://www.scopus.com/inward/record.url?scp=10744232375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744232375&partnerID=8YFLogxK
U2 - 10.1097/01.TP.0000112934.12622.2B
DO - 10.1097/01.TP.0000112934.12622.2B
M3 - Article
C2 - 15084932
AN - SCOPUS:10744232375
VL - 77
SP - 542
EP - 548
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 4
ER -