Effect of Crossmatching on Outcome in Organ Transplantation

Abstract

The complement-dependent cytotoxicity (CDC) crossmatch and the flow cytometry crossmatch (FCXM) are both used prospectively in renal transplantation, and their use is under evaluation in other types of major organ transplantation. The FCXM is the more sensitive method and better predicts outcome in second and subsequent renal allografts. Improved survival has unmasked the detrimental effect of a positive crossmatch on outcome in liver transplantation. Because of the urgent need of liver transplant candidates, it is unrealistic to defer transplantation until a crossmatch-negative donor is found; however, additional therapeutic measures may be taken to improve outcome for crossmatch-positive liver recipients. Some reports suggest that prospective crossmatching may improve outcome for sensitized heart recipients, and, additionally, recent studies have demonstrated that HLA compatibility between donor and recipient is an independent variable affecting survival after heart transplantation, prompting a reassessment of the current practice of transplanting hearts without consideration of the HLA match.

At the University of California, San Diego, the Histocompatibility and Immu-nogenetics Laboratory aims to provide timely, accurate, cost-effective, and clinically relevant pretransplant testing. Policies regarding pretransplant testing have been developed based on an assessment of what is clearly established to improve transplant success. Crossmatch procedures for renal and renal-pancreas transplantation include the standard CDC and long-incubation CDC crossmatches for all recipients, plus FCXM for regrafted recipients, all with T lymphocytes. Sera for crossmatching include the most recent and most reactive within 1 year and are used unmodified and modified with DTT. A positive crossmatch with unmodified serum that converts to negative with DTT is regarded as clinically insignificant. Standard and long-incubation CDC crossmatches are performed for liver, heart, and heart-lung transplantation but may be performed retrospectively, as crossmatch positivity is not a contraindication to transplantation.

These policies are under continuous review and will be modified as new information about the relevance of the transplant crossmatch to clinical outcome becomes available. Other transplant centers will look at the same body of evidence in the literature and come to different conclusions about what is the best pretransplant testing. This diversity of approaches is useful and permits comparisons among centers regarding the effect of particular pretransplant testing on outcome in major solid organ transplantation.

Key Words::

• HLA
• flow cytometry
• complement
• cytotoxicity
• histocompatibility
• immunology
• lymphocyte
• rejection