To induce or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?
BACKGROUND
Induction immunosuppression utilizing lymphocytolytic agents in the early peri-operative period has a number of theoretical and practical advantages and disadvantages. However, the efficacy of cytolytic agents as induction therapy remains unproven.


METHODS
To assess the current impact of induction therapy in heart transplantation, we queried a multi-institutional database regarding the frequency of use, type of agent, duration of therapy and outcomes of 6,553 patients transplanted from 1990 to 2001. A study group of 5,897 patients were identified who survived the first 48 hours post-transplant and received either no induction therapy (n = 4,161) or induction with OKT3 or anti-thymocyte preparations (n = 1,736).


RESULTS
By multivariate analysis, risk factors for rejection death were identified and then applied to a model of overall mortality. Among patients with a 1-year risk of rejection death at >5%, induction therapy provided a survival advantage, but survival with induction was decreased when the risk of rejection death was <2%. Specific patient sub-sets that received a survival benefit in the current era with induction included younger patients of black race with >/=4 HLA mismatches and long-term (>6 months) support on a ventricular assist device (VAD).


CONCLUSIONS
Use and application of induction therapy continues to be controversial in heart transplantation. At present, this approach appears to be beneficial in selected patients who are at high risk for rejection death, but likely detrimental in patients who are at low risk for rejection death. Those with a combination of longer term VAD support, of black ethnicity, and having extensive HLA mismatching are most likely to benefit from cytolytic induction therapy.
Higgins
R
R
University of Alabama at Birmingham, Division of Cardiothoracic Surgery, Birmingham, Alabama 35294, USA.
Kirklin
J K
JK
Brown
R N
RN
Rayburn
B K
BK
Wagoner
L
L
Oren
R
R
Miller
L
L
Flattery
M
M
Bourge
R C
RC
D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D003657:Decision Making; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods* / Q000706:statistics & numerical data; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D016853:Muromonab-CD3 / Q000627:therapeutic use; D009656:North America / Q000453:epidemiology; D019990:Perioperative Care / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013601:T-Lymphocytes / Q000276:immunology
D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3