Effect of mycophenolate mofetil in heart transplantation.
OBJECTIVE
To study the effect of mycophenolate mofetil (MMF), a new immunosuppressive drug that acts by inhibiting de novo pathways of purine synthesis, and rabbit antithymocyte globulin (RATG) on the lymphocyte subpopulation after heart transplantation.


METHODS
A review of clinical and laboratory records.


METHODS
The Montreal Heart Institute.


METHODS
Thirty-one patients who underwent heart transplantation. In 9 patients, neoral cyclosporine, prednisone and azathioprine were administered (group 1). In 14 patients RATG was added during the first 3 postoperative days (group 2) and in 8 patients RATG and combination immunosuppression was given, but MMF was used instead of azathioprine (group 3). The demographic characteristics of donors and recipients were similar among the 3 groups.


METHODS
The proportion of CD2, CD4 and CD8 receptor-positive lymphocytes, expressed as a mean (and standard deviation) percentage of the total lymphocyte population, measured at 7, 15 and 30 days and 6 months after transplantation.


RESULTS
At 7 days after transplantation, CD2 lymphocytes averaged 55% (18%), 16% (15%) and 14% (11%) in groups 1, 2 and 3 respectively (p < 0.05), CD4 averaged 36% (11%), 9% (12%) and 7% (8%) in groups 1, 2 and 3 (p < 0.05), and CD8 averaged 14% (6%), 4% (3%) and 4% (3%) in groups 1, 2 and 3 (p < 0.05). At 15 days after transplantation CD2 averaged 69% (10%), 42% (16%) and 47% (20%) in groups 1, 2 and 3 respectively (p < 0.05), and CD8 averaged 16% (7%), 16% (6%) and 19% (7%) (p = NS). At 30 days after transplantation the percentages of CD2, CD4 and CD8 lymphocytes were similar among the groups. The freedom rate from acute rejection averaged 22% (14%), 9% (8%) and 50% (18%) (p < 0.05) in groups 1, 2 and 3 at 6 months after transplantation, and the freedom rate from infection averaged 56% (17%), 36% (13%) and 38% (17%) for the 3 groups at this time period (p = NS).


CONCLUSIONS
A short course of RATG causes severe, transitory depletion of CD2, CD4 and CD8 lymphocyte subpopulations. MMF decreases the incidence of early acute rejection after heart transplantation without affecting the lymphocyte subpopulation when compared with azathioprine.
Mathieu
P
P
Department of Surgery, Montreal Heart Institute, Que.
Carrier
M
M
White
M
M
Pellerin
M
M
Perrault
L
L
Pelletier
G
G
Robitaille
D
D
Pelletier
L C
LC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D018801:CD2 Antigens / Q000187:drug effects*; D018791:CD4 Lymphocyte Count / Q000187:drug effects*; D016827:CD8 Antigens / Q000187:drug effects*; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018655:Lymphocyte Count / Q000187:drug effects*; D016131:Lymphocyte Subsets / Q000187:drug effects*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011817:Rabbits; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000961:Antilymphocyte Serum; D018801:CD2 Antigens; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone