Effect of mycophenolate mofetil in heart transplantation

OBJECTIVE: To study the effect of mycophenolate mofetil (MMF), a new immuno suppressive drug that acts by inhibiting de novo pathways of purine synthes is, and rabbit antithymocyte globulin (RATG) on the lymphocyte subpopulatio n after heart transplantation. DESIGN: A review Of clinical and laboratory records. SETTING: The Montreal Heart Institute. PATIENTS: Thirty-one patients who underwent heart transplantation. In 9 pat ients, neoral cyclosporine, prednisone and azathioprine were administered ( group 1). In 14 patients RATG was added during the first 3 postoperative da ys (group 2) and in 8 patients RATG and combination immunosuppression was g iven, but MMF was used instead of azathioprine (group 3). The demographic c haracteristics of donors and recipients were similar among the 3 groups. MAIN OUTCOME MEASURES: The proportion of CD2, CD4 and CD8 receptor-positive lymphocytes, expressed as a mean land standard deviation) percentage of th e total lymphocyte population, measured at 7, 15 and 30 days and 6 months a fter 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), CD 4 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 1 6% (7%), 16% (6%) and 19% (7%) (p = NS). At 30 days after transplantion 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, an d 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 lym phocyte subpopulation when compared with azathioprine.