A RANDOMISED TRIAL OF TACROLIMUS (FK 506) VERSUS TOTAL LYMPHOID IRRADIATION (TLI) FOR THE CONTROL OF REPETITIVE REJECTION AFTER CARDIAC TRANSPLANTATION
A.M. Keogh, P.S. Macdonald, C. McCosker, C. Aboyoun, R.H. Arnold*, P.M. Spratt.
St. Vincent's Hospital, Sydney, New South Wales.
Recurrent acute cardiac rejection is a major cause of morbidity following cardiac transplantation. Our aim was to compare two treatment strategies for control of recurrent rejection: (1) switch from cyclosporine to FK506 versus (2) continuation of cyclosporine with a course of TLI. Thirteen male heart transplant recipients with recurrent rejection defined as either (a) 3 sequential episodes of rejection failing to clear with steroids or (b) 3 episodes of ISHLT grade 3a or higher rejection in the first 3 post-operative months, were randomised to FK506 (n = 6) or TLI (n = 7). FK506 was initiated at 0.05-0.15mg/kg/day and dose titrated to achieve whole blood levels (LSMS) of 8-12ng/mL. TLI (lymph node, spleen irradiation) was in 8 fractions of 6.4 Gy administered over 3 weeks. Each rejection episode of grade > 3a was treated with an oral steroid taper.
|
RESULTS |
Pre FK506 (n=6) |
Post FK 506 (n=6) |
Pre TLI (n=7) |
Post TLI (n=7) |
|
Mean no. rejections* |
3.2±0.4 |
0.7±0.8 |
3.4±0.8 |
0.1±0.4 |
|
Mean no. infections** |
1.2±1.0 |
0.5±0.4 |
1.0±0.8 |
1.0±1.2 |
|
Mean hospital days |
5.2 |
4.0 |
5.9 |
4.3 |
|
Days to randomisation |
54±24 |
- |
68±26 |
- |
|
WCC nadir (x109/L) |
- |
- |
- |
2.1±0.8 |
|
Days WCC <5x109/L |
- |
- |
- |
44.4±12.1 |
|
Serum creat mmol/L |
0.12±0.03 |
0.12±0.03 |
0.11±0.03 |
0.12±0.03 |
|
Cost Aus $ |
$8000 pa |
$800 (x1) |
* rejection of grade 3a or higher
** infections requiring treatment
There were no deaths, strokes or malignancies in either group at 12 months follow-up. One patient developed diabetes mellitus after FK506 was commenced.
Conclusion: Conversion to FK506 or a course of TLI are equipotent strategies, each preventing further rejection in recurrent rejections. There were no significant differences in infection rate and hospital readmission days. The cost of the two strategies is comparable given the cost saved by the cessation of cyclosporine in the FK506 group.
