Liver, Kidney, and Thoracic Organ Transplantation Under FK 506

Abstract

The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93,3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under .FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cycIosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index.

Incidence of de novo cancer and lymphoproliferative disorders after liver transplantation in relation to age and duration of follow-up

“…The cumulative number of years of follow-up is also unknown, and this makes it difficult to calculate the actuarial risk. 2,6,[19][20][21] In this respect, data from single centers with long-term follow-up have become an important source of information for the incidence and nature of de novo cancers, which can then be compared with surveillance epidemiological end results data. Furthermore, these data can be presented as a standard incident ratio (SIR).…”

Disease gravity and urgency of need as guidelines for liver allocation*1

“…This separate study was undertaken so that we might have a better assessment of survival expectation at the various risk levels than was available, even in the current literature. Just before this series began, there had been two significant improvements with a potential impact on high-risk (as well as all other) patients: University of Wisconsin solution in 1988 (2,3), and, perhaps more important, FK 506, which after July 1989 could be used for primary immunosuppression or for the rescue of patients whose initial baseline drug was cyclosporine (4,5).…”

Tacrolimus (FK506) and the pharmaceutical/academic/regulatory gauntlet

“…[10][11][12] It had been learned that the three major side effects of the drug (nephrotoxicity, neurotoxicity, and diabetogenicity) were comparable to cyclosporine. Hypertension and hyperlipidemia were less than in historical cyclosporine controls, and the cosmetic effects of cyclosporine (hirsutism, gingival hyperplasia, and facial brutalization) had not been seen.…”

“…Hypertension and hyperlipidemia were less than in historical cyclosporine controls, and the cosmetic effects of cyclosporine (hirsutism, gingival hyperplasia, and facial brutalization) had not been seen. [10][11][12][13][14] Although it was recognized that these first patients had been started on too much tacrolimus, complications of overdosage had been minimized by using the characteristic side effects cited above to determine dose ceilings from the first day of treatment onward. Rejection established the dose floor.…”