Michael Gottlieb

Allograft Tolerance after Total Lymphoid Irradiation (TLI)

The ability to induce permanent and specific transplantation tolerance in neonatal mice was first reported by Medawar and his colleagues {Medawar 1953, Billingham & Brent 1956) more than 25 years ago. Since then, several models of tolerance induction in adult laboratory animals have been developed (Binz & Wigzell 1976, Muller-Rucholtz et al. 1976, Von Boehmer et al. 1976, Yunis et ai. 1976), but as yet none have had successful clinical application. During the past several years, we developed a regimen for the induction of transplantation tolerance which allows for the permanent survival of BM, skin and heart allografts in both inbred and outbred adult animals which differ at the major histocompatibility genetic region. The tolerization regimen is based upon the use of total lymphoid irradiation (TLI), a radiotherapy technique which has been used to treat lymphoid malignancies in humans (Kaplan 1972). TLI has few severe side effects, and the mortality rate associated with this procedure is negligible (Kaplan 1972). We review here the essential features of our experimental findings, and suggest that this regimen merits further investigation with regard to applicability to clinical bone marrow and organ transplantation.

The treatment of intractable rheumatoid arthritis with lymphoid irradiation

Abstract Subdisphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdispbragmatic lymphoid tissues in fractionated doses of 150–250 rod each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.