Total lymphoid irradiation in patients with refractory rheumatoid arthritis

Abstract

Eleven patients with rheumatoid arthritis that had been refractory to conventional drug therapy were treated with total lymphoid irradiation (TLI). Followup continued for 6 months in 9 patients, 12 months in 6 patients, and 24 months in 3 patients. At 6 and 12 months post‐TLI, a significant improvement in clinical disease activity was demonstrated. Side effects noted during TLI included fatigue, nausea, diarrhea, and vomiting. One patient died of cardiorespiratory arrest, 2 patients died of kidney failure secondary to generalized amyloidosis, and 1 patient died of septic shock secondary to a multilocular septic arthritis. One patient experienced 2 episodes of septic arthritis; 2 patients manifested delayed wound healing. Immunologic assessments showed consistent lymphopenia in all patients. T lymphocyte subsets decreased after TLI, and showed a transient increase at 6 months post‐TLI. The suppressed mitogen responsiveness, which was noted 2 months after irradiation, was found to increase almost to the pre‐TLI levels at 12 months. The observed increase in morbidity and mortality after TLI is evidence that discourages the use of this therapeutic technique, at least in its present form.

Treatment of rheumatoid arthritis with total lymphoid irradiation: Long-term survival

“…Frequent short-term toxic events have included herpes zoster and bacterial infections, reversible bone marrow suppression, and persistent lymphopenia. Deaths in TLI-treated patients were due to extensive rheumatoid lung disease, infection, or myocardial infarction (MI) in most cases, but 2 deaths were reported to be due to amyloidosis (4).…”

“…Fractionated TLI, comprising 2,000 centigray (cGy) applied to the supra-and subdiaphragmatic lymph nodes and spleen, came into use to treat intractable RA Ͼ20 years ago and initial results were reported by our institution and by others (3)(4)(5)(6). This therapy markedly reduces T cells, which are thought to play an important role in the pathogenesis of the disease (1).…”

Rheumatoid Arthritis in the Aged

“…However, adverse effects, particularly hypertension and renal disease were common. However, this form of therapy is associated with increased mortality, which may be age-related (Nusslein et al 1985;Sherrer et al 1987). Intractable RA may improve after total lymphoid irradiation (Strober et al 1985;Tanay et al 1987).…”

Transfer of rheumatoid arthritis into severe combined immunodeficient mice. The pathogenetic implications of T cell populations oligoclonally expanding in the rheumatoid joints.

“…(c) Partial elimination or inhibition of T cells by immunosuppressive drugs and anti-T cell antibodies can ameliorate the disease (12)(13)(14)(15)(16). In the mouse model such as collagen-induced arthritis (CIA), the disease process is T cell mediated, necessitating a particular combination of TCR/V13 genes and MHC class II genes and the efficacy of anti-TCR/V13 therapy has been demonstrated (17)(18)(19)(20)(21).…”