Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros

Abstract

To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.