Total lymphoid irradiation inmultiple sclerosis

areport oftheefficacy oftotal lymphoid irradiation (TLI)inthetreat- ment of chronicprogressive multiple sclerosis a further randomnsed double- blindplacebo-controlled studywas undertaken withtheintention ofentering 56patients. Intheeventitwaspossible to recruit only27patients ina 25 year period. Threepatients received active treatmentopenlyand 24 were ran- domisedtoeither active (14)orsham (10)treatment. Treatment was1980cGy tothelymphoidsystemandspleenor sham treatmentafterfullsimulation. The primaryoutcomemeasurewas a comparison ofthemean ratesofchange betweentreatmentgroupson the expandedKurtzkedisability scale (EDSS)overthetwo yearfollowup period. Patients werealsoassessed on otherclinical outcomemeasures,psy- chometry, andserial MRI ofthebrain. Active treatment resulted inaprofound and prolonged fallin T lymphocytes especially thosewiththeCD4 marker and a reversal inCD4:CD8ratio. No significant benefit wasdemonstrated on therateofclinical disease progression (EDSS).A smallbutsignificant benefit wasfoundonascoreofbladder function. No significant benefit wasdemonstrated onotherclinical orpsychometric indices oron subjective visual analogue scales. Therewasasmallbutsignificant differ- encein therateofaccumulation of lesions onbrainMRIfavouring thetreat- ment group.The treated grouphada higherincidence ofclinically relevant sideeffects, notably amenorrhoeaand infections: threedeaths(oneintheTLI group,twointheshamtreated group) occurred. A posthoccalculation indi- catesthatthestudyhada possible 35% riskofa false negative result usingthe principal outcomemeasure.The study fails toconfirmthepreviously reported clinical benefit ofTLI although there may bea minorbenefit on disease pro- gression as indicated by MRI lesion counts.It is concluded thatTLI cannot berecommendedfortheroutine treat- ment ofchronicprogressive multiple sclerosis butthebeneficial effect onMRI lesions, thoughmodest,suggests that further research intoimmune modula- tionofthiscondition maybeworthwhile.