THROMBOCYTOPENIA AND PLATELET ASSOCIATED IMMUNOGLOBULIN (PAIg) IN PATIENTS RECEIVING ACTINOMYCIN D. (AMD)

Abstract

of P e d i a t r i c s and Urology, Boston. We have p r e v i o u s l y described r e s u l t s w i t h a novel form o f adoptive immunotherapy using i n v i t r o immunized ( I V I ) autologous lymphocytes. We now r e p o r t r e s u l t s from an on-going study using an improved v e r s i o n of t h a t method. P a t i e n t lymphoc y t e s a r e d e p l e t e d o f suppressor T -c e l l s and i n v i t r o immunized f o r 60 hours i n medium c o n t a i n i n g autologous serum, mixed lymphoc y t e c u l t u r e s u p e r n a t a n t and a 3M KC1 a.atologous twnor e x t r a c t . The r e s u l t a n t I V I c e l l s a r e washed, d e p l e t e d again of suppressor c e l l s and i n f u s e d i n t o t h e p a t i e n t . A l l p a t i e n t s a l s o r e c e i v e c i m e t i d i n e t o block i n vivo suppressor c e l l s . P a t i e n t s w i l l be t r e a t e d monthly f o r 6 months. To d a t e , 30 p a t i e n t s have received a t o t a l o f 113 c e l l i n f u s i o n s , a l l d e l i v e r e d on an o u t p a t i e n t b a s i s , (average of l o 9 I V I c e l l s / i n f u s i o n ) . Toxicity has been minimal, c o n s i s t i n g o n l y of mild, t r a n s i e n t f e v e r and c h i l l s accompanying 42 of t h e i n f u s i o n s ( 3 7 % ) . Twenty-one p a t i e n t s have reached t h e f i r s t e v a l u a t i o n t i m q o i n t a t 3 months. (M~=minor response;PR=partial response;CR=complete response) This approach t o immunotherapy is s a f e and appears t o be b i o l o g i c a l l y a c t i v e , i n t h a t 7 of 21 evaluable p a t i e n t s (33%) have evidence of s t a b l e d i s e a s e o r o b j e c t i v e response a f t e r only 3 months of t r e a t n e n t . We have p r e v i o u s l y described t h a t thymic hormones might h e u s e f u l i n t h e treatment of h i s t i o c y t o s i s -X . Based on t h o s e d a t a , t h e O f f i c e o f Orphan Products Development a t t h e FDA i s sponsoring a randomized, double-blind, placebo-controlled c l i n i c a l s t u d y t o determine i f Suppressin A, a mixture of thymic hormones t h a t s p e c i f i c a l l y induce t h e d i f f e r e n t i a t i o n o f suppress o r T-lymphocytes, i s b i o l o g i c a l l y a c t i v e i n histiocytosis-X. P a t i e n t s a r e randomized t o r e c e i v e e i t h e r Suppressin A o r placebo f o r 42 days, a f t e r which they a r e re-evaluated and t h e codebroken. To h e l p i n t h e e v a l u a t i o n of b i o l o g i c a l a c t i v i t y , f o u r d i s t i n c t c l i n i c a l s c o r i n g systems were c r e a t e d : 1)organ s p e c i f i c ; 2)whole body; 3 ) v i t a l systems ( r e s p i r a t o r y , h e p a t i c and hematopoetic f u n c t i o n ) ; and 4 ) o v e r a l l performance s t a t u s . The r e s u l t s t o d a t e from t h e i n i t i a l 1 3 p a t i e n t s who have completed t h e six-week t r e a t m e n t course i n t h i s on-going study a r e : Scoring System Suppressin A (N=8) TREATMENT OF HISTIOCYTOSIS-X WITH SUPPRESSIN- t a i n d i c a t e b i o l ...