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#020287-1
L A J0L L A ,F eb . 9 -- S cripps Clinic and Resear chFoundation
p h y s i c i a n sa r e t r e a t i n g l e u k e m i ap a t i e n t s w i t h a p r o m i s i n gb u t
e x p e r i me n ta b
l o n emarro wtra nsplant technique.
D eve l op e at
d th e N o rri s Cotton CancerCenter , Dar tm outh- Hitchcoc k
M e d i c a l C en te r, N .H ., the methoduses m onoclonalantibodies to pur ge the
m a r r o wo f l e u k e m i ac e l l s , a n d i s a u t o l o g o u s- m e a n i n gt h a t t h e p a t i e n t ' s
ownmamowis extracted, treated and rep'laced.Standardbonemamow
t r a n s p l an t te ch n i qu e su se the m ar r owof a br other or sister , and often
'lead
t o c o m p l i c a t i o n s u c ha s g r a f t - v s . - h o s t d i s e a s ea n d i n f e c t i o n .
u s i n g mon o cl on aan
l ti bo dies developedby Dr . Edwar dBall, headof
t h e D a r tmo u thMed i calS ch o o l' s clinical im m unology
r esear chpr ogr am ,the
t h r e e - y ea r D a rtmo u th /S cri p ps
C' linic study has tr eated 22 patients with
a d v a n c edacu te mye'l o g e n o lueukem
s
ia,the type r esponsiblefor about 80
p e r c e n to f a l l a d u l t a c u t e l e u k e m i ac a s e s .T h em e d i a ns u r v i v a l i n t h i s
p a t i e n t grou pw as three to four tim es the ' lengthachievedwith standar d
chemotherapy
treatment.
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.|987
Feb. 9,
P a g e2
" T h er e s u l t s i n p a t i e n t s w i t h a d v a n c eddi s e a s ea r e e n c o u r a g i n g , "
s a i d D r . R o b e r tM c M i l l a n ,d i r e c t o r o f t h e S c r i p p sC l i n i c W e i n g a r t
T r a n s p l a n t a t i o nC e n t e r .B e c a u s o
ef t h i s , a p i l o t s t u d y i s s t a r t i n g u s i n g
a u t o l o g o u st r a n s p l a n t a t i o ni n p a t i e n t s i n f i r s t r e m i s s i o n .
Bal l , w ho si x ye a rs a g o beganthe tim e- consum ing
r esear chthat led
o tf t h e m o n o c l o n aal n t i b o d i e s ,w a sj o i n e d i n d e v e l o p i n g
to the developmen
t h e t r a nsp l an t prog ramby D r. GibbonsCor nwelland Dr . Letha M ills of
D a r t m o u th 'she matoog
l y/o n coogy
l section.
"A Itho u g hth e prog rami s only thr ee year s o' ld, we knowthat this
t r e a t m en t do e s prod u ceprol ongedr em issionsin som epatients without
m a i n t e n a n cceh e m o t h e r a p ys, "a i d C o r n w e l l ." I n a d d i t i o n , i t o f f e r s
p r o t e n t i a l f o r a c u r e , a l t h o u g ha t t h i s t i m e i t ' s t o o e a r l y t o e v a l u a t e
w h a t p e rcen ta g eo f p a ti en ts will r em ainfr ee of the disease."
O t h e r t h a n M c M i l l a n ,p h y s i c i a n si n v o l v e da t S c r i p p sC l i n i c a r e
D r . E r n e s t B e u t l e r , c h a i r m a no f t h e b a s i c a n d c l i n i c a l r e s e a r c h
d e p a r t m e nat n d h e a do f t h e h e m a t o l o g y / o n c o l odgi vy i s i o n , D r . W i l l i a m
M i l l e r , h e m a t o l o g y / o n c o l odgi vy i s i o n , a n d D r . L i n d a T h o m p s o n
im
, munology
division.
leukem iaare
"P a ti en ts w h oh a ve on ce r elapsedwith acute m yelogenous
n e v e r c ure d b y ch e moth e rap y,"
said Beutler . "This appr oachoffer s new
h o p e t o su ch p a ti en ts."
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Feb.9, l9B7
P a g e3
L e uke mi ai s a d i sea sech ar acter izedby an abnor m alincr ease in the
'l eu ko cyte s,
numbeo
rf
o r w h i te blood cel' ls. Accor dingto the Leukem ia
S o c i e t y , t h e r e a r e 7 0 , 0 0 0n e wc a s e so f l e u k e m i aa n d r e l e a t e d d i s e a s ei n
t h e U n i ted S ta te s e a chye a r and 4.|,000deaths.
I n t h i s a u t o l o g o u st r a n s p l a n t t e c h n i q u e ,t h e p a t i e n t , w h i l e i n
r e m i s s i o n , i s a n e sth e ti zeda nd one to two quar ts of bonem ar r owar e
e x t r a c t ed a n d p roce sse dto rem over ed blood cells. M onoclonalantibodie s ,
w h i c h a r e prod u ce dfrom l ab o r ator y m ice and act against specific pr otein s
'l e u ke mi a
o n t h e surface o f
ce' |1s, ar e addedfor an hour ; then baby r abbi t
s e r u m ,a so u rceo f compl ement,
is added.The two acting together destr oy
t h e l e u ke mi ace l l s, a p roce ssknownas m ar r owpur ging. The tr eated m ar row
is then frozenandstored in liquid nitrogen.
P a t ien ts th e n u n d e rgoa n aggr essivetr eatm entof high- dose
c h e m o t he rap thayn d w ho l e-bo dyir r adiation to destr oy r esidual Ieukem ia
c e l l s i n t h e i r b o d y . T h e n ,t h e c l e a n s e dm a r r o wi s i n f u s e d i n a n a t t e n r p t
t o r e g e ne rateth e p a ti en t's m ar r owwith nor m alcells, fr ee fr om disease.
T h e p a t i e n t i s s u p p o r t e dw i t h a n t i b i o t i c s a n d b l o o d t r a n s f u s i o n sf o r
s e v e r a l w ee ks,a fte r w hi ch th e tr ansplantedm ar r owbegins to function.
The treatment takes one to two months.
S o f a r , 2 2 p a t i e n t s h a v er e c e i v e dt h i s t r e a t m e n t ,i n c l u d i n g 1 6 w h o
w e r e i n comp'l e te
re mi ssi ona t the tim e of infusion and ther efor e had the
b e s t c h a n c ef o r a p o s i t i v e r e s p o n s e 0
. f t h e 1 3 p a t i e n t s i n s e c o n do r
t h i r d c o m p l e t er e m i s s i o n ,e i g h t o f l l p a t i e n t s w h oc o u l d b e e v a l u a t e da r e
s t i l l a l ive u p to 2 8 n ron th sa fter tr eatm ent,with a m edianfo]1ow- up
s u r v i v a l o f l 6 mo n th s.l .l i th standar dchem other apy,
the aver agelength of
s u r v i v a l f o l l o w i n g r e l a p s ei s f o u r t o f i v e m o n t h s .
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F e b .9 , l 9 B 7
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There are severa'ladvantagesto the autologoustransplant over the
a l l o g e n ei c p roce d u re,i n w h i c h the patient r eceives the bonem ar r owof a
b r o t h e r o r si ster. In th e tra ditional pr ocedur e,even thoughthe patient
a n d d o no r ti ssu e typ e s match, about thr ee- quar ter sof tr ansplant patients
s u f f e r a rea cti on kn o w na s g r aft- vs.- host disease, and a quar ter die fr om
i t o r f r o m i nfe cti on s a sso ciatedwith it. The diseaseis causedby donor
m a r r o wce l l s a tta cki ng the p atient.
T h e au to l og u sp roce d u realso m akestr eam entavailable to m or e
p a t i e n t s . E v e nw h e na b r o t h e r o r s i s t e r d o n o ri s a v a i ' l a b l e ,t h e d o n o r ' s
t i s s u e s m a t c ht h e p a t i e n t ' s i n o n l y o n e - f o u r t ho f c a s e s .A l s o , b e c a u s e
t h e r i s k a n d seve ri ty o f g raft- vs.- host diseaseincr easeswith age,
t r a d i t i o n a l a'l l og e n e i ctran sp' lantsar e not donein patients m or ethan 50
y e a r s o l d . S i n c e t h e r e i s n o r i s k o f t h e d i s e a s ei n t h e a u t o l o g o u s
p r o c e d ure,o l de r p a ti en ts ca n be tr eated.
A l t h o u g husi ng mon o cl onalantibodies to tr eat the m ar r owof
l y m p h o cyti cl e u ke mi ap a ti en ts has beendoneat var ious center s, including
w as the fir st' use the m ethodto tr eat acute
Sc r i p p s C l i n i c, D artmo u th
m y e l o g en o ul se u ke mi a .A si mi lar tr eatm entfor acute lym phoblastic
l e u k e m i a,the type ch i l d ren contr act, has beenused for som etim e.
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