nutritional therapy in children with cancer

8/8/2019 Nutritional Therapy in Children With Cancer

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[C A NC ER R E SE AR C H 3 7, 2 45 7-2 46 1 , J uly 1 97 7]

SummaryT he spe cia l b io lo gy an d be havior of the ch ild m ake nu tnition an even m ore im po rtan t a djunct to ca ncer the rapy tha nis true for the adult. The tim e has com e to add nutritionaltherapy routinely to our other m odes of therapy: surgery,radiotherapy, chem otherapy, and im munotherapy. B ut itshou ld be do ne in the sam e w ay o th er m od alitie s a re a dd ed ,i.e ., w ith c on tin ue d p ro sp ec tiv e a nd re tro sp ec tive re vie w o fthe data to optim ize the approach to the child.

IntroductionA t first glance the need of the child for optim al nutritionduring m anagem ent of cancer therapy appears to be nod iffe re nt fro m th e n ee d o f th e a du lt. A ll th e q ue stio ns ra ise dabout cancer therapy and optim al nutrition apply to thechild as webbas to the adult. The question of whether theprese nce of can ce r im po ses b arge m etab olic de ma nd s onthe host is ra ised in therapy w ith children as w ell as in thatw ith adults. The need for evaluating the possibility thath yp era lim e nta tio n e nh an ce s o r in hib its tu m or g ro wth n ee dsclinical e valuatio n in the ra py w ith ch ildre n as w ell a s in th atw ith adults. S ince the treatment of cancers in children ise sp ec ia lly d ep en de nt o n c he mo th era py , th e p oss ib ility th ato ptim al n utritio n w ill in cre as e to le ra nc e to c he mo th era py is

very im porta nt inde ed.A rtificial fo rm ula s fo r en han cin g g row th an d im pro vin gn utritio n in ch ild re n a re o f co urs e ve ry o ld . N or is p an en te ra bh yp en alim e nta tio n n ew in c hild c are . T he p io ne erin g s tu die so f D ud nic k e t a !. (3 ) w e re firs t a pp lie d to yo un g in fa nts . M an yof the studies of hyperalimentation in children have inc lu de d p atie nts w ith c an ce rs. C on ve rs ely , a mo ng s tu die s o fhyperalim entation in cancer patients there have alw aysbeen a few studies of hyperalim entation in children. It istherefore possib le to am ass studies from the literature todocum ent that optim al nutrition show s the sam e types ofben efits in child ren as it do es in a du lts. H ow ever, th ere arefew studies in w hich optim al nutrition therapy in childrenw ith can ce r is a sp ecific go al (5). H ow eve r, such p ub lish edexperiences, as well as my own, show that all considenatio ns fo r a du lts co nc ern in g d ie t, n utritio n, a nd c an ce r a pp lya s w ell to ch ild re n.N ev erth ele ss, th ere a re u niq ue fe atu re s in th e th era py o fc hild re n w ith c an ce r, w hic h th is p ap er w ill b rie fly re vie w.1 ) T he ty pe s o f ca nc ers s ee n in c hild re n a re d iffe re nt fro mth os e s ee n in a du lts , a nd th ere is a v as tly im pro ve d o utc om e

I Presented at the Conference on Nutrition and Cancer Therapy, Novemb er 2 9 to D ec em be r 1 , 1 97 6, K ey B is ca yn e, F la .

from cancer therapy w ith children than from that w ithadults.2) The continued grow th and development of the childd urin g c an ce r th era py is re qu ire d, n ot ju st m eta bo lic h om eostasis as in the adult. It has already been dem onstratedthat during gro wth a rtificia l feed in g h as b ee n p ossib le , b utthere is in addition a question of the relationship betw eenn utritio n a nd c og nitiv e d ev elo pm e nt.3 ) C h ild re n h av e u nfo rm e d y et s tro ng er fo od p re fe re nc es .T he re is a s pe cia l d em a nd fo r d ein stitu tio na biz atio n o f fo od .4) M alabsorption syndrom es are frequent and m ore S evere in children, w ith rapid onset in the very young ando fte n w ith fa ta l o utco me if n ot m ana ged p rom ptly.5) There are m any relationships betw een nutrition andim m un ity a s w e ll a s b etw ee n im m un ity a nd c an ce r. C hild re nw ith their unch alle nge d im mun e syste ms are m ore likely tob e hu rt by m aln utrition tha n a re a du lts.ImprovedOutlookof ChildhoodCancers

C ancers in childhood com prise a specia l group. N onhem ato lo gic al c an ce rs p re do min ate ; a pp ro xim ate ly 4 0% o f a llca ses are le ukem ia a nd an ad ditiona l 10 % are lym pho mas.Among the solid tum ors, brain tumors and other centralnervous system tum ors are next in frequency. Systemictu mo rs a re la rg ely sa rco ma s a nd n ot ca rcin om as . M ub tim od ab t he ra py a nd in te ns iv e c om bin atio n c he mo th era py h av em ade it possib le to show significant advances in the outcom e o f ch ildh ood can ce rs. T hus, th e actu al m ortality statis tic s o f c hild ho od c an ce r h av e c ha ng ed fro m 6 .5 /1 0 0,0 00in1969to 5.5/100,000n1973 (10).C a us es o f m o rta lity a re s till fre qu en tly th e c on se qu en ce so f d is ea se a nd th era py. B le ed in g a nd in fe ctio n a re s till h ig ho n th e lis t. H ow ev er, im pro ve d b lo od p ro du ct s up ple me ntatio n a nd im pro ve d a nti-in fe ctiv e m od alitie s h av e m ad e s uc hcom plica tio ns som ew ha t less threa ten in g th an the y w ereeve n a d ecad e ag o (1 6). It ap pe ars n ow tha t m alnu tritio n israpidly rep la cing th e fo rm er 2 as th e cau se o f m ortality.Table 1 sum marizes a typical exam ple of a patient whow as tre ate d for w ide ly disse mina ted ne urob la stom a, w itho nly o ra l a bim en ta tio n a s s up ple me nt. It is v ery c le an th at a llparam eters of m alnutrition appeared, including a decreased height/w eight ratio as w ell as a fall in serum album m. Tow ard the end the patient becam e unresponsive tofurther chem otherapy and expired. It is certa in that thepatient's death at beast in part w as due to m alnutrition.H ow ever, the lesson is not the phenom enon itself, but thefact that a physician allow ed this to happen because nep ea te d c alo ric c ou nts s ho we d a p ro ba bly a de qu ate ca lo ricin take (if the child ha d bee n n orm al and no t u nd er the stre ssof cancer and chem otherapy). Neunobbastom a may be

JULY 1977 2457

Nutritiona l Therapy in Ch ild ren with Cancer1Jan van EysD ep artm e nt o f P ed ia tr ic s, U niv ers ity o f T ex as S ys te m C an ce r C en te r, M . D . A nd er so n H os pita l a nd T um o r In st it ute , H ou sto n, T ex as 7 70 30


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Courseofnutr it ional state inprogressiveeuroblastomaSerumWeight/albu

heightmmg/DateWeightHeightrat iodl)Nutr it ionChemotherapyRadiotherapyClinicalstateOctober13.099.014.04.4OralfeedingVincrist ine-cytoxanAbdominal diseaseNovember13.899.513.9Oral feedingVincnistine-cytoxan-adria

mycinSkullMetastictokullDecemberOral

feedingVincristine-cytoxan-adriamycinRemissionJanuary

FebruaryMarchApril13.013.713.013.299.5

10 410 411113.113.212.511.94.5\

[email protected]@2.9ing,75 to 100Nasogastricfeedkcal/kg/day

IVH startedVincnist ine-cytoxan-adriamycinPhaselbchemotherapyP h as e I I c he m ot he ra pyPhaseII chemotherapyRadiotherapySupraclavicular

massDisseminat ionProgressionDeath

J. van E ysTa ble1

unique in that the catechobam ines often secreted by thetumor m ay actually create a catabolic state above and bey on d th at se en in o th er ca nc ers . N eve rth ele ss , th e in ab ilityof the physicians w ho cared for th is child to translate thea bn orm al s ta te in to th eir kn ow le dg e o f n utritio na l re qu irem ents resulted in in ade qu ate th erap y. It is th erefo re a bsob ute byc le ar th at th e n ew th re at o f m aln utritio n a s th e ca us eof death, in view of the optim istic therapeutic outlook forchild ren w ith can ce r, d em and s clo se atten tio n to the o ptim al m ode of child nutrition. C onstant im provem ent of scie ntific in qu iry in to o ur u nd ers ta nd in g o f m eta bo lic d is ea seis n ec ess ary . U nfo rtu na te ly , it h as b ee n d em on stra te d o ve rand over again that nutritional education is often sadlyla ck in g in m an y m ed ic al sc ho ols a nd , e ve n w he n p re se nt, isnot taken as seriously by the students as one would hope(9). If indeed w e have an even-im proving outcom e for ourchildren,hen itbecomes even more importantthatourtre atm e nt b e w ith c ura tiv e in te nt. T his in clu de s a ntic ip atio no f n utritio na l co mp lic atio ns ra th er th an ju st re pa ir o f ia trogen ic and d isease- rebated malnu tr it ion .It m ight be m ention ed h ere tha t m arg in al m alnu tritio n isv ery d iffic ult to d ia gn os e. T his is e sp ec ia lly tru e in ch ild re nin w hom gro wth a nd de ve lo pm en t result in rap id ch ang es inre la tiv e n u tn itio na l re se rv es , a lth ou gh q ua lita tiv e re qu irem ents m ight be different as w ell. In childhood the mostnotable exam ple is the phenom enon of vitam in E deficiency, w hich is seen in adults only after very severe andp ro lo ng ed lip id m ab ab so rp tio n (1 ) b ut w hich is n ow a n ec ognizedsyndrome innewborns (11).

Growthand DevelopmentP ediatric ca ncers a re n ow alm ost inva riab ly ch ro nic d iseases. Even for those children for w hom the ultim ate outcom e is d ea th, the dise ase o fte n sp ans ye ars. T he re fore , itis alm ost im possible to predict the outcom e at the beginn in g of th e trea tm ent. P aren ts and ch ildre n ha ve to rem ainin u nc erta in ty fo r m an y y ea rs . D urin g th os e y ea rs th e ch ildw ill deve lo p a nd gro w. Line ar g row th ca n occur in spite o f ala ck o f w eig ht g ain (T ab le 1 ). M ore im po rta ntly , h ow ev er, isth e q ue stio n o f d ev elo pm en t. T he 3 -ye ar-o ld w ho is tre ate dfor 4 yea rs w ould be p hysically 7 yea rs o ld a t t he e nd of tha ttim e bu t, if no t a llow ed to de velop n orm ally, w ould still b e 3

m en ta lly . T his w ou ld h av e a d ev as ta tin g e ffe ct o n th e c hildand w ould result in an alm ost Incurable handicap even if ab io lo gic al c ure w ere a ch ie ve d. T his d ev elo pm en t d ep en dsof course to a very large degree on the attitude and theenvironm ent that adults make for the child during his illn es s. B ut if d urin g h is illn es s n o a tte ntio n is g ive n to o ptim aln utrition, o ne m ust ra ise the ob vio us qu estion o f the inte rre la tio ns hip o f c og nitiv e d ev elo pm e nt a nd m a ln utritio n.T he are a of n utrition de ve lo pm en t an d socia l be ha vior iso f c ou rs e a v ery c on tro ve rsia l s ub je ct. T his is n ot th e tim e o rp la ce to g o in to a le ng th y d is cu ss io n o f th e v ario us re se arc hd ata th at a re a va ila ble . T he c on fe re nc e o n th e a ss ess me ntof te sts o f beh avior from stu dies of nutrition in th e W esternh em isph ere , w hich w as he ld in 19 70 , sum ma rizes m uch ofthe da ta very w ell ind ee d (7). S uch studies, w hen no t usinganim al experim ents, a lm ost alw ays apply to populationg ro up s. T his is fa r re mo ve d fro m th e p erfo rm an ce o f a g iv ench ild. F urth erm ore, there is n o d ou bt th at the intelle ctua lperform ance of a child depends partially on genetics andp artia lly o n e nv iro nm en t a nd th at th e e nv iro nm en ta l p art isa t b est n ot e ntire ly th e n utritio na l in ad eq ua cy o n a de qu ac yo f th e p atie nt's d ie t. M a ny re vie w s s tre ss th e in se pa ra bilityof socia l environm ent and nutrition in fie ld studies andthe refo re the o ve rriding e ffe ct o f en viron me nt o ve r that o fn utritio n (6 , 8 ). H ow eve r, e ve n m in or e ffe cts h ave a h ab it o fbeing magnified if additional insults are occurring. Thec om bin atio n o f c he mo th era py, a rtificia l e nviro nm en t, u nusual parental attitudes, and prediction of m orta lity hasch ang ed th e en viron me nt of the child to such a deg ree th atw ha teve r add itio nal n utrition al insults m ig ht occur cou ldw ell b e g ro ss ly m ag nifie d. In p op ula tio n s tu die s th e s ep aratio n o f m aln utritio n fro m s oc ia l e nv iro nm en t is n ot p oss ib le .A child w ith cancer is likew ise a socia l subclass treateddistin ctly from th e p op ulation a t ba rg e. It w ou ld be trag ic,espe cia lly in th e ve ry yo un g, if th is a spe ct w ere fo rg ottenand no stud ie s w ere intiated to de ve lo p d ata in th is grou p o fpatients.Much of the literature on parenteral abim entation hascom e from the trea tm en t of prem ature a nd sick bu t m atu rein fa nts w ho h av e s uffe re d fro m v ario us fo rm s o f m ala bs orption O r th e inab ility to ta ke in ade qu ate nutrien ts p .o. F ro msuch studies it is abundantly clear that norm al grow th ispossib le (3, 4) and that the developm ental outcom e of thechild is at lea st n ot a priori d eficie nt (3). H ow ever, it is also2458 C AN C ER R ESEAR C HVO L . 3 7


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TableCompositionof parenteralalimentat ionolutionForperipheral hyperalim entation at 30 m I/kg/day, 10%ntralipidisgiven up to 500 mI/day. W hen that is done theyperalimentationsolutionis adjustedto Freamine(13g/I iter; 1.3%)and dextrose100g/Iiter;10% ), w hich results in a lowered phosphorus content to45mg/liter.A ll other com ponents are the sam e. Intralipid is usednceweeklyin al l pat ientswith the adjustedhyperalimentat ionolution.Afterthe 1st liter of this solution, the balance of the 24-hreriodusesa solution of Freamine II (15 g; 1 .5%), dextrose (200 g;0%),andsodium (aschloride) (1.75Eq).Component

Amount/ l i terFreamineII 15 g1.5%)Dextrose0 200 g20%)Sodium0 1.75EqPotassium(as phosphate)0 4.4EqCalcium(asgluconate) 400gPhosphorus 15 5gMagnesium(as sulfate) 11.4EqZinc(as sulfate) 0.8gCopper(assulfate) 0.4gFluoride(as sodium salt) 20gIodide(as sodium salt) 118gManganese(as sulfate) 0.4gM .V. I. concentrate 2lVitaminK 0.2gFolicacid 1 .0gVitaminB,2 5 /Lg

J. van E ysis he d h av e a h ig he r in cid en ce o f in fe ctio n (1 3). In a dd itio n,m alnourished children often have thym ic aplasia and decrease d effe ctive ness of the va rio us lim bs of th e im mun es ys te m (1 4). H o we ve r, th is d oe s n ot n ec es sa rily e qu ate w ithe ffe ctive im mun e supp ressio n. T he re la tio nsh ip be tw eenim m un ity a nd th e c ou rs e o f c an ce r is e qu ally in co mp le te lyd efine d a t this tim e. T he results fro m expe rim en tal tu morm od els s ug ge st th at u nd er p ro pe rly c on tro lle d c on ditio nsspe cific dieta ry m anipu la tio ns can restrict tum or g ro wth .But there is a m ore pragm atic re lationship. There is nod ou bt th at im mune su pp re ssion o ccu rs during m ost o f o urm od ality o f c an ce r th era py . In a dd itio n, if m aln utritio n w ereto be pre se nt, th e com bina tio n, w he the r ad ditive o n syne ng istic, n everth eless w ould result in a m uch in cre ased su sceptibility of the host to infection and, consequently, apotentially fatal outcom e in spite of a biological successw ith tu m or th era py .PracticalProblemsStillEncountered

T here still a re practica l pro blem s in the d evelop me nt o fo ptim al n utritio na l s up po rt o f th e c an ce r p atie nt. F irs t, th eo ptim al tim e fo r in sis tin g o n p are nte ra b o r fo rc ed h yp era limentation by other routes in the course of the patient'sm an ag em en t is s till u nc erta in . A n a na lo gy b etw ee n c he moth erap y a nd nutrition al th erap y m igh t be m ade . In chem otherapy the 1st step w as the developm ent of an anm am enta nium of effective d ru gs th at cou ld be used to p alliate th elife o f p atien ts w ith re cu rre nt or p ro gre ssive tu mo r. O ncesuch drugs were found to be successful, there was thep rin cip le o f c om b in atio n c he m oth era py th at d em o ns tra te dth e p ossib ility of a dding to gethe r the effectivene ss of 5 eve na l d ru gs w hile in de pe nd en t to xic itie s a llo we d n ea n-cu rative regim ens. A fter that princip le w as discovered, it bec am e p oss ib le to s ta rt a dju va nt ch em oth era py . T his m ea nsthat the treatm ent of m icroscopic and residual diseasescouldbe initiatedithcurativentent.S ec on d, n utritio n is s uffic ie ntly e sta blis he d s o th at v ig orou s nutrition al reh ab ilitation , p rim arily throu gh the use o fp are nte na l h yp era lim en ta tio n, a llo ws th e s alv ag in g o f p atients w ho are in severe stra its. This is so clearly the caseth at it is c on sid ere d u ne th ic al to u se m a ln ou ris he d c hild re na s s ub je cts fo r th e in ve stig atio n o f e ffe ctiv en es s, a s w ell a sfo r th e h arm fu l o n b en efic ia l e ffe cts o f p are nte na l h yp en alim en ta tio n in c hild re n w ith ca nc ers . T he c urre nt d ie t, n utn ition, and cancer program has a contract under which thedefinition of m alnutrition is a w eight/height ratio of lessthan 80% of the median according to data recently publis he d in c ha rts fro m th e H ea lth R es ou rce s A dm in is tra tio ne xam in ation su rve y (1 2). T his w ould includ e as m alno unished a num ber of patients w ho by m any standards w ouldo nly be m arg in ally u nde rno urish ed, a nd this also dem ons tra te s 2 p oin ts : (a ) m arg in al m aln utritio n is v ery d iffic ult todefine; (b) nutritional rehabilita tion is considered suffic ie ntly e sta blis he d th at it w o uld b e u nre as on ab le to d ep riv echild ren w ith even m argina l m alnu trition of its be ne ficiale ffe cts in la te s ta ge s o f c an ce r th era py .It is now im portant to bring the princip le of nutritionalc an e i nto th e s ta ge o f a dju va nt th era py . H ow ev er, a ra tio na ldesign of adjuvant therapy requires the defin ition of m ar

g in al m alnu tritio n as w ell a s th e d efinitio n o f optim al nu tritio n in p atien ts w ho a re being tre ated w ith the usua l therapeutic modalities. There are at present no data on thes pe cific c lin ic al-p ath olo gica l d era ng em en ts g en era te d b ytu mo r v ers us th os e g en era te d b y n utritio na l d eficie nc ie s.T he in te rre la tio ns hip b etw e en o ptim a l n utritio n a nd c he m oth era pe utic e ffe ctiv en es s is u nce rta in . A ga in , th e c urre ntd ie t, nutrition , an d cance r p rog ra m ha s b egu n to study thisis su e th ro ug h a c on tra ctu al co op era tiv e tria l th at a tte mp tsto id en tify in ch ild re n w ith a bd om in al irra dia tio n a nd ch emo th e na py th e e ffe ct o f e a rl y p a re n te ra b h yp e na b im e nta ti on .In addition, the contribution of optim al nutrition to there sp on se to h ig h-d ose m eth otre xa te a nd o th er c he mo th era py in m eta sta tic b on e tu mo rs is u nd er in ve stig atio n. H ig hd ose m eth otn ex ate is e sp ec ia lly p ro ne to g astro in te stin aldenuding if infusion is prolonged or beukovonin rescue isnot m ainta ined long enough. The nutritional support is byp an en te na ba bim e nta tio n. T he c om p os itio n o f th e s olu tio nsused in these program s are given in Table 3. This is anad aptation a nd com po site of so lu tion s used b y the pa rticipat ing insti tut ions.Promisesand Dangersof Nutrit ionalTherapy

It often happens that a conceptually attractive m ode ofth era py b ec om e s e ntre nc he d b efo re th e in dic atio ns , lim itatio ns , a nd o ptim al u sa ge h av e b eco me e sta blish ed . A cla ssic al c urre nt e xa mp le is h om e th era py fo r p atie nts w ith h emophilia, a therapy in w hich the habit is so entrenched thatthe re is little h op e tha t a pro sp ective stud y o f the o utco meo f s uch th era py ca n e ve r b e m ad e (17 ). N utritio na l th era py isin danger of going that route also. There is no doubt thatn utritiona l re ha bilita tio n ca n be life savin g. B ut w e sho uldn ot be b lind to ou r ign oran ce in nutrition al d ia gn osis in the

a Sodium and potassium are adjusted according to needs.

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N utritio na l T he ra py in C hild re n w ith C an ce rpatient w ith cancer. N or should we ignore our lack of und ersta nd in g o f th e co mp le x in te rre la tio ns hip s b etw ee n th eeffect of cancer on the host, nutrient metabolism , andc he m o th e ra pe u ti c e ffe c ts .O n the o the r h an d the fu ll po ten tial of nu trition al thera pyis n ot n ecessarily realize d. N utritio nal m an ip ulation h as apotentia l of affecting tum or grow th in w ays that m ay givedirect e ffects on th e tum or o r m ay alter the susceptib ility o fthe tum or to chem otherapy and radiotherapy. The area ofe ne rg y m eta bo lis m o f tu mo r tiss ue a s a p oin t o f th era pe utica tta ck is la rg ely u nu se d (1 5).

References1 . D arby, W . J. T ocopherol-responsive A nem ias in M an. Vitam ins H orm o ne s, 2 6: 6 85 -6 99 , 1 96 8.2 . D on ald so n, S . 5., J un dt, S ., R ic ou r, C ., S arra zin , D ., L ew erle , J ., a ndS c hw e is gu th , 0 . R a dia tio n E n te rit is in C h ild re n. A R e tr os pe ct iv e R e vie w ,C lin ic op ath olo gic C orre la tio n a nd D ie ta ry M a na ge me nt. C an ce r, 3 5:1167 -1177 , 1975 .3 . D ud ric k, 5 . J ., W ilm ore , D . W . , V ars , H . M ., a nd R ho ad s, J . E . L on g-t ermT o ta l P a re nt er al N u tr it io n w it h G ro w th , D e ve lo pm e nt a nd P o sit iv e N it rog en B al an ce . S ur ge ry , 6 4: 1 34 -1 42 , 1 96 8.4 . F iller, A . M ., E ra klis , A . J ., a nd D as , J . B . T ota l P are nte ral N utrit io n inP e di at ri cs . R a tio na le a nd C li nic al E x pe ri en ce . I n: H . G h ad im i ( ed ), T o ta lP ar en te ra l N ut ritio n, P re m is es a nd P ro m is es , p p. 4 45 -4 82 . N ew Y ork :J oh n W ile y & S on s, In c. , 1 97 5.

5 . F ille r, R ., a nd J aff e, N . S up po rt w ith T ota l P are nte ra l N utritio n (T PN ) inC hild ho od M a lig na nc y. P ro c. A m . A ss oc . C an ce r R es ., 1 7: 1 40 , 1 97 6.6 . F om on , S . J . In fa nt N utrit io n, E d. 2 , p p. 5 08 5 14 .P hila de lp hia : W . B .S au nd er sC o ., 1 97 4.7. Kallar, D. J. (ad.) Nutrition, Developm ent and Social Betiavior. In: U. 5.D e pa rt m en t o f H e al th , E d uc at io n, a nd W e lf ar e P ub li ca ti on ( NI H) 7 3- 24 2.W a sh in gt on , D . C .: U .S . D ep ar tm en t o f H ea lth , E du ca tio n, a nd W e lfa re ,1973.8 . L ev in e, S . , a n d W ie ne r, S . A C rit ic al A na ly sis o f D ata o n M aln utritio n a ndB e ha vi or al D e fi cit s. A d va n. P e di at ., 2 2: 1 13 -1 36 , 1 97 6.9 . M oo re , M . E . N utritio n E du ca tio n in M ed ic al S ch oo ls . U pd ate 1 97 4. In :w. j. Darby ad.),TheApplicationof Nutrit ionntheH ealthScienc es,p.6 -1 3. W a sh in gt on , D . C .: T he N ut ritio n F ou nd atio n, 1 97 4.1 0. M ott , M . G ., W ilb ur, J . R ., a nd S uto w, W . W . T he C ha ng in g P ro gn os is f orC hild ho od M alig na nc y: a Q uie t R ev olu tio n. L an ce t, in p re ss .1 1 . N ath an , D . G ., a nd O sk i, F . A . H em at olo gy o f I nfa nc y a nd C hild ho od , p p.1 35 -1 38 . P h il ad elp hi a: W . B . S a un de rs C o ., 1 97 4.12. N ational C enter for H ealth S tatistics: N CH S G row th C harts, 1976.M o nth ly V ita l S ta tis tic s R ep or t 2 5, N o. 3 . S up pl. ( HR A) 7 6-1 12 0. R oc ky ule , M d . : H e al th R e so ur ce s A d mi nis tr at io n, 1 97 6.13. Scrim shaw, N . S., Taylor, C. E., and G ordon, J. E. Interactions ofN utrit io n a nd In fe ctio n. In : W HO M on og ra ph S erie s, N o. 5 7. G en ev a:WHO,1968.1 4. S m y th e, P . M . , S til es , G . C ., a nd G ra ce , H . J . T h ym o ly m ph at ic D e fi cie nc ya nd D e pr es sio n o f C e ll- m ed ia te d I mm u nit y i n P ro te in -C a lo rie M a ln ut rit io n. L an ce t, 2 : 9 39 -9 43 , 1 97 1.1 5. v an E ys , J . C ellu la r M eta bo lis m a nd E nv iro nm en t. M ol. C ellu la r B loc he m ., 8 : 4 3-4 8, 1 97 5.1 6. v an E ys , J . S up po rt iv e C are fo rt he C hild w ith C an ce r. P ed ia t. C Iin . N orthA m ., 2 3: 2 15 -2 24 , 1 97 6.17. v an E ys, J. H om e T herapy for H em ophilia. In: M . W . H ilgartnar (ed.)1H em op hilia in C hild re n, p p. 1 85 -2 00 . L it tle to n, M as s.: P ub lis hin g S cie nc es G ro up , 1 97 6.

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nutritional therapy in children with cancer

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