Blood Changes in Humans Following Total Body Irradiation

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A mjor problem facing the Manhattan Project u a a * the proteotlon of workers qa in st damage re eu lt ix iron either acute or chronla sxpoaum to external radiatfon, dose sustained by pereonno1 and the rate of administration could damage, either transitory or permanent, uhioh night arlse from auoh I t uas anticipated that the total Further, there was t h e problem of ksseaelng tb0 Tbe problem or detectfw evidence of damw follooring exposum to total body radiation led to thle studg. evidence point cd to the blood-forming orgrine 88 some of the moat radios'ensitive tissues In the body. men thle study maa undertaken, the work prevlouoly done on this uubjeot Indicated that cbange8 In, the blood-forrr,ing organa and i n the horntological o on at ltu ents of the per lp he ml blood were a Rood index of erpoaure of the whole body tor adl ~ tlon, whotlior chronic as aeon In ocouptional exposum( 6)W or acute 88in radiation therapy (9)(lO)* me respomes or this system Can be rehdlly, although indirectly inferred bp aerial determinations of the absolute numbom and rat loo of the var low cellular alemente of the blood. peripheral blood and reported i n the literature a r e epiwdwd in The major chan&ea observed In the

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d ter acute exjJosure t o larce amounts of radiation, a prsc ip ltu te fell had been noted inthe absolute number of lymphOCYW8 togs the r with8transient,m rke d increase in the number of neu tr ophile s, folloived by n morked decrease in their numbers. The tins neceusary I'OT tho return to noma1 of both lymphocyte8 end of red if it ion rcceivod by the subject. Depression8 in the number was nota c3xRtent find iw. cells end in the anourit o r hemoglobin we,re not usually noted. Alterations in the number of red blood After ex-msure t o chronic (occupational)radiation,the number crsnsed. The nucrber of neutrophiles was cornonly said to be decreased. Incroese of t h e number of' rr.onocytes has bgen described. Thus, although the total white blood cell count could be within the norm1xrde,there lh ti ve nunbers of the vo riou olen ents might vary rnrkedljr. Alter et ions in tho hemglobin value orin the nut or of rod blood cells and platelets wore usually described no o. relatively lute msult of yorsistent cxposum t o low levels of Bocause of t h o depondence which m a belnl; placod on certaln.persia tent dovietions of tho elenents inthe peripheral blood,It seemed I12)(13) .expedient tore investigate in man, both horn and elsewhere the effects of total body radiation,

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Three goueml grouyo are.used for the prsone who were subjected tore diet ion duriw this study. persons who hhd neoplasms which could not be cured but z till w ro The tirot group consietcC'of eight not extensive enough t o Influence eenernl health.. given tote1 body ir rad ln tion In single exposurea, with dosee of 27, lllnesscs xfiicl; :wre genorelized and chronic In nature. This group was Tho second group o on s is ted of three persons who had elver. tstnl body lr rad ln ticn In nul tip le exposures, with total dosss of 103, 300, and 500, Insofar as Is known, they had no ab nom ll ties. given tots1 body lr ra dlc tion In three divided doses to a total of The third group consisted of three This group was __chborebtor-yF zm imt ions. The choneee In the poripheral blood cells woro Rtu.diod. Tho tecltn included detornSnation of t h e homo- ~ l.obi ni n &f-; hm a to crit in c c per 100 cc; numbera ofred blood cella, white blood cells and platelet8 per m3; and est lm tl on of the number and percentaee of tbe varloue elements of the white blood cells. differential KO8 commonly baeed on 500 cells. The n o m 1 values for this laboratory are given i n Chapter IV of this volume.

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bioclienical studies on blood, urlno, and feces were alno performed. These will bo reported in ds toll a'lnewhore In this aeries (Schwartz, Vole 20-l), I n ons cnso s arial bono mnrrom biopsies b'ere pr fo me ao the treatment boini: given with tho priticnt seated in a light wooden ct'air with either the right or lert side of thc body toward the x-ray tube.All of the body, oxcept the feet, was Included In the field o The dose was measuroti by L), Victoreen fntegron, checked I n each in sten ce by deter.-dnations with a Victoraer. r rnoter, usiw a 25 r ionize tion ctar,ber. The ionize tion ch mb or xa8 placed i n the breast pocket or the pEt ieC to s dree s iw gown. The p - t lent s in the second md third groups ' ve retreated with 200 KV x-rays th mag k sonemhat om ll or fields. Two fields worn used anterior ly ond t xo posterior ly to cover the entire pcrson while lying down. "lie doso given t o e2ch of the tno fields was considered a8 the dose t o tke whole body. .In Grout' two, the treatrsent was Biven In fron 2to 30 dayern I . In cul cu latins tlio dose o&.inistored t o tho put i cnt s In emups ' two und three thou rou nt recolved by the nn teri or surface waa added t o thot received by the posterior surface and ivaa called the *total body expaurem. For example, exposure of each of the anterior and posterior fields to 20 rWR ~I nter pre ted as an exposure of the patient to 40 rrn #'e are amre Ll ibt this ie contrury to usual clinical practice, but felt

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just if lod In uolnt : 60 Locouse the worker exposed t o occuyutional radiation my receiver adl ntl on from a:iy direction, but usually only from orre direction at8tine. Hie naximum permissible level of eXp03UE is not 100 mr t o each body surface, but a total of LOO mrto oll 3urfaceso to the ants rim ~ n d.prJterior body surf n ces scer.6 to best approxiConsequently, th on dd it ion of the doses rite the s it unti on of the worker. A 53-peer old white mle \ alth carcinoma of tke ep16lottis and extensive bil c ter ol cervical metastases was reerowtb of the cor vlc ally qh rides showod his outlook t o be. hopelease Therofore, on Ilarct 13 1343 he 1 ~ a 3Ijiven a t o t a l body exposure of 60 re Flgura 1 &rid Table IX show the he cato log l cal responso. ! b y show that the. ~ li it G blood coll count dropped imcdlcitelg followin(: the trop.tmcnt, tho do crease belnp, transient. The.major effect of tho trCQtment was found t o be on t h e lyzphocytes which decreased in number immedie tely f0110W1,~t he tre a tmnt, the reduced level perslating throughout th s 157 d:iys of observation. The elements of the blood did not shov my alterations v:hlch wore attributed to the effects of the

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Figure l J Casu I Reepnses o r blood elexents following a elngle exposure oi the er.tlm body

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a carcinoma in vol v irq the ri.Th t tonsil lar pilltir and foesa, the tnoen Decc:r;ber, 3342 azd Februcry, 1943, 7200 r throw h D. single gene nil conditioz ws fair but resp on m to tre a tmnt EhVi:ed that cure ws not to be expoctod, A to tul body exposure t o 60r pa8 Tr,o results ci' thi hosatoloSico1 studies are to b found The duration of the increase wa8 only t few hours. The lymphocytic values ln cree scd for3 hours and then roll below tho initial level, tho decrease p3rsistir.g throw h out the 151 drlys of observation. ??le pl n te lot count droppcd nodcrrttoly from the29th to tho 71st day. The other elen ents of the blood studied did not show any a i ~ nlf i cent Case III, A 59-goar old akite male1 was found in D,,.cont.er, 1942, t o 1itivc 8.qua nous. cell carcinoxn of the epic lot tls, tyus Given d url nc Jariuury, 1343. On April 17, 1943 t h e primary lesion stl.11' yroseiit olthouCh reuuccd :n ciao On that date 60 r Of totel body rti diet lon WAS r,lvan,

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Figure 2, Case I 1 : ~ e op nse ao f blood elaraente rolioRqng a e1ry;le expcsure of the entire body t o 60 re

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The total v:lqite blood cell cour't decreunetl dur irq the first few fi can to lter il tion wus seen. tothe erfects ortho rud.:btion exposure. " t o lymphocytic values decroosed The valucs returns d ' 140 o th s rab no rcE Ji ties xore attributed irr Ja:iu:..T;', 1942, of a mtiss in the right bron st for thc pfi3t unco z troi icd, hnt no other cet astn ses vrore noted and her eenerfil 17-10r es u lts of the hcrintolo[;:..csl stubier; ore civ en in Table V cyte sint,h Cc irc ul uti x blood is shc:m. No o thor effect of tho ox is sure is men.'.. Tho incretlse i n nuqbor o f .white blood celle on the56thund 154th doys rim assoclattrd with u cute upper respiratory

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Figure.3, Sase 111 Reslonsss o r blood elements iollowiag a sinele 6xyosure of the entire body

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Case V, A white mele \ , aged 57, shoved IL October, 1942 an advanced carcinoma of tho e pig lot tle involving the left Eubwere noted subsequently In the C eml ce iq mp nodes, \;TIS done In Ap-11, 1942, On JUO 4, 1343, 27 r totKL body radiation was given. lIin eonern1 condition at that tine vas good. In thet month, 6500 r WUB given to the left cervical "ke results of the 10!%itOlOgIC3lstudies are given I n Table V I following the tres tx st 3cci a slight leuk o cyto s is Is noted throw h - carcinoma of the left kezilaryw with fixation of the 1~rynx. Duri3i : January and FdbrJc;ry, 1933, 4050 r we6 given totho lesion t:irough a six le field. Cn Jur.0 26, 1943:120 r total body rud in tion CIvB.?r. KRS uncontrolled a ttl it it tira. The results of the hone to logical studis3 ere given In T aSh VI1 and Figure 6, The 24 and 48 hour pl n tel ct cour.ts are de2r6060d. The. pre - radio tion value. Case VII. A 65-;roer old white male \ was f o u d $0 bavo a however. On Au zx Jt 28, 15'43, 120- r total body redietion was given.

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~ 1 ~ 1 5exposure of the entire body to 27 re

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E'1g~i1-06. Case VL ir Reriponses of blood elcmenta following a single exposure ot the entire body to.120 re

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The general condition :re8 fair et the time of th a exp sure. The la ry nge nl lo:,ion was infected. nunber of ricritrophilss !as proson'; throw h out the porlod of obLeukocytosis due t o an c ? lem tion In the' count was very lovr on, the'.j!j>;h d:ly, A dscrorise in tho numbers of red blood nuqll ~;ind I n mo:iut of hmo ~ lohi nis noted. Cose VLII. A 54-year old tvhlte mole fir;t ;Ben in Tho pletelet count:, frcm the secotd t o the fourteonCk. Arncth counts v:ers done also on other cm es in GrouJ) f He ma given 502 r total body mC in tion in six tre%tZontS betV:een

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Fimm 7 . Case VI1a Responses of blood elements following (i 81rqle exposure c it fie entire body t o 120 r,

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39Tho first cind oecond tree tn ents viers eivun on h'ovenber 26 -and 27, and the third to the sixth treatments were given on Tr an a ien tna u ~ o aand vomiting were noted after tho first trm treatment8 a d sguln uf tert hu sixth. 'Bectone of the condition of the patient (see Pigum 9), 3750 cc of citrate d whole blood condition was poor for one iccek sf ter the completion of the treat - ments. The clinical rucovery vmo prececied by an increase in the white blood cell love ls, The henetoloCics1 dcta a r e presorted in Table XI and Figure 9. The totel white blood cell count w s so:mwk.nt depressed by the first two tr qat rie nts,the general level fnllinr; by about 2,533 cells ' per mm A profoud effect Y&S noted follow in q the third and subsequent treat - ments; the to tul white hlood celi count dropped s tend i ly from the 18th day tothe 31st day at which tine It rcacliod a low of 350. The polymorphonucleur cell relrctions closely pr allele dtl ir rt of the total white blood cell count. numbers after the tlrst tno treatments and did not ayprcach t o prera diet lon levels until the 53th day after therapy m s begun. blood elements Studied,the lyraptocytos were affected the earliest Tno lyl.,phocytes wcro m rke d ly reduced i n rheunntoid arthritis s ln ce ' 1941. h'o yrovious radirition therapy i e Total body Ir mdl uti on to (i toto1 of 300 r was given in 33 days In October and a n d Kovomber, 1944. the d is esse was fioted durin z cr after the treat n ents. No ranrked change in t h e course of