syndrome of inappropriate anti diuretic hormone secretion complicated with stem cell transplantation

8/2/2019 Syndrome of Inappropriate Anti Diuretic Hormone Secretion Complicated With Stem Cell Transplantation

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Syndrome of Inappropriate Antidiuretic HormoneSecretion Complicated withStem Cell Transplantation

Ryoji Kobayashi M.D., Ph.D.Department of Pediatrics, Sapporo Hokuyu Hospital

Key words: hyponatremia, SIADH, CBT, stem cell

transplantation

Correspondence: Ryoji Kobayashi M.D., Ph.D., Department of Pediatrics, Sapporo Hokuyu Hospital,Higashi-Sapporo 6-6, Shiroishiku Sapporo, 003-0006, JapanTel: +81-11-865-0111, Fax: +81-11-865-9719, E-mail: [email protected]

Summary

Hyponatremia is a common electrolyte disorders inhospitalized patients. However, reports about hyponatremia

complicated with stem cell transplantation (SCT) were very

rare. As single center analysis, syndrome o inappropriate

secretion o antidiuretic hormone (SIADH) ater stem cell

transplantation were reported. SIADH were observed 13.2%o 197 patients ater stem cell transplantation. Risk actors

or SIADH were younger in age, transplantation rom HLA

mismatched or unrelated donor, cord blood transplantation, and

GVHD prophylaxis with methyl prednisolone. Multivariate

analysis showed transplantation rom alternative donorwas independent o other actors or SIADH. Patients with

SIADH had signifcantly higher probability o overall survival(66.4% versus 50.8%) and event ree survival (68.8% versus

43.3%) compared with no SIADH. The median onset oSIADH ollowing cord blood transplantation (CBT) and bone

marrow transplantation (BMT) / peripheral blood stem cell

transplantation (PBSCT) was 19.5 and 46 days ater SCT,respectively, and the median numbers o WBC were 1.1 and

3.3 x 109 /l, respectively. Furthermore, severe symptoms such

as seizures, somnolence, and rigidity o limbs were observed

only in patients with CBSCT (8/16 versus 0/10). These

dierences were statistically signifcant (P


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240Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 8, No. 4, October 2009

spli ws lws qi. Hpi is

ll isb ig p 15% hspiliz pis hs b xsivl viw.1-3

Hwv, ps b hpi pli

wih s ll spli w v .4, 5 W

pvisl p hpi, spill s ipppi si iii h(SIadH), pli wih s ll spli.6

I ii, w pvisl lz il

lg b pis wih SIadH llwig Sct,

i SIadH liil s llwig cBt

Bmt/PBSct.7 I his pp, I lz pis wihSIadH llwig Sct sig w spl h

his SIadH pli Sct.

PatIentS and metHodS

Bw Fb 1988 mh 2007, l

197 pis wih i hlgil ligis,bli bll ii iv

Sct i Hkki ivsi hspil. o h

w v pis w b sv-w pisw gils. Six-w pis h lphblsi

lki (aLL): 30 h w i hi s pl

issi (cr), 21 w i s cr 11 w

v hi cr. thi-h pis w

lgs lki (amL): 17 w i hi s cr,11 w i hi s cr 5 w v hi cr.

o h w pis h h isss: 29 w

plsi i (aa), 12 w bls, 10 w

-Hgkis lph (nHL), 8 w lsplsi

s (mdS), 8 w jvil lilki (JmmL), 7 w hbs, 6 w

hi lgs lki (cmL), 5 w Wisk

alih s (WaS), 3 w sv bi

ii, 3 w Ks s, 2 w

Hl s, 2 w hi gls iss,1 ws lk s , hpbls, H s,

X lik hp Igm s, piiiv l

(Pnet) hi iv epsi-B vis ii

(caeBV) Hl Shi s, spivl.

oigis s ll w 122 pis wih b w

spli (Bmt), 25 pis wih piphl bls ll spli (PBSct), 4 pis wih Bmt

PBSct 46 pis wih bl s ll

spli (cBt). d spli w 61

wih HLa h sibligs, 3 wih 1 ls ishsiblig, 2 wih 3 li ish siblig, 12 wih HLa

h ish ps, 48 wih HLa h

l s, 34 wih HLa 1 ls ish

l s, 4 wih 2 li ish l

33 wih spli. th iiig

gi s i 69 pis bsl (Bu) iig

gis, 93 wih l b iii (tBI) iiggis, 57 wih lphl iig gis, 125

wih lphsphi (cy) iig gis

43 wih i lph glbli (aLG) iig

gis. Pphlxis g vss hs iss(GVHd) w 71 pis wih lspi a sh hx, 3 pis wih lspli a l,

42 pis wih lspi a hl pisl,

32 pis wih lis sh hx,

10 pis wih hx l 1 pi wih

lis hl pisl. d ws lzs apil 1, 2008.

eVaLuatIon oF HyPonatremIa

Vl s si ws s wih . a ig ws k il v Sct

pi il 40 Sct. W hpis ss wih i lss h 130 l p li

s si i siv s. Fh, w

s sv hpi s ss wih i lss h125 l p li s si i siv s.

dIaGnoSIS oF Syndrome oFInaPProPrIate antIdIuretIcHormone SecretIon (SIadH)

SIadH ws igs wih ii p b B

Shwz,8 whih qi h ps ll h

llwig: 1) hpi wih hpii pls;

2) i slli i xss pls slli;3) is l si xi; 4) bs

vl pli; 5) l l l

i.

StatIStIcaL anaLySIS

a t s hi sqi s ws s p pis

wih SIadH SIadH. alss vll svivl

v svivl w p sig h Kpl

mi h wih is p b h lg-

k s. mlivi lsis spwis gssi ws

p xpl h ip viblsh shw sigi if b ivi

lsis. Sisil lss w p sig d.

SPSS II wiws (ls 11.0.1J, SPSS JaPan I.).

reSuLtS

SIadH ws 26 (13.2%) 197 pis.

Pl pis vl tbl 1. cBt ws g

i 16 pis, spli ish

Ryoji Kobayashi

pp 239-245


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Ryoji Kobayashi

Table 3 Risk factor of SIADH with multivariate

analysis.

Factor relative risk p 95% CI

d aliv 7.703 0.006 2.379-153.363Sct cB 1.655 0.198 0.428-59.925

ag


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Fig 1 a. ovll svivl v wih wih SIadH. B. ev svivl v wih wih SIadH i pis

wih lig iss.

Pis wih SIadH h sigil high pbbili vll svivl (66.4% vss 50.8%) v svivl (68.6%

vss 43.3%) p wih SIadH.

Fig 2 a os SIadH i Bmt/PBSct cBt. B. WBc s SIadH i Bmt/PBSct cBt.

SIadH vlp li i pis wih cBt h i hs wih Bmt, h i bs WBc h s SIadH

w lw i pis wih cBt h i hs wih Bmt.

ii s si lvl w i

bw h. Hwv, sv sps sh s siz,

sl, igii libs w bsv i 8(50.0%) h 16 pis wih cBt, whs i

h 10 pis wih Bmt/PBSct. this i ws

sisill sigi (p=0.007). aiill, SIadH

vlp li i pis wih cBt (i s,

19.5 s Sct; g, 15 54 s) h i hs

wih Bmt (i s, 46 s Sct; g, 18

74 s), h i bs WBc h s SIadH w lw i pis wih cBt (i, 1.1 x

109 /l; g, 0.1 4.2 x 109 /l) h i hs wih Bmt

(i, 3.1 x 109/ l; g, 2.5 13.3 x 109 /l) (Fig 2).

ths is w sisill sigi (P < 0.01).

SIADH Complicated with SCT

pp 239-245


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Table 4

Bmt, PBSct(=10) cBt(=16)

G l 7 10

l 3 6ag (i, s l) 5.5 5mii vl si 121.5 120

(i, l/l)

os SIadH (i, ) 46 19.5

WBc s SIadH 3.1 1.1

(i, 109 /l)Sv sp SIadH 0 6

nlgil sql 1 4

dIScuSSIon

Hpi is s s i h ssi i lvl blw 136 l p

li. Hpi is ll isb

i liil pi. css hpi

il.9, 10 th s q ss hpi xl si lss viig ih,

hpi ihsis, g i hpi h

SIadH. Hpvli iss xl l

si lss piipl s hpi. I h

hpi is pgssiv, hh, s, viig,sl ps, lhg, slssss, isii,

pss fxs b bsv. cpliis

sv pil vlvig hpi il sizs,

, p bi g, spi s, bis hii, h. th sqs hpi sis i g hil

ppsl w.11

I s, spisigl, SIadH ws bsv

pis Sct, xpl. Hpi, l SIadH, hs b ssi wih vis iplsi

gs, ilig viisi, lphsphi,

isi hip.12, 13 o lsis vl gs

ii iig iiig gi w

ssi wih SIadH. SIadH hs b p bssi wih w hlgi isss sh s nHL

Hgkis iss.14-17 th s SIadH

i nHL is hgh b ih vi lkli-iig

hhp i ivsi i h pii gl.

chbi l. hv p h ss nHL issii wih HPS SIadH hv pps

iv hphsis.14 o pi wih B-ll nHL

iv hhp pi h s SIadH.

I his pi, s kis sh s IL-1 tnF-

sil h hphli shsis ls

bh adH ipi lsig h (crH).

crH is h si ipi isl,whih i sppss h si gs adH.

a Sct, kis sh s IL-2 IFn- h

t-ll xpsi, i xi t lls l

kill ll spss, pi iil lphgs p tnF- IL-1.18, 19 F hss, his SIadH Sct b spl

s i lsig ki.

aliv is isk s SIadH i

lsis. Sct HLa ish l ql pli sv GVHd

i is kw h lvls kis lik tnF-

IL-6 high.20 os hpi i pis

wih SIadH 15 74 s Sct. this i

gs h i wh GVHd vlps. thskis i SIadH. Pis

wih SIadH h high svivl h hs wihSIadH. mlivi lsis vl l SIadH s

ssi wih svivl i. alhgh h s

is l, kis hgh b l wih SIadH ipv svivl s i- .

o igs vl h pis wih cBt h

li s, lw WBc h s,

sv sps h hs wih Bmt/PBSct. thsspisig igs xl ip si

wh ivsigig h his SIadH llwig

Sct. rl, p-g i is

(PIr), hiz b high-g v wigh gi,

hv b pps s l php ps-cBti i21, 22 PIr vlps i 9 s

cBt, i is spl h his sls

ki i spli. Isigl, PIr

hs b p Bmt/PBSct. as pvisl

w, ilki-6 hs b p b ivlv iSIadH.23-25 ths, spl h SIadH i

s cBt ss shws ki i spi

lgh l pi, his i xpli i

p, h i s SIadH llwig cBt

Bmt/PBSct.

I lsi, SIadH is livl pliiwih Sct, spill i pis spl

liv . Fh, h i s

SIadH bsv llwig cBt Bmt/PBSct

sggs h h hiss spsibl SIadH i.

reFerenceS

1 ag HJ, mis ne: Hpi: rviw il. nw

Ryoji Kobayashi

pp 239-245


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vspssi qpi-2 i ipi w xi. cliileilg 58: 1-17, 2003

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h ssi wih s ll spli; liilis llwig s ll spli sig bl b w/piphl bl. B mw tspl ipss

8 B Fc, Shwz WB: th s ipppi si iii h. ai Jl mii 42: 790-806, 1967

9 P HB: th s ipppi iii hsi. th Iil Jl Bihis cllBilg 35 1495-1499, 2003

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11 ag HJ, mis ne: Hpi. nw egl Jl mii 342: 1581-1589, 2000

12 Ss JB, as mK, Hs HH: S

ipppi si iii h (SIadH) ilig iss. J I m. 238:97-110, 199513 Si S, cii S, S F, chisl P, Piiill n, Li L, L

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14 chbi a, mi I, H y, ohshi a, nishii t, mi

aB: S pppi si iii h i

pis wih lph-ssi hphgi s.a Hl 70: 53-55, 1995

15 ci m, chv L, ai J, rss J, Fvi r, HllmH, B a, S m: Piphl t-ll lphwih hphgi hisisis lliz h b wssi wih ipppi si iii h.Lki Lph 19: 511-514, 1995

16 eliki r, V e, Shih e: S ipppisi iii h i Hgkis iss. a J mSi 291: 126-127, 1986

17 Kl JG, Lg G: Ipppi iii hpliig hisii lph. ah I m 139: 307-308,1979

18 r P, F JL.: Ibilg g-vss-hsiss Bl rv 17:187-94, 2003

19 csskil ec, Kls Sm, cllis PW, clwll rd, all Pd,Si Le, mki HLJ, Gls aH, nwl ac: Filhpivi s b w spli:pssibl lv h vlp ps-splpliis lps. B mw tspli 15: 879-884, 1995

20 ngl a, Bish a, Bb c, Bk V: dsgli if kis i l b w spli.ckis cll ml th 4:161-167, 1998

21 Kishi y, Ki m, mikshi S, K y, mshig n, tshi t l. el i i -isi -blspli l pis. tspli 80: 34-40, 2005

22 nis H, tk S, ms K, ob t, uhi t, Ii H l. Sh- hx l l i is ipv s i bilil bl spli ls. B mw tspl 39: 31-39, 2007

23 msks G, Wb JS, mgik ma, G H, chss GP.Hphli-pii-l xis ivi sili ssi vspssi si b bi ilki-6 ihs: pil ipliis h s ipppivspssi si. J cli eil mb 79: 934-939, 1994

24 Giis d, Ilis I, mski m, mzs e, Pps I, Ksda l. Hphli-pii-l xis ilki-6

ivi i hil wih h s ipppisi iii h. J Pi eil mb 16:49-54, 2003

25 Ghbl mt, Sh G, Lx m, B t, dv dm,Bk KG l. mi lsis vls ilki-6 s vls p h hphl-hpphsl ss. JBil ch 278: 19280-19285, 2003

SIADH Complicated with SCT

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syndrome of inappropriate anti diuretic hormone secretion complicated with stem cell transplantation

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