DlcLE TIP DERGlsI (JOURNAL OF MEDICAL SCHOOL) C:27 S:3-4 2000

APLASTiK ANEMiDE GM-CSF VE G-CSF'NiN YUKSEK DOZ METiL

PREDNizOLON TEDAvisi iLE KAR~ILA~TIRILMASI

Yrd.Doc;.Dr. Naci TiFTiK 1 Doc;.Dr.Orhan AYYILDIZ2

Yrd.Doc;.Dr.Abdurrahman I~IKDOGAN3 Prof.Dr.Ekrem MUFTUOOLU.4

QZET

Bu r;a//fjma ap/astik anemi/i hasta/arda k%ni stimiile edici faktor/er (CSF) veyOksek doz metil predniz%n tedavisini (H/VMP) karfj//afjt/rmak amac/ i/e yap/Id/. CSFveri/en hastalarm yafj orta/ama/afl,21.6:t8,42 4'0 erkek 6's/ kadm idi. H/VMP verilenhasta/afln ise yafj orta/ama/an 27,41:t:14,06 o/up, 3'0 erkek 7'si kadgn idi. CSF hasta/ara4-6 Ngr/kg/gOn dozda 6-15 gOn sOre i/e uygu/and/. Her iki grub un tedavi oncesi (O.gOn),3, 7 ve 14.g0n notrofil deger/erine bak//d/. CSF a/an grupta orta/ama notrofi/ deger/eriO.gOnde 430:t:392/mm3, 7.g0nde 680:t:603/mm3, 14.g0nde 750:t:506/mm3 iken HIVMPa/an grupta 490:t:264/mm3, 7.g0nde 670:t:440/mm3, 14.g0nde 1060:t:604/mm3 saptand/.Her iki grupta da tedavi oncesine gore 14.g0nde an/am/I notrofil deger/erine u/afj//dl(P<O,01). Her iki grupta gOn/er arasmda istatistikse/ olarak an/am bu/unmamasma kaf!jm(P>O,05), 14.g0nde H/VMP tedavisinde daha bafjan// sonur;/ar almd/. Aplastikanemilerdeki aglf notropeni (500/mm3'On a/tl) oram CSF a/an grupta tedavi oncesi %60iken 14. gOnde %40, HIVMPa/an grupta ise tedavi oncesi %60 iken 14.g0nde %20bulundu.

Anahtar Kelime/er; Ap/astik anemi, CSF (koloni stimOle edici faktor), HIVMP(YOksek doz meti/ predniz%n tedavisi).

GiRi~

Aplastik anemi kemik iliginde hipoplazi veya aplazi, periferik kandapansitopeni ile karakterize bir anemidir. Aplastik aneminin tedavisinde supportiftedavinin yanlnda immuno Supresif tedavi yapllmakta ve ilgili merkezlerdekemik iligi transplantasyonu (KiT) tatbik edilmektedir. immunosupresif tedaviolarak ALG (anti lenfosit globulin), siklosporin-A veya HIVMP kullamlmaktadlr(1,2,3). Aplastik anemi patogenezinde faktorlerden birisinin de stem hOcrelerininyok veya yetersiz olmasl, hematologlan hemapoetik bOyOmefaktorlerini buhastallkta tek ba~lna veya kombine olarak kullanmaya yoneltmi~tir. Yapylanc;all~malarda erken progenitor hOcrelere etkili interlokin-1, interlokin-3,interlokin-6 veya SCF (steel faktor) ve daha sonraki donemlere etkili GM-CSF(granOlosit makrofaj-CSF), G-CSF (granOlosit-CSF) ve eritropoetin kullamlmaa~amaslndadlr (4). Bu c;all~madaki amalt, CSF'lerin aplastik anemili hastalarOzerindeki etkisini ara~tlrmak ve HIVMP tedavisi verilen aplastik anemilihastalarla kar~lla~tlrmaktlr.

(1,2,3,4) Dicle Oniversitesi Tlh FakQltesiIQHastallklan ABD Hematoloji BD DlvARBAKIR

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MATERYAlveMETOD

Diele Oniversitesi Tip FakOltesi k: Hastallklan ABD Hematoloji BilimDalmda 1992-1994 Ylllan arasmda aplastik anemili 20 hasta 9all§maya dahiledildi. Bu hastalardan 10'una CSF (GM-CSF ve G-CSF) verilirken 10'una daHIVMP (Tablo-1) uygulandl. CSF verilen hastalann 4'0 erkek, 6'sl kadm olup,ya§ ortalamalan 21.6:t8.42 idi. HIVMP verilen hastalann ise 3'0 erkek Tsi kadlnolup, ya§ ortalamalan 27.41:t14.06 idi. Her iki grup notropenik olup, takipedildikleri sOre i9inde destek tedavisi dl:;;mda (antibiyotik, kan OrOnleri vs.)herhangi ba§ka bir ila9 almadl. CSF hastalara iv infOzyon ile 50ee %5 dextrozi9inde 30 dk'da veya se verildi. Tedavi 6-15 gOnsOre ile 4-6 Ngr/gOn dozlardauygulandl. Gruplann 0.,3.,7. ve 14. gOnlerdeki notrofil saYlsma ETDA'II kanallnarak Abbotteell DYN 1600 eihazmda empedans teknigi ile baklldl. Eldeedilen degerlerin istatistiksel analizi student-t testi (gruplann anlamllllk testi)kullamlarak yaplldl.

Tablo 1: HIVMP (YOksekdoz metil prednizolon tedavi protokolu).

30mg/kg/gOn 3 gOn .20mglkg/gOn 4 gOn

1Omg/kg/gOn 7 gOn

5mg/kg/gOn 15 gOn

2,5mg/kg/gOn ...idame

BUlGUlAR

Her iki grubun tedavi oneesi notrofil degerlerinde fark yoktur. Her ikigrupta 3.ve7. gOnlerde tedavi oneesine gore notrofil degerlerinde fark yok iken(p>0.05), 14. gOnde fark vardl (p<0.01 ).Her iki grup kar§lla:;;trrrldlgmda ise3.,7., ve 14. gOnlerin kendileri arasmda fark yoktu (p>0.05). Aneak 14. gOndeistatistiksel olarak anlamh olmasada HIVMP tedavinin daha iyi sonu91arverdiQigozlendi (Tablo-2). CSF alan aplastik anemili hastalarda aglr notropenili hastaoram tedavi oneesi %60 iken, 14.g0n sonrasmda %40, HIVMP alan hastalardatedavi oneesi %60 iken, 14.g0n sonrasl %20 idi (Tablo:3).

Tablo 2: Her iki grubun istatistiksel analizi notrofil saYlsl/mm3.

O.gOn 3.g0n 7.g0n 14.g0n

CSF n:10 430392 460378 680603 750506

HIVMP n:10 490264 580270 670440 1040481

P degeri >0,05 >0,05 >0,05 >0,05

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Tablo3: Notrofil SaYlsymn 500/mm3'On altmdaolduguhastasaYlslve %oranlan.

TARTI$MA

Aplastik anemili hastalarda CSF kullanlml ile ilgili ~ok saYlda <;ali~mavardlr (5,6,7,8). HIVMP tedavisi ise ATG (anti-timosit globulin) ve KiT'in <;okpahall olmasl nedeni ile alternatif bir tedavi olarak dO~OnOlmO~kandegerlerinde belirgin yOkselmeler saptanml~tlr (9,10,11). Bizim <;ah~mamlzdaher iki grupta 14.g0nde anlamll notrofil degerlerine ula~lldl (p<0.01). Bu daliteratOr verileri ile desteklendi (5,6,9,10). Her iki grup ortalama notrofil degerlerikar~lla~tlnldlglnda ise aralannda anlamll bir fark bulunamadl (p>O.05). Bunakar~m her iki gruba aglr notropeni (SOO/mm3'Onaltl) a<;lsmdan baklldlglndaise, tedavi oncesi bu oran her iki grupta %60 iken. tedavi sonraslnda CSF olangrupta %40, HIVMP olan grupta ise %20 idi. Bu sonu<;larlaher iki grup araslndaanlamll fark olmasa da; 14.g0nde HIVMP tedavisi azda olsa daha ba~anll idi.Ancak CSF yOksek dozda verilmemi~ti. LiteratOrde yOksek doz CSFkullanlldlglnda sonu<;larmdaha ba~arlli oldugu bildirilmi~tir (7,8). Buna kar~1nAshihara ve arkada~lan (12) ATG ve HIVMP tedavisine diren<;liya~11bir aplastik

anemili hastaya uzun sOreli 75-150 f.lgr/gOndedozlarda CSF verilmi~, 6 aysonra her 3 kan seri elemanlarmm normale d6ndOgO gorOlmO~tOr. CSFimmunsupressif ila<;larla kullanllml~ ve hastalann remisyon oranlan artml~tlr(13). Sonuc;olarak, aplastik anemideCSF dO~Okdozlarda kullanllml~ olup.HIVMP tedavisi kadar ba~arrll idi. Bu nedenle CSF, aplastik anemidenotropeninin derinligini ve sOresiniazaltmak i<;inalternatif bir teadavi olarak g6zonOndebulundurulmalidlr.

O.gun 3.gun 7.gun 14.gun

CSF n:10 6(%60) 6(%60) 5(%50) 4(%40)

HIVMPn:10 6(%60) 5(%50) 5(%50) 2(%20)

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SUMMARY

COMPARISON OF GM-CSF AND G-CSF WITH HIGH DOSE

METHYLPREDNYSOLONE THERAPY ON APLASTYK ANEMYA

In this study, it has been aimed to compare colony stimulating factor(CSF) and high dose methylprednisolone therapy (HIVMP) on the patients withaplastik anemia. The group given CSF were consist of 10 patients (6 female, 4male). The mean age of this group was 21,6j:8,42/mm3. The group givenHIVMP were consist of 10 patients ,too (7 female,3 male). And the mean age ofthis group was 27,4h14,06. CSF was given 4-6 I-lgr/kg/dayfor 6-15 days in theboth groups the neutropils were counted before the treatment (0 day) and afterthe therapy at the 3rd.,7th. and 14th. days. In the group given CSF the meancount of neutrophils were 430392/mm3 before the treatment, 680603/mm3 atthe 7th. day and 750j:506/mm3 at the 14th. day. In the other group (givenHIVMP) it was 490~64 before the treatment, 670j:440 at the 7th. day and1060j:604 at the 14th day. In comparison with the pretreatment period there

"was a significant increase in neutropil counts in both of the groups at the 14th.day (p<O.01). Although there is no significant difference between the days inthe both group (p<O.05), it was observed that the HIVMP therapy was moresuccesful in the 14th. day. The severe neutropenic ratio (under 500/mm3) of thepatients with aplastic anemia was 60% before CSF. And it becomes 40% at the14th. day of CSF. As severe neutropenia ratio was 60% before treatment itdecreased to 20% at the 14th. day in the group given HIVMP.

Key Words: Aplastic anemia, CSF(colony-stimulating factor), HIVMP(high dose methylprednisolone.

KAYNAKLAR

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7. Weide R,Lyttellon M,Samsan D,et al.:Sustained trilineage responce in apatient with ALG-resistans severe aplastik anemia after treatment withG-CSF,erythropoetin and cyclosporin A:Association of recovery with markedelevation of serum alkaline phosphatase. Br.J.Haematol 85: 608-610, 1993.

8. Kojima S, Matsuyuma T.: Stimulation of granulopoesis by highdoserecombinant human granulocyte colony-stimulating factor in children withaplastik anemia and very severe neutropenia.Blood 83: 1474-1478,1994.

9 .Issaragrisil S,Tangnai-Trisorona Y,Sriseriwan T. et al.:Methyl prednisolonetherapy in aplastik anemia :Corrolation of in vitro tests and Iymphocytesubsets with clinical response. Eur.J.HaematoI40: 343-349, 1988.

10. Yokoh K,Kimura S, Wada K,et al .:Aplastik anemia associated with minimalserum M-protein treated succesfully with repeated bolus methyl prednisolontherapy. Rinsho-Ketsueki 31: 506-510, 1990.

11. Ita R,Kawauchi K, Toki T,et al.:Severe aplastik anemia successfully treatedwith cyclosporin-A and prednisolon. Rinsto-Kketsueks 30: 2157-2162,1989.

12. Ashihara E,Shimazaki C,Hirata T, et al.:Trilinage response in severeaplastik anemia following long-term therapy with recombinant humangranulocyt colony-stimulating factor. Acta Haematol 90: 159-161, 1993.

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