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Medical and Biological Sciences XXVI/2 - Collegium Medicum ...

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<strong>Medical</strong> <strong>and</strong> <strong>Biological</strong> <strong>Sciences</strong>, 2012, 26/2, 47-52<br />

ORIGINAL ARTICLE / PRACA ORYGINALNA<br />

Beata Kuryło-Rafińska, Beata Kołodziej, Małgorzata Kubicka, Mariusz Wysocki, Jan Styczyński<br />

DIFFERENTIAL EX VIVO DRUG RESISTANCE PROFILE IN FIRST<br />

AND SUBSEQUENT RELAPSED CHILDHOOD ACUTE MYELOID LEUKEMIA<br />

IN COMPARISON TO INITIAL DIAGNOSIS<br />

ZRÓŻNICOWANY PROFIL OPORNOŚCI EX VIVO NA CYTOSTATYKI W PIERWSZEJ<br />

I KOLEJNYCH WZNOWACH OSTREJ BIAŁACZKI MIELOBLASTYCZNEJ U DZIECI<br />

W PORÓWNANIU Z PIERWSZYM ROZPOZNANIEM<br />

Pracownia Onkologii Klinicznej i Eksperymentalnej, Katedra Pediatrii, Hematologii i Onkologii, <strong>Collegium</strong><br />

<strong>Medicum</strong> im. L. Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika<br />

Kierownik: prof. dr hab. n. med. Mariusz Wysocki<br />

Szpital Uniwersytecki nr 1 im. Jurasza w Bydgoszczy<br />

Dyrektor: Jarosław Kozera<br />

Summary<br />

B a c k g r o u n d . Current cure rate reach 50-60% of<br />

long-term survival in childhood acute myeloblastic leukemia<br />

(AML). In spite of continuous progress in therapy of AML,<br />

relapses still occur frequently in both children <strong>and</strong><br />

adolescents. The aim of this study was the analysis of the ex<br />

vivo drug resistance profile first <strong>and</strong> subsequent relapse in<br />

childhood AML in comparison to newly diagnosed AML.<br />

M e t h o d s . The results of 76 pediatric AML samples<br />

tested for drug resistance by the MTT assay were analyzed.<br />

Up to 22 drugs were tested for each patient.<br />

R e s u l t s . No significant differences between ex vivo<br />

drug resistance at first <strong>and</strong> subsequent relapse of childhood<br />

AML were found, <strong>and</strong> no drug was found for which<br />

significantly higher resistance of myeloblasts was observed<br />

at subsequent relapse, when compared to first relapse of<br />

AML. For most tested drugs, relapsed patients had higher ex<br />

vivo drug resistance profile than de novo AML patients. The<br />

median RR (relative resistance between relapsed <strong>and</strong> de novo<br />

diagnosed patients) value of all 22 drugs tested was 1.6. For<br />

five drugs, RR was significantly higher at relapse: idarubicin<br />

(1.8-fold), etoposide (5.9-fold), cytarabine (1.7-fold),<br />

fludarabine (3.7-fold) <strong>and</strong> busulfan (4.3-fold). For other four<br />

drugs, a trend for higher resistance at relapse was observed:<br />

for daunorubicin, mitoxantrone, L-asparaginase <strong>and</strong><br />

cladribine.<br />

Conclusion. Ex vivo drug resistance profile in<br />

relapsed childhood AML is higher in comparison to initial<br />

diagnosis, however we did not find differences in ex vivo<br />

drug resistance between first <strong>and</strong> subsequent relapse of<br />

AML.<br />

Streszczenie<br />

Wstę p . Aktualne wyniki leczenia w ostrej białaczce<br />

mieloblastycznej (AML) u dzieci sięgają 50-60%. Pomimo<br />

ciągłego postępu, nadal często występują wznowy choroby,<br />

zarówno u dzieci i u młodzieży. Celem pracy była ocena<br />

profilu oporności ex vivo na cytostatyki w trakcie pierwszej<br />

i kolejnej wznowy w stosunku do pierwszego rozpoznania<br />

w AML u dzieci.<br />

M e t o d y k a . Analizie poddano wyniki badań oporności<br />

na cytostatyki wykonanych przy użyciu testu MTT<br />

u 76 dzieci z AML. Badania przeprowadzono z użyciem 22<br />

leków.

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