Prognostic impact of combined fludarabine, treosulfan and mitoxantrone resistance profile in childhood acute myeloid leukemia.
BACKGROUND
The role of cellular drug resistance in childhood acute myeloid leukemia (AML) has not yet been established. The aim of the study was the analysis of the clinical value of ex vivo drug resistance in pediatric AML.


METHODS
A cohort of 90 children with de novo AML were assayed for drug resistance profile by the 3-4,5-dimethylthiazol-2-yl-2,5-difenyl tetrazolium bromide (MTT) assay and prognostic model of in vitro drug sensitivity was analyzed.


RESULTS
Children who relapsed during follow-up showed higher in vitro resistance of leukemic blasts to most of the drugs tested, except for cytarabine, cladribine, vincristine, mercaptopurine and thioguanine. A combined in vitro drug resistance profile to fludarabine, treosulfan and mitoxantrone (FTM score) was defined and it had an independent prognostic significance for disease free survival in pediatric AML.


CONCLUSIONS
The combined fludarabine, treosulfan and mitoxantrone resistance profile to possibly may be used for better stratification of children with AML or indicate the necessity for additional therapy.
Styczynski
Jan
J
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Bydgoszcz, Poland. jstyczynski@cm.umk.pl
Wysocki
Mariusz
M
Dluzniewska
Agnieszka
A
Juraszewska
Edyta
E
Balwierz
Walentyna
W
Czyzewski
Krzysztof
K
Wieczorek
Maria
M
Olejnik
Igor
I
Krawczuk-Rybak
Maryna
M
Kuzmicz
Marta
M
Kowalczyk
Jerzy
J
Stefaniak
Jolanta
J
Badowska
Wanda
W
Sonta-Jakimczyk
Danuta
D
Szczepanski
Tomasz
T
Matysiak
Michal
M
Stanczak
Elzbieta
E
Malinowska
Iwona
I
Wachowiak
Jacek
J
Konatkowska
Benigna
B
Gil
Lidia
L
Balcerska
Anna
A
Kapuscinska
Lucyna
L
Szczepanek
Joanna
J
Kolodziej
Beata
B
Rafinska
Beata
B
Kubicka
Malgorzata
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D008942:Mitoxantrone; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine