Fludarabine, treosulfan and etoposide sensitivity and the outcome of hematopoietic stem cell transplantation in childhood acute myeloid leukemia.
BACKGROUND
The prognostic role of the ex vivo drug resistance profile has not yet been proved in childhood acute myeloid leukemia (AML). The aim of the study was the analysis of the impact of the ex vivo drug resistance profile in a cohort of 44 children with AML undergoing hematopoietic stem cell transplantation (HSCT).


METHODS
Myeloblasts for drug resistance testing were obtained from the bone marrow either on diagnosis or at relapse, before the HSCT procedure and were tested by the MTT assay.


RESULTS
Children who relapsed after transplantation showed higher ex vivo resistance of the leukemic blasts to etoposide, mercaptopurine, thioguanine, fludarabine, mitoxantrone and treosulfan than those who stayed in remission. Despite being nondiscriminative, the combined ex vivo drug resistance profile to fludarabine, treosulfan and etoposide (FTE score) was the strongest prognostic factor by multivariate analysis.


CONCLUSIONS
The combined drug resistance profile to fludarabine, treosulfan and etoposide may be useful for better stratification of children with AML undergoing stem cell transplantation or to indicate the necessity for additional post-transplant therapy.
Styczynski
Jan
J
Department of Pediatric Hematology and Oncology, Medical College, Nicolaus Copernicus University, ul. Curie-Sklodowskiej 9, 85-094 Bydgoszcz, Poland. jstyczynski@cm.umk.pl
Toporski
Jacek
J
Wysocki
Mariusz
M
Debski
Robert
R
Chybicka
Alicja
A
Boruczkowski
Dariusz
D
Wachowiak
Jacek
J
Wojcik
Beata
B
Kowalczyk
Jerzy
J
Gil
Lidia
L
Balwierz
Walentyna
W
Matysiak
Michal
M
Krawczuk-Rybak
Maryna
M
Balcerska
Anna
A
Sonta-Jakimczyk
Danuta
D
D000208:Acute Disease; D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002066:Busulfan / Q000031:analogs & derivatives / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D042381:Granulocyte Precursor Cells / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000601:surgery*; D008297:Male; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
D000970:Antineoplastic Agents; D005047:Etoposide; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine