In vitro cellular drug resistance adds prognostic information to other known risk-factors in childhood acute lymphoblastic leukemia.
Leukemic cells from 230 children with newly diagnosed B-cell precursor ALL were tested for in vitro drug resistance to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. During follow-up, 24 relapses occurred in the 159 children with MRD <0.1% day 29. The risk of any relapse was correlated to vincristine and doxorubicin resistance, with a relative risk of 3.7 (95% CI 1.3-10.5; p=0.016) for patients resistant to both drugs. There was a significant correlation also for the subgroup with extra-medullary relapses. Our findings indicate that analysis of drug resistance can add prognostic information to other known risk-factors including MRD.
Lönnerholm
Gudmar
G
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. gudmar.lonnerholm@kbh.uu.se
Thörn
Ingrid
I
Sundström
Christer
C
Frost
Britt-Marie
BM
Flaegstad
Trond
T
Heyman
Mats
M
Jonsson
Olafur Gisli
OG
Harila-Saari
Arja
A
Madsen
Hans O
HO
Porwit
Anna
A
Schmiegelow
Kjeld
K
Söderhäll
Stefan
S
Wesenberg
Finn
F
Vettenranta
Kim
K
Larsson
Rolf
R
Forestier
Erik
E
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011239:Prednisolone / Q000494:pharmacology; D011379:Prognosis; D012307:Risk Factors; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin; D011239:Prednisolone