title: In vitro drug resistance profiles of adult versus childhood acute lymphoblastic leukaemia.
abstract: The difference in the current cure rates between adult and childhood acute lymphoblastic leukaemia (ALL) may be caused by differences in drug resistance. Earlier studies showed that in vitro cellular drug resistance is a strong independent adverse risk factor in childhood ALL. Knowledge about cellular drug resistance in adult ALL is still limited. The present study compared the in vitro drug resistance profiles of 23 adult ALL patients with that of 395 childhood ALL patients. The lymphoblasts were tested by the MTT assay. The group of adult ALL samples was significantly more resistant to cytosine arabinoside, L-asparaginase, daunorubicin, dexamethasone and prednisolone. The resistance ratio (RR) was highest for prednisolone (31.7-fold) followed by dexamethasone (6.9-fold), L-asparaginase (6. 1-fold), cytosine arabinoside (2.9-fold), daunorubicin (2.5-fold) and vincristine (2.2-fold). Lymphoblasts from adult patients were not more resistant to mercaptopurine, thioguanine, 4-HOO-ifosfamide, mitoxantrone and teniposide. There were no significant differences in drug resistance between adult T-cell (T-) ALL (n = 11) and adult common/pre-B-cell (B-) ALL (n = 10). Additionally, adult T-ALL did not differ from childhood T-ALL (n = 69). There were significant differences between adult common/pre-B-ALL and childhood common/pre-B-ALL (n = 310) for prednisolone (RR = 302, P = 0.008), dexamethasone (RR = 20.9, P = 0.017) and daunorubicin (RR = 2.7, P = 0.009). Lymphoblasts from adults proved to be relatively resistant to drugs commonly used in therapy. This might contribute to the difference in outcome between children and adults with ALL.
authors.affiliation: Department of Paediatric Haematology and Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. hematonko@by.home.pl
authors.forename: J
authors.initials: J
authors.lastname: Styczynski
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: D R
authors.initials: DR
authors.lastname: Huismans
authors.forename: G J
authors.initials: GJ
authors.lastname: Schuurhuis
authors.forename: M
authors.initials: M
authors.lastname: Wysocki
authors.forename: A J
authors.initials: AJ
authors.lastname: Veerman
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001215:Asparaginase / Q000378:metabolism / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000378:metabolism / Q000627:therapeutic use; D003630:Daunorubicin / Q000378:metabolism / Q000627:therapeutic use; D003907:Dexamethasone / Q000378:metabolism / Q000627:therapeutic use; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000378:metabolism / Q000627:therapeutic use; D007069:Ifosfamide / Q000378:metabolism / Q000627:therapeutic use; D007223:Infant; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy / Q000378:metabolism; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism / Q000627:therapeutic use; D008875:Middle Aged; D008942:Mitoxantrone / Q000378:metabolism / Q000627:therapeutic use; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D011239:Prednisolone / Q000378:metabolism / Q000627:therapeutic use; D011379:Prognosis; D018709:Statistics, Nonparametric; D013713:Teniposide / Q000378:metabolism / Q000627:therapeutic use; D013866:Thioguanine / Q000378:metabolism / Q000627:therapeutic use; D014750:Vincristine / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D013713:Teniposide; D011239:Prednisolone; D008942:Mitoxantrone; D015122:Mercaptopurine; D001215:Asparaginase; D013866:Thioguanine; D007069:Ifosfamide; D015255:Idarubicin; D003630:Daunorubicin