Differential in vitro cytotoxicity does not explain increased host toxicities from chemotherapy in Down syndrome acute lymphoblastic leukemia.

Leukemia Research
Mariela ValleKaren R Rabin

Abstract

Treatment-related toxicities such as mucositis and infections are both more frequent and more severe in children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) compared to non-DS ALL. Altered methotrexate pharmacodynamics play a role, but severe toxicities also occur in treatment courses that lack methotrexate. We hypothesized that this might be attributable to heightened cytotoxic effects of other ALL chemotherapeutic agents on DS versus non-DS host tissues. Panels of DS and non-DS lymphoblastoid cell lines (LCLs) and primary fibroblast cell lines were treated with asparaginase, dexamethasone, doxorubicin, mafosfamide and vincristine. LCL survival was assessed using the MTT assay, and fibroblast proliferation using the clonogenic survival assay. No significant differences were observed between DS and non-DS cell lines using either assay. Both DS and non-DS cell lines were resistant to dexamethasone at the maximal concentrations tested, and did not differ significantly in sensitivity to the other drugs studied. Thus, heightened in vitro cytotoxicity does not appear to account for the increased treatment-related toxicities observed in patients with DS ALL.

References

Sep 25, 2004·Pediatric Blood & Cancer·Jeffrey W Taub, Yubin Ge
Nov 18, 2005·Cancer Chemotherapy and Pharmacology·Terzah M HortonStacey L Berg
Oct 24, 2006·British Journal of Haematology·James A Whitlock
Mar 22, 2008·Genome Génome / Conseil National De Recherches Canada·Cesar A SommerFlavio Henrique-Silva

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Citations

Jan 30, 2009·The Oncologist·Karen R Rabin, James A Whitlock
Jul 3, 2010·Haematologica·Ana C Xavier, Jeffrey W Taub
Aug 25, 2017·Biochemical and Biophysical Research Communications·Dmitry D ZhdanovNikolai N Sokolov

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