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Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma

Devereux, S; Corney, C; Macdonald, C; Watts, M; Sullivan, A; Goldstone, AH; Ward, M; ... Linch, DC; + view all (1998) Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma. GENE THER , 5 (3) 403 - 408.

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Abstract

We have performed a pilot study of MDR-1 gene transfer in patients receiving CD34-selected peripheral blood stem cell (PBSC) transplant for lymphoma. To ensure minimum engraftment thresholds and facilitate CD34 purification, mobilisation of >2 x 10(6) CD34 cells/kg was a condition for recruitment. Of 11 patients counselled for study entry, only five achieved this target in a single apheresis. In three consenting patients, purified CD34 cells were exposed to A12M1 MDR-1 retroviral supernatant for 6 h, cryopreserved then thawed and readministered following ablative chemotherapy. No delay in engraftment was observed, although one patient received additional back-up cells. Gene transfer was demonstrated by polymerase chain reaction (PCR) for vector-derived MDR-1 cDNA sequence in all cases. Analysis of peripheral blood and bone marrow cells after transplant has, however, shown no evidence of in vivo gene transfer with a follow-up of 12, 15 and 18 months. The effect of MDR-1 substrate drugs has not yet been tested as all patients remain in clinical and radiological remission of their lymphoma. These results confirm the difficulty of achieving in vivo gene transfer in human haemopoietic cells and indicate major logistical constraints in PBSC mobilisation in patients with relapsed and resistant disease in whom initial studies are appropriate.

Type: Article
Title: Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma
Keywords: gene transfer, lymphoma, multidrug resistance, retrovirus, BONE-MARROW TRANSPLANTATION, PROGENITOR CELLS, AMPHOTROPIC RETROVIRUS, HODGKINS-DISEASE, CORD-BLOOD, G-CSF, EXPRESSION, DNA, ENGRAFTMENT, CONTRIBUTE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/33578
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