A novel triple purge strategy for eliminating chronic myelogenous leukemia (CML) cells from autografts.

Published

Journal Article

Imatinib-refractory chronic myelogenous leukemia (CML) patients can experience long-term disease-free survival with myeloablative therapy and allogeneic hematopoietic cell transplantation; however, associated complications carry a significant risk of mortality. Transplantation of autologous hematopoietic cells has a reduced risk of complications, but residual tumor cells in the autograft may contribute to relapse. Development of methods for purging tumor cells that do not compromise the engraftment potential of the normal hematopoietic cells in the autograft has been a long-standing goal. Since primitive CML cells differentiate more rapidly in vitro than their normal counterparts and are also preferentially killed by mafosfamide and imatinib, we examined the purging effectiveness on CD34(+) CML cells using a strategy that combines a brief exposure to imatinib (0.5-1.0 microM for 72 h) and then mafosfamide (30-90 microg/ml for 30 min) followed by 2 weeks in culture with cytokines (100 ng/ml each of stem cell factor, granulocyte colony-stimulating factor and thrombopoietin). Treatment with 1.0 microM imatinib, 60 microg/ml mafosfamide and 14 days of culture with cytokines eliminated BCR-ABL(+) cells from chronic phase CML patient aphereses, while preserving normal progenitors. This novel purging strategy may offer a new approach to improving the effectiveness of autologous transplantation in imatinib-refractory CML patients.

Full Text

Duke Authors

Cited Authors

  • Yang, H; Eaves, C; de Lima, M; Lee, MS; Champlin, RE; McMannis, JD; Robinson, SN; Niu, T; Decker, WK; Xing, D; Ng, J; Li, S; Yao, X; Eaves, AC; Jones, R; Andersson, BS; Shpall, EJ

Published Date

  • March 2006

Published In

Volume / Issue

  • 37 / 6

Start / End Page

  • 575 - 582

PubMed ID

  • 16435011

Pubmed Central ID

  • 16435011

International Standard Serial Number (ISSN)

  • 0268-3369

Digital Object Identifier (DOI)

  • 10.1038/sj.bmt.1705284

Language

  • eng

Conference Location

  • England