1. ¹Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. ²Terry Fox Laboratories, BC Cancer Research Center, Vancouver, BC, Canada
3. ³Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr H Yang, Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA. E-mail: hyang@mdanderson.org

Received 17 October 2005; Revised 2 December 2005; Accepted 5 December 2005; Published online 23 January 2006.

Abstract

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 M for 72 h) and then mafosfamide (30–90 g/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 M imatinib, 60 g/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.