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 μM for 72h) and then mafosfamide (30-90 μg/ml for 30min) followed by 2 weeks in culture with cytokines (100ng/ml each of stem cell factor, granulocyte colony-stimulating factor and thrombopoietin). Treatment with 1.0μM imatinib, 60μg/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.
Original language | English (US) |
---|---|
Pages (from-to) | 575-582 |
Number of pages | 8 |
Journal | Bone marrow transplantation |
Volume | 37 |
Issue number | 6 |
DOIs | |
State | Published - Mar 2006 |
Keywords
- CD34
- Chronic myelogenous leukemia (CML)
- Imatinib
- Imatinib refractory
- Mafosfamide
- Purging
ASJC Scopus subject areas
- Hematology
- Transplantation