Successful autologous stem cell collection in patients with chronic myeloid leukemia in complete cytogenetic response, with quantitative measurement of BCR-ABL expression in blood, marrow, and apheresis products

Abstract

Imatinib mesylate is the initial therapy of choice for chronic myeloid leukemia in chronic phase (CML-CP), but in some patients, the disease becomes resistant to imatinib. Autologous stem cell transplantation using cells collected while in complete cytogenetic response (CCyR) may represent a therapeutic option for these patients. We mobilized and collected autologous CD34⁺ stem cells from 20 CML-CP patients in CCyR, 19 of whom were taking imatinib, and measured BCR-ABL expression in the apheresis products, blood and bone marrow using real-time quantitative PCR (RQ-PCR). Stem cells were mobilized with G-CSF 10 µg/kg daily for 5 days. In patients whose initial collection was <2×10⁶ CD34⁺ cells/kg, G-CSF dose was increased to 10 µg/kg twice daily on the second attempt, and imatinib was held for 14 days if a third attempt was necessary. All 20 patients successfully mobilized the target yield of 2 to 5×10⁶ CD34⁺ cells/kg; 16 reached target yield with the first mobilization. The median number of CD34⁺ cells collected was 4.4 (range, 2.0 – 8.4)×10⁶/kg in a median of 3 (range, 2 – 6) apheresis days. Of 17 patients whose stem cell products were evaluable by RQ-PCR, 11 (65%) had ≥1 daily product with undetectable BCR-ABL; 4 of these (24%) had no detectable BCR-ABL in any apheresis products. BCR-ABL expression in apheresis products was correlated with levels of expression in the blood and marrow prior to mobilization. No patient has yet required transplantation. With median follow-up of 18 months, all patients remain in CCyR and 9 of 16 (54%) have undetectable BCR-ABL in the most recent blood and marrow sample.

Keywords:

• Chronic myeloid leukemia
• imatinib mesylate
• autologous stem cell mobilization
• BCR-ABL
• minimal residual disease