Abstract
We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCRABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph+ ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCRABL targeting without compromising clinical outcomes.
Original language | English |
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Pages (from-to) | 630-638 |
Number of pages | 9 |
Journal | Leukemia and Lymphoma |
Volume | 56 |
Issue number | 3 |
DOIs | |
Publication status | Published or Issued - 1 Mar 2015 |
Keywords
- Chemotherapeutic approaches
- lymphoid leukemia
- pharmacotherapeutics
- signaling therapies
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research