An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: long-term results of the CMLALL1 trial.
Leuk Lymphoma
; 56(3): 630-8, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-24844361
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 BCR-ABL 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 BCR-ABL targeting without compromising clinical outcomes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Philadelphia Chromosome
/
Antineoplastic Combined Chemotherapy Protocols
/
Protein Kinase Inhibitors
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Imatinib Mesylate
Type of study:
Guideline
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Leuk Lymphoma
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2015
Document type:
Article
Affiliation country:
Australia