New approaches to the management of Philadelphia-chromosome-positive acute lymphocytic leukemia.
The discovery of targeted ABL tyrosine kinase inhibitors has allowed significant advances in the treatment of de novo Philadelphia chromosome (Ph)-positive ALL. Whereas the outcome with standard chemotherapy was previously dismal, the use of imatinib in front-line therapy has improved relapse-free survival and overall survival, even in the absence of allogeneic stem cell transplantation in first complete remission (particularly for those with comorbidities or lack of a suitable donor). However, the emergence of resistance to imatinib presents a new therapeutic challenge. Novel tyrosine kinase inhibitors with enhanced inhibitory potency against ABL and other kinases may further improve on the results observed with imatinib. Optimal use of these novel agents in the treatment schema of Ph-positive ALL will be paramount in ensuring continued success in the eradication of this disease.
Thomas
Deborah A
DA
Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. debthomas@mdanderson.org
O'Brien
Susan
S
Cortes
Jorge
J
Kantarjian
Hagop
H
D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000601:surgery; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl