TY - JOUR
T1 - Managing Philadelphia chromosome-positive acute lymphoblastic leukemia
T2 - Role of tyrosine kinase inhibitors
AU - Ravandi, Farhad
N1 - Funding Information:
The author takes full responsibility for the content of this publication and confirms that it reflects his viewpoint and medical expertise. He also wishes to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support. Bristol-Myers Squibb did not influence the content of the manuscript, nor did the author receive financial compensation for authoring the manuscript.
PY - 2011/4
Y1 - 2011/4
N2 - Before the introduction of tyrosine kinase inhibitors, the prognosis for patients with Philadelphia chromosomepositive acute lymphoblastic leukemia was poor. The treatment of choice, stem cell transplantation, is a potentially curative option, but it is available only for a minority of patients and is associated with significant risk of morbidity and mortality. Although imatinib is largely effective, a substantial proportion of patients become resistant or intolerant to it. The activity of imatinib may be enhanced by coadministration with chemotherapy; such treatment is effective in many patients. Dasatinib is established as a second-line treatment in patients with resistance to or intolerance of imatinib. Recent data suggest that dasatinib, either alone or in combination with chemotherapy, has utility as first-line therapy. Dasatinib is more potent than imatinib, is less susceptible to drug-resistance mechanisms, and has been shown to penetrate the blood-brain barrier, making it potentially effective for treating central nervous system disease. Patients who relapse during treatment with dasatinib frequently carry the T315I mutation of BCR-ABL. Future regimens combining dasatinib with an agent able to inhibit this mutation may further improve outcome.
AB - Before the introduction of tyrosine kinase inhibitors, the prognosis for patients with Philadelphia chromosomepositive acute lymphoblastic leukemia was poor. The treatment of choice, stem cell transplantation, is a potentially curative option, but it is available only for a minority of patients and is associated with significant risk of morbidity and mortality. Although imatinib is largely effective, a substantial proportion of patients become resistant or intolerant to it. The activity of imatinib may be enhanced by coadministration with chemotherapy; such treatment is effective in many patients. Dasatinib is established as a second-line treatment in patients with resistance to or intolerance of imatinib. Recent data suggest that dasatinib, either alone or in combination with chemotherapy, has utility as first-line therapy. Dasatinib is more potent than imatinib, is less susceptible to drug-resistance mechanisms, and has been shown to penetrate the blood-brain barrier, making it potentially effective for treating central nervous system disease. Patients who relapse during treatment with dasatinib frequently carry the T315I mutation of BCR-ABL. Future regimens combining dasatinib with an agent able to inhibit this mutation may further improve outcome.
KW - Philadelphia chromosome-positive
KW - acute lymphoblastic leukemia
KW - acute lymphocytic leukemia
KW - allogeneic stem cell transplantation
KW - dasatinib
KW - imatinib
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U2 - 10.1016/j.clml.2011.03.002
DO - 10.1016/j.clml.2011.03.002
M3 - Review article
C2 - 21575924
AN - SCOPUS:80052820891
SN - 2152-2650
VL - 11
SP - 198
EP - 203
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 2
ER -