TY - JOUR
T1 - Role of tyrosine kinase inhibitors in the management of philadelphia chromosome-positive acute lymphoblastic leukemia
AU - Mathisen, Michael S.
AU - O'Brien, Susan
AU - Thomas, Deborah
AU - Cortes, Jorge
AU - Kantarjian, Hagop
AU - Ravandi, Farhad
N1 - Funding Information:
none; D. Thomas: Consulting fees from Pfizer and payment for speaking from Novartis and Bristol-Myers-Squibb; J. Cortes: Consulting fees from Novartis, Bristol-Myers-Squibb, Ariad, Chemgenex, and Pfizer; H. Kantarjian: Grants or consulting fees from Novartis, Bristol-Myers-Squibb, and Pfizer; F. Ravandi: Research grants and consulting fees from Novartis and Bristol-Myers-Squibb.
PY - 2011/9
Y1 - 2011/9
N2 - The Philadelphia chromosome is the most common cytogenetic abnormality found in adult patients diagnosed with acute lymphoblastic leukemia. The result of this abnormality is the BCR-ABL protein, a constitutively active kinase involved in cell signaling and survival. When managed with multiagent chemotherapy regimens alone, patients have traditionally had an inferior outcome in terms of remission duration and overall survival when compared with patients who are Philadelphia chromosome- negative. Small-molecule tyrosine kinase inhibitors, such as imatinib and dasatinib, directly inhibit the BCR-ABL kinase, offering a targeted approach as a therapeutic option. As a result of several clinical trials with adequate follow-up, imatinib combined with chemotherapy represents the current standard of care for patients with newly diagnosed disease. Allogeneic stem cell transplantation has previously been the only modality to offer the potential for a cure, and it still should be considered for all patients deemed able to tolerate such an intervention. Second-generation tyrosine kinase inhibitors, such as dasatinib, may further improve the outcome in these patients. The role of molecular monitoring and the use of tyrosine kinase inhibitors after stem cell transplantation are areas of active investigation, and the results of ongoing trials will help to clarify the optimal management of these patients.
AB - The Philadelphia chromosome is the most common cytogenetic abnormality found in adult patients diagnosed with acute lymphoblastic leukemia. The result of this abnormality is the BCR-ABL protein, a constitutively active kinase involved in cell signaling and survival. When managed with multiagent chemotherapy regimens alone, patients have traditionally had an inferior outcome in terms of remission duration and overall survival when compared with patients who are Philadelphia chromosome- negative. Small-molecule tyrosine kinase inhibitors, such as imatinib and dasatinib, directly inhibit the BCR-ABL kinase, offering a targeted approach as a therapeutic option. As a result of several clinical trials with adequate follow-up, imatinib combined with chemotherapy represents the current standard of care for patients with newly diagnosed disease. Allogeneic stem cell transplantation has previously been the only modality to offer the potential for a cure, and it still should be considered for all patients deemed able to tolerate such an intervention. Second-generation tyrosine kinase inhibitors, such as dasatinib, may further improve the outcome in these patients. The role of molecular monitoring and the use of tyrosine kinase inhibitors after stem cell transplantation are areas of active investigation, and the results of ongoing trials will help to clarify the optimal management of these patients.
KW - ALL
KW - Acute lymphoblastic leukemia
KW - Chemotherapy
KW - Complications
KW - Dasatinib
KW - Imatinib
KW - Ph+ ALL
KW - Philadelphia chromosome
KW - Stem cell transplantation
KW - Therapy
KW - Treatment
KW - Tyrosine kinase inhibitors
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UR - http://www.scopus.com/inward/citedby.url?scp=80055063164&partnerID=8YFLogxK
U2 - 10.1007/s11899-011-0093-y
DO - 10.1007/s11899-011-0093-y
M3 - Article
C2 - 21660654
AN - SCOPUS:80055063164
SN - 1558-8211
VL - 6
SP - 187
EP - 194
JO - Current Hematologic Malignancy Reports
JF - Current Hematologic Malignancy Reports
IS - 3
ER -