TY - JOUR
T1 - Clinical Algorithms for the Treatment of Patients With Chronic Myeloid Leukemia
T2 - The 2010 Perspective
AU - Jabbour, Elias
AU - Fullmer, Amber
AU - Cortés, Jorge E.
AU - Kantarjian, Hagop
N1 - Publisher Copyright:
© 2010 Elsevier Inc.
PY - 2010/6
Y1 - 2010/6
N2 - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation because of toxicity (intolerance). In patients for whom standard-dose imatinib therapy (400 mg/day) fails, imatinib dose escalation (600-800 mg/day) is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacologic profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse event tolerance level, and risk factors.
AB - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation because of toxicity (intolerance). In patients for whom standard-dose imatinib therapy (400 mg/day) fails, imatinib dose escalation (600-800 mg/day) is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacologic profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse event tolerance level, and risk factors.
KW - AP24534
KW - BCR-ABL
KW - Bosutinib
KW - Dasatinib
KW - Imatinib
KW - Nilotinib
KW - Omacetaxine
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U2 - 10.3816/CLML.2010.s.001
DO - 10.3816/CLML.2010.s.001
M3 - Article
C2 - 20529808
AN - SCOPUS:77957357810
SN - 2152-2650
VL - 10
SP - S6-S13
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -