TY - JOUR
T1 - Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy
AU - Gong, Zimu
AU - Medeiros, L. Jeffrey
AU - Cortes, Jorge E.
AU - Chen, Zi
AU - Zheng, Lan
AU - Li, Yan
AU - Bai, Shi
AU - Lin, Pei
AU - Miranda, Roberto N.
AU - Jorgensen, Jeffrey L.
AU - McDonnell, Timothy J.
AU - Wang, Wei
AU - Kantarjian, Hagop M.
AU - Hu, Shimin
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/12/12
Y1 - 2017/12/12
N2 - The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3). Based on BP risk associated with each ACA, patients were stratified into intermediate-1, intermediate-2, and HR groups, with a median duration of interval 2 of unreached, 19.2 months, and 1.9 months, respectively. There was no difference in durations of intervals 1 or 3 among 3 groups. Including patients without ACAs who formed the standard-risk group, the overall 5-year cumulative probability of BP was 9.8%, 28.0%, 41.7%, and 67.4% for these 4 groups, respectively. The pre-BP disease course in those who developed BP was similar regardless of cytogenetic alterations, and 84.4% of BP patients developed BP within the first 5 years of diagnosis. In summary, interval 2 is the predominant determinant of BP risk and patient outcome. By prolonging the duration of interval 2, TKI therapy mitigates BP risk associated with low-risk ACAs or no ACAs but does not alter the natural course ofCMLwithHR ACAs. Thus, we have identified a group of patients who have HR of BP and may benefit from timely alternative treatment to prevent onset of BP.
AB - The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3). Based on BP risk associated with each ACA, patients were stratified into intermediate-1, intermediate-2, and HR groups, with a median duration of interval 2 of unreached, 19.2 months, and 1.9 months, respectively. There was no difference in durations of intervals 1 or 3 among 3 groups. Including patients without ACAs who formed the standard-risk group, the overall 5-year cumulative probability of BP was 9.8%, 28.0%, 41.7%, and 67.4% for these 4 groups, respectively. The pre-BP disease course in those who developed BP was similar regardless of cytogenetic alterations, and 84.4% of BP patients developed BP within the first 5 years of diagnosis. In summary, interval 2 is the predominant determinant of BP risk and patient outcome. By prolonging the duration of interval 2, TKI therapy mitigates BP risk associated with low-risk ACAs or no ACAs but does not alter the natural course ofCMLwithHR ACAs. Thus, we have identified a group of patients who have HR of BP and may benefit from timely alternative treatment to prevent onset of BP.
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U2 - 10.1182/bloodadvances.2017011858
DO - 10.1182/bloodadvances.2017011858
M3 - Article
C2 - 29296906
AN - SCOPUS:85042411654
SN - 2473-9529
VL - 1
SP - 2541
EP - 2552
JO - Blood Advances
JF - Blood Advances
IS - 26
ER -