Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy

Zimu Gong, L. Jeffrey Medeiros, Jorge E. Cortes, Zi Chen, Lan Zheng, Yan Li, Shi Bai, Pei Lin, Roberto N. Miranda, Jeffrey L. Jorgensen, Timothy J. McDonnell, Wei Wang, Hagop M. Kantarjian, Shimin Hu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2541-2552
Number of pages12
JournalBlood Advances
Volume1
Issue number26
DOIs
StatePublished - Dec 12 2017
Externally publishedYes

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Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Protein-Tyrosine Kinases
Therapeutics
Chromosome Aberrations
TYK2 Kinase

ASJC Scopus subject areas

  • Hematology

Cite this

Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy. / Gong, Zimu; Medeiros, L. Jeffrey; Cortes, Jorge E.; Chen, Zi; Zheng, Lan; Li, Yan; Bai, Shi; Lin, Pei; Miranda, Roberto N.; Jorgensen, Jeffrey L.; McDonnell, Timothy J.; Wang, Wei; Kantarjian, Hagop M.; Hu, Shimin.

In: Blood Advances, Vol. 1, No. 26, 12.12.2017, p. 2541-2552.

Research output: Contribution to journalArticle

Gong, Z, Medeiros, LJ, Cortes, JE, Chen, Z, Zheng, L, Li, Y, Bai, S, Lin, P, Miranda, RN, Jorgensen, JL, McDonnell, TJ, Wang, W, Kantarjian, HM & Hu, S 2017, 'Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy', Blood Advances, vol. 1, no. 26, pp. 2541-2552. https://doi.org/10.1182/bloodadvances.2017011858
Gong, Zimu ; Medeiros, L. Jeffrey ; Cortes, Jorge E. ; Chen, Zi ; Zheng, Lan ; Li, Yan ; Bai, Shi ; Lin, Pei ; Miranda, Roberto N. ; Jorgensen, Jeffrey L. ; McDonnell, Timothy J. ; Wang, Wei ; Kantarjian, Hagop M. ; Hu, Shimin. / Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy. In: Blood Advances. 2017 ; Vol. 1, No. 26. pp. 2541-2552.
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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

PY - 2017/12/12

Y1 - 2017/12/12

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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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