TY - JOUR
T1 - Clonal chromosomal abnormalities appearing in Philadelphia chromosome–negative metaphases during CML treatment
AU - Issa, Ghayas C.
AU - Kantarjian, Hagop M.
AU - Gonzalez, Graciela Nogueras
AU - Borthakur, Gautam
AU - Tang, Guilin
AU - Wierda, William
AU - Sasaki, Koji
AU - Short, Nicholas J.
AU - Ravandi, Farhad
AU - Kadia, Tapan
AU - Patel, Keyur
AU - Luthra, Raja
AU - Ferrajoli, Alessandra
AU - Garcia-Manero, Guillermo
AU - Rios, Mary Beth
AU - Dellasala, Sara
AU - Jabbour, Elias
AU - Cortes, Jorge E.
N1 - Funding Information:
This study was funded by MD Anderson Cancer Center support grant (CA016672) and National Institutes of Health, National Cancer Institute (P01 CA049639).
Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/11/9
Y1 - 2017/11/9
N2 - Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph- occurred in 58 patients (10%); the most common were 2Y in 25 (43%) and trisomy 8 in 7 patients (12%). Response to TKI therapy was similar for patients with CCA/Ph- and those without additional chromosomal abnormalities (ACAs). We further categorized CCA/Ph- into those in which –Y was the only clonal abnormality, and all others. We found that patients with non –Y CCA/Ph- had worse failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS) compared with those without ACAs with the following 5-year rates: FFS (52% vs 70%, P 5 .02), EFS (68% vs 86%, P 5 .02), TFS (76% vs 94%, P < .01), and OS (79% vs 94%, P 5 .03). In a multivariate analysis, non –Y CCA/Ph- increased the risk of transformation or death when baseline characteristics were considered with a hazard ratio of 2.81 (95% confidence interval, 1.15-6.89; P 5 .02). However, this prognostic impact was not statistically significant when achieving BCR-ABL <10% at 3 months was included in the analysis. In conclusion, non –Y CCA/Ph- are associated with decreased survival when emerging in patients with chronic-phase CML across various TKIs. This trial was registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, and #NCT00050531 (imatinib); #NCT00254423 (dasatinib); #NCT00129740 (nilotinib); and NCT01570868 (ponatinib).
AB - Clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) metaphases emerge as patients with chronic phase chronic myeloid leukemia (CP-CML) are treated with tyrosine kinase inhibitors (TKIs). We assessed the characteristics and prognostic impact of 598 patients with CP-CML treated on clinical trials with various TKIs. CCA/Ph- occurred in 58 patients (10%); the most common were 2Y in 25 (43%) and trisomy 8 in 7 patients (12%). Response to TKI therapy was similar for patients with CCA/Ph- and those without additional chromosomal abnormalities (ACAs). We further categorized CCA/Ph- into those in which –Y was the only clonal abnormality, and all others. We found that patients with non –Y CCA/Ph- had worse failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS) compared with those without ACAs with the following 5-year rates: FFS (52% vs 70%, P 5 .02), EFS (68% vs 86%, P 5 .02), TFS (76% vs 94%, P < .01), and OS (79% vs 94%, P 5 .03). In a multivariate analysis, non –Y CCA/Ph- increased the risk of transformation or death when baseline characteristics were considered with a hazard ratio of 2.81 (95% confidence interval, 1.15-6.89; P 5 .02). However, this prognostic impact was not statistically significant when achieving BCR-ABL <10% at 3 months was included in the analysis. In conclusion, non –Y CCA/Ph- are associated with decreased survival when emerging in patients with chronic-phase CML across various TKIs. This trial was registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, and #NCT00050531 (imatinib); #NCT00254423 (dasatinib); #NCT00129740 (nilotinib); and NCT01570868 (ponatinib).
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U2 - 10.1182/blood-2017-07-792143
DO - 10.1182/blood-2017-07-792143
M3 - Article
C2 - 28835440
AN - SCOPUS:85033476197
SN - 0006-4971
VL - 130
SP - 2084
EP - 2091
JO - Blood
JF - Blood
IS - 19
ER -