TY - JOUR
T1 - Poor outcomes associated with +der(22)t(9;22) and −9/9p in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor
AU - Short, Nicholas J.
AU - Kantarjian, Hagop M.
AU - Sasaki, Koji
AU - Ravandi, Farhad
AU - Ko, Heidi
AU - Cameron Yin, C.
AU - Garcia-Manero, Guillermo
AU - Cortes, Jorge E.
AU - Garris, Rebecca
AU - O'Brien, Susan M.
AU - Patel, Keyur
AU - Khouri, Maria
AU - Thomas, Deborah
AU - Jain, Nitin
AU - Kadia, Tapan M.
AU - Daver, Naval G.
AU - Benton, Christopher B.
AU - Issa, Ghayas C.
AU - Konopleva, Marina
AU - Jabbour, Elias
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n = 36), dasatinib (n = 74), or ponatinib (n = 42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P = 0.42) or overall survival (OS; P = 0.51). When individual ACAs were evaluated, +der(22)t(9;22) and/or −9/9p in the absence of high hyperdiploidy (HeH) was present in 16% of patients and constituted a poor-risk ACA group. Patients with one or more poor-risk ACAs in the absence of HeH had significantly shorter RFS (5-year RFS rate 33% versus 59%, P = 0.01) and OS (5-year OS rate 24% versus 63%, P = 0.003). Poor-risk ACAs were prognostic in patients who received imatinib and dasatinib but not in those who received ponatinib. By multivariate analysis, this poor-risk ACA group was independently associated with worse RFS (HR 2.03 [95% CI 1.08-3.30], P = 0.03) and OS (HR 2.02 [95% CI 1.10-3.71], P = 0.02). Patients with Ph+ ALL who have +der(22)t(9;22) and/or −9/9p in the absence of HeH have relatively poor outcomes when treated with chemotherapy plus a TKI.
AB - In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n = 36), dasatinib (n = 74), or ponatinib (n = 42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P = 0.42) or overall survival (OS; P = 0.51). When individual ACAs were evaluated, +der(22)t(9;22) and/or −9/9p in the absence of high hyperdiploidy (HeH) was present in 16% of patients and constituted a poor-risk ACA group. Patients with one or more poor-risk ACAs in the absence of HeH had significantly shorter RFS (5-year RFS rate 33% versus 59%, P = 0.01) and OS (5-year OS rate 24% versus 63%, P = 0.003). Poor-risk ACAs were prognostic in patients who received imatinib and dasatinib but not in those who received ponatinib. By multivariate analysis, this poor-risk ACA group was independently associated with worse RFS (HR 2.03 [95% CI 1.08-3.30], P = 0.03) and OS (HR 2.02 [95% CI 1.10-3.71], P = 0.02). Patients with Ph+ ALL who have +der(22)t(9;22) and/or −9/9p in the absence of HeH have relatively poor outcomes when treated with chemotherapy plus a TKI.
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U2 - 10.1002/ajh.24625
DO - 10.1002/ajh.24625
M3 - Article
C2 - 28006851
AN - SCOPUS:85011932309
SN - 0361-8609
VL - 92
SP - 238
EP - 243
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 3
ER -