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

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• 作者：Nicholas J. Short ; Hagop M. Kantarjian ; Koji Sasaki ; Farhad Ravandi ; Heidi Ko ; C. Cameron Yin ; Guillermo Garcia-Manero ; Jorge E. Cortes ; Rebecca Garris ; Susan M. O'Brien ; Keyur Patel ; Maria Khouri ; Deborah Thomas ; Nitin Jain ; Tapan M. Kadia ; Naval G. Daver ; Christopher B. Benton ; Ghayas C. Issa ; Marina Konopleva and Elias Jabbour
• 刊名：American Journal of Hematology
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：92
• 期：3
• 页码：238-243
• 全文大小：608K
• ISSN：1096-8652

文摘

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.