High frequency and poor outcome of Philadelphia chromosome-like acute lymphoblastic leukemia in adults
Date
2017
Authors
Roberts, K.G.
Gu, Z.
Payne-Turner, D.
McCastlain, K.
Harvey, R.C.
Chen, I.-M.
Pei, D.
Iacobucci, I.
Valentine, M.
Pounds, S.B.
Editors
Advisors
Journal Title
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Type:
Journal article
Citation
Journal of Clinical Oncology, 2017; 35(4):394-401
Statement of Responsibility
Kathryn G. Roberts, Zhaohui Gu, Debbie Payne-Turner, Kelly McCastlain, Richard C. Harvey, I-Ming Chen, Deqing Pei, Ilaria Iacobucci, Marcus Valentine, Stanley B. Pounds, Lei Shi, Yongjin Li, Jinghui Zhang, Cheng Cheng, Alessandro Rambaldi, Manuela Tosi, Orietta Spinelli, Jerald P. Radich, Mark D. Minden, Jacob M. Rowe, Selina Luger, Mark R. Litzow, Martin S. Tallman, Peter H. Wiernik, Ravi Bhatia, Ibrahim Aldoss, Jessica Kohlschmidt, Krzysztof Mrózek, Guido Marcucci, Clara D. Bloomfield, Wendy Stock, Stephen Kornblau, Hagop M. Kantarjian, Marina Konopleva, Elisabeth Paietta, Cheryl L. Willman, and Charles G. Mullighan
Conference Name
Abstract
Purpose: Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods: The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results: Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion: Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.
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© 2016 by American Society of Clinical Oncology