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J Clin Oncol. 2017 Feb;35(4):394-401. doi: 10.1200/JCO.2016.69.0073. Epub 2016 Nov 21.

High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults.

Author information

1
Kathryn G. Roberts, Zhaohui Gu, Debbie Payne-Turner, Kelly McCastlain, Deqing Pei, Ilaria Iacobucci, Marcus Valentine, Stanley B. Pounds, Lei Shi, Yongjin Li, Jinghui Zhang, Cheng Cheng, and Charles G. Mullighan, St Jude Children's Research Hospital, Memphis, TN; Richard C. Harvey, I-Ming Chen, and Cheryl L. Willman, University of New Mexico Cancer Center, Albuquerque, NM; Alessandro Rambaldi, Manuela Tosi, and Orietta Spinelli, Ospedale Papa Giovanni XXIII, Bergamo, Italy; Jerald P. Radich, Fred Hutchinson Cancer Research Center, Seattle, WA; Mark D. Minden, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Jacob M. Rowe, Shaare Zedek Medical Center, Jerusalem, Israel; Selina Luger, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Mark R. Litzow, Mayo Clinic, Rochester, MN; Martin S. Tallman, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York; Peter H. Wiernik, Cancer Research Foundation of New York; Elisabeth Paietta, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Ravi Bhatia, The University of Alabama at Birmingham, Birmingham, AL; Ibrahim Aldoss and Guido Marcucci, City of Hope, Duarte, CA; Jessica Kohlschmidt, Krzysztof Mrózek, and Clara D. Bloomfield, Comprehensive Cancer Center, The Ohio State University, Columbus, OH; Wendy Stock, University of Chicago Medical Center, Chicago, IL; and Stephen Kornblau, Hagop M. Kantarjian, and Marina Konopleva, The University of Texas MD Anderson Cancer Center, Houston, TX.

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.

PMID:
27870571
PMCID:
PMC5455698
DOI:
10.1200/JCO.2016.69.0073
[Indexed for MEDLINE]
Free PMC Article

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