FROM THE JOURNAL OF CLINICAL ONCOLOGY
Philadelphia chromosome–like acute lymphoblastic leukemia, a high-risk subtype of childhood ALL, accounts for more than 24% of ALL in adults and is associated with poor outcome, according to gene-expression profiling in nearly 800 adults with B-cell ALL.
In the 798 subjects aged 21-86 years, Philadelphia chromosome–like (Ph-like) ALL accounted for 27.9% of ALL cases in those aged 21-39 years, 20.4% of cases in those aged 40-59 years, and 24% of cases in those aged 60-86 years. The overall 5-year event-free survival rate was inferior in those with Ph-like ALL vs. non–Ph-like ALL (22.5% vs. 49.3%), as was the 5-year overall survival (23.8% vs. 52.4%). Increasing age also was associated with inferior outcomes: 5-year event-free survival was 40.4%, 29.8%, and 18.9% in the age groups, respectively, and 5-year overall survival was 45.2%, 35.1%, and 28.4% in the groups, respectively, Kathryn G. Roberts, Ph.D., of St. Jude Children’s Research Hospital in Memphis and her colleagues reported online ahead of print (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.69.0073).
The investigators identified kinase-activating alterations in 88% of patients with Ph-like ALL. These included CRLF2 rearrangements in 51% of patients, ABL class fusions in 9.8%, JAK2 or EPOR rearrangements in 12.4%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%. Additionally, 11 new kinase rearrangements were identified, they said, noting that the diverse range of kinase-activating alterations – four of the newly identified rearrangements involved new kinase or cytokine receptor genes and seven involved new partner for previously identified genes – has important therapeutic implications.
Ph-like ALL in children is characterized by kinase-activating alterations amenable to treatment with tyrosine kinase inhibitors, but the prevalence in adults was unclear.
“These findings warrant the development of clinical trials in adults that assess the efficacy of TKIs, similar to those that are being established for pediatric ALL,” Dr. Roberts and her associates wrote.
This study was supported by grants and other awards, some to individual authors, from the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; Stand Up to Cancer, St. Baldrick’s Foundation, the American Society of Hematology, the Lady Tata Memorial Trust, the Leukemia Research Foundation, the National Cancer Institute, and the National Institutes of Health. Dr. Roberts reported that she is the inventor on a pending patent application related to gene-expression signatures for detection of underlying Philadelphia chromosome-live events and therapeutic targeting in leukemia.