High Frequency and Poor Outcome of Philadelphia Chromosome–Like ALL Reported in Adults


Key Points

  • Overall, adults with Ph-like ALL accounted for 24% of those with B-cell ALL aged 21 to 86 years.
  • Numerous kinase-activating alterations were identified in these patients.

In a study reported in the Journal of Clinical Oncology, Roberts et al found a high frequency of Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia (ALL) in adults with B-cell ALL and poorer outcome with conventional therapy in these patients.

Frequency of Disease

The frequency of Ph-like ALL was assessed by gene-expression profiling of 798 patients with B-cell ALL aged 21 to 86 years from several U.S., Canadian, and Italian clinical trial protocols.

Detailed genomic analysis was performed for 180 of 194 patients (24.3%) identified with Ph-like ALL. Patients with Ph-like ALL accounted for 27.9% of patients aged 21 to 39 years (young adults), 20.4% of those aged 40 to 59 years (adults), and 24.0% of those aged 60 to 86 years (older adults).

Poorer Outcomes

Overall, patients with Ph-like ALL had poorer 5-year event-free survival compared with patients with non–Ph-like ALL (22.5% vs 49.3%, P < .001), including 5-year rates of 24.1% vs 60.5% among young adults (P < .001) and 21.4% vs 38.7% among adults (P = .0021) and a 3-year rate of 8.0% vs 33.3% among older adults (P = .47).

Potential Therapeutic Targets

Kinase-activating alterations were found 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%). A total of 11 new kinase rearrangements were found, including 4 involving new kinase or cytokine receptor genes and 7 involving new partners for recognized genes.

The investigators concluded: “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.”

The study was supported by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital, a Stand Up to Cancer Innovative Research Grant and St Baldrick’s Foundation Scholar Award, an American Society of Hematology Scholar Award, a Lady Tata Memorial Trust Award, the Leukemia Research Foundation, National Cancer Institute grants, and National Institutes of Health grants.

Charles G. Mullighan, MD, of St. Jude Children’s Research Hospital, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.