Credit: St Jude Biomedical
Communications
Risk-directed therapy can level the playing field for patients with BCR-ABL1-like acute lymphoblastic leukemia (ALL), new research suggests.
Using minimal residual disease (MRD) and other risk factors to guide treatment intensity allowed patients withBCR-ABL1-like ALL to have survival rates comparable to those of other B-ALL patients.
The research also revealed that not all BCR-ABL1-like ALL patients have high-risk disease.
Ching-Hon Pui, MD, of St Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these results in the Journal of Clinical Oncology.
Patients with BCR-ABL1-like ALL tend to have poor outcomes, so Dr Pui and his colleagues evaluated the utility of risk-directed therapy in these and other B-ALL patients.
The team assessed patients enrolled in the Total Therapy XV study between 2000 and 2007. They were 1 to 18 years of age at diagnosis. There were 344 subjects with adequate samples for gene expression profiling.
Forty patients (11.6%) had BCR-ABL1-like ALL. They were significantly more likely than other study participants to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction.
The researchers monitored patients and adjusted their treatment intensity based on MRD at days 19 and 42. The treatment regimen was described in JAMA in 2009.
The MRD monitoring combined with conventional risk factors, such as patient age and white blood count at diagnosis, demonstrated that BCR-ABL1-like ALL is not a uniformly high-risk disease.
Forty percent of BCR-ABL1-like ALL patients were actually classified as having low-risk disease because they had other favorable clinical or biological features and no MRD at the end of remission induction.
The other 60% were classified as having standard-risk or high-risk disease. The group included 6 patients who underwent transplant.
There were no significant differences in event-free or overall survival in patients with BCR-ABL1-like ALL and the other ALL patients. At 5 years, event-free survival was 90.0% ± 4.7% and 88.4% ± 1.9%, respectively. And 5-year overall survival was 92.5% ± 4.2% and 95.1% ± 1.3%, respectively.
When available, more sophisticated genetic testing should be used to identify which of the B-ALL patients with high levels of MRD have the BCR-ABL1-like ALL subtype, Dr Pui said. Many of these patients have genetic alterations that make them responsive to tyrosine kinase inhibitors (TKIs) and possibly other targeted therapies.
For example, in this study, the researchers evaluated genetic abnormalities in 25 BCR-ABL1-like ALL patients. Eleven had a genomic rearrangement of CRLF2, 6 had fusion transcripts responsive to ABL TKIs or JAK inhibitors, and 7 had mutations involving the Ras signaling pathway.
“In the future, genetic testing will likely be used at diagnosis to identify [BCR-ABL1-like ALL] and direct patients to the best targeted therapy,” Dr Pui said, “possibly including some drugs that are currently experimental.”
