Management of acute lymphoblastic leukemia should be driven in large part by patient age, according to new clinical practice guidelines issued by the National Comprehensive Cancer Network.
Adolescents and young adults between the ages of 15 and 39 years benefit from the intensive therapies used to treat children, while older adults are thought to be less tolerant of the high-dose pediatric regimens, explained Dr. Patrick A. Brown.
"At this point, multiple studies have indicated that young adults with acute lymphoblastic leukemia [ALL] benefit significantly from pediatric-inspired treatments, and the new guidelines reflect this," said Dr. Brown, cochair of the NCCN panel that wrote the guidelines.
The treatment of older adults, on the other hand, is compromised relative to their younger counterparts, not only by their diminished tolerance of high-dose therapies but also by the presence in many adults of cytogenic abnormalities, including the translocation that results in the Philadelphia (Ph) chromosome, said Dr. Brown, director of the Pediatric Leukemia Program at the Kimmel Comprehensive Cancer Canter, Johns Hopkins University, Baltimore.
The Ph chromosome, a common feature in adult ALL patients but rare in children, leads to formation of the BCR-ABL fusion gene that is associated with a poor prognosis independent of age, he noted in an interview.
The new guidelines were presented March 17 at the conference in Hollywood, Fla.
They call for initial patient stratification based on Ph status and treatment of Ph-positive ALL patients with regimens that incorporate BCR-ABL-targeting tyrosine kinase inhibitors, such as imatinib (Gleevec). Imatinib is FDA approved for the treatment of adult patients with relapsed or refractory Ph-positive ALL.
Regarding treatment decisions, the guidelines recommend risk stratification by age, with adolescent and young adult patients aged 15-39 years being considered separately from the adult population 40 years and older. The guidelines also advocate that those 65 years and older be considered separately as well, but caution that "chronological age alone is a poor surrogate for determining patient fitness for therapy."
Consideration of allogeneic stem cell transplantation as a consolidation option following induction therapy in ALL patients should be based on Ph status and age, Dr. Brown said, noting that the guidelines recommend it for Ph-positive patients as well as PH-negative patients younger than 65 years who have high-risk features. These include elevated white blood cell count, hypodiploidy, or rearrangements of the mixed-lineage leukemia gene, not including those adult patients with preclusive comorbidities, such as organ dysfunction.