Exploring the Best Therapeutic Approach for Mixed Phenotype Acute Leukemia

New insights pertaining to the best therapeutic approach for mixed phenotype acute leukemia (MPAL), a rare and aggressive leukemia, have been uncovered at Children's Hospital Los Angeles (CHLA).

In a quantitative synthesis comprised of 20 years of scientific literature, clear benefits were found to coincide with commencing treatment of MPAL with a less-toxic regimen, such as achieving remission and potentially long-term survival. Findings from the study were published online in the journal Leukemia.

MPAL—which accounts for 2% to 5% of leukemia cases—has proven particularly challenging to treat over the years, and this fact is underscored by the 5-year survival rates of less than 50%. The disease affects both children and adults and contains characteristics of 2 more-common forms of leukemia: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

However, due to a lack of consensus on a best treatment approach, physicians face difficulty on deciding whether to treat patients with therapy for ALL, AML, or a hybrid of both approaches.

"Because this disease is so rare, we haven't had clinical trials with thousands of patients to define the optimal therapy," said Etan Orgel, MD, MS, a specialist in MPAL and a physician in the Center for Cancer and Blood Diseases at Children's Hospital Los Angeles in a recent statement. "Instead, we have many small, isolated, and often-conflicting case reports published in widely diffuse journals around the world. It's disjointed."

In an effort to more effectively decipher available research and provide more directive treatment guidance for physicians, Dr. Orgel and his team conducted the first-ever systematic review and meta-analysis of observational studies on MPAL. Searching more than 17,000 published studies and eventually narrowing that list to 252 relevant papers from 33 countries covering 1,499 patients, the team included studies using both the European Group and World Health Organization definitions of MPAL.

In their research, the team found that patients initially treated with ALL therapy, a significantly less-toxic regimen, were 3 to 5 times more likely to enter into a complete remission compared with AML-treated patients.

"This makes a really convincing case that starting with ALL therapy is beneficial on all fronts, from remission to overall survival—if not from increasing survival, then from decreasing side effects," commented Maria Maruffi, MD, the first author on the study.

While only found in studies reporting patient results as a group, patients starting with ALL chemotherapy were twice as likely to survive. However, in studies reporting individual patient results, survival appeared to be comparable in both groups, a finding that researchers were unable to explain. The researchers noted that worst outcomes had been observed in patients whi received hybrid therapy.

In regard to next steps, Dr Orgel added, "This research provides key insights to helping guide physicians treating patients walking in the door today. But it also highlights the critical need for a clinical trial to definitively determine the best therapy for MPAL and help move treatment for this rare disease forward."