High-dose cytarabine improves EFS for subset of infants with acute lymphoblastic leukemia
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High-dose cytarabine improved EFS among a subset of infants with acute lymphoblastic leukemia, according to study results published in Blood.
Minimal residual disease clearance appeared to predict favorable outcomes, researchers noted.
“Although 90% of children with ALL are cured nowadays, children aged younger than 1 year with ALL who harbor the KMT2A gene rearrangement [KMT2A-r] are still a challenging population to treat, with a reported EFS rate of 50%,” Daisuke Tomizawa, MD, PhD, head of the division of leukemia and lymphoma at the National Center for Child Health and Development’s Children Cancer Center, in Tokyo, told Healio. “The Japan Children’s Cancer Group has tried to improve outcomes for these patients by treating them with allogeneic hematopoietic stem cell transplant since the 1990s, but the observed improvement was modest. In addition, recent evidence suggests no clear benefit of HSCT for infants with ALL, and it could lead the survivors to suffer from severe late effects.”
The Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial evaluated the use of chemotherapy plus high-dose cytarabine in early intensification with and without allogeneic HSCT. Researchers also assessed the role of minimal residual disease.
The study included 90 infants with ALL categorized as low risk (n = 15), intermediate risk (n = 19) and high risk (n = 56) based on KMT2A status, age and presence of central nervous system leukemia. Only patients in the high-risk category had the option to undergo allogeneic HSCT.
The 3-year EFS rate for infants with KMT2A-r ALL served as the primary endpoint.
At median follow-up of 5.4 years (range, 1.5-7.8), results showed 3-year overall EFS of 94.4% in the intermediate-risk group and 56.6% in the high-risk group.
Researchers also reported 3-year EFS rates of 66.2% among infants with KMT2A-r ALL in the intermediate-risk and high-risk groups, and 93.3% among infants with germline KMT2A ALL in the low-risk group.
Results of multivariable analysis showed poor prognostic factors included female sex and minimal residual disease status greater than or equal to 0.01% at the end of early consolidation.
“The 3-year EFS for infants with KMT2A-r ALL is the best among all the studies conducted worldwide — the outcome was even better for infants with early clearance of minimal residual disease measured by flow cytometry,” Tomizawa said.
However, he added that caution is needed when interpreting the results because of the small sample size.
“Still, this study demonstrates better outcomes are achievable with the currently available chemotherapies along with aggressive supportive care, if one could clear MRD in an early phase of the therapy,” Tomizawa said. “Additionally, this treatment approach could safely restrict HSCT to carefully selected cases without compromising their outcome. The introduction of a novel therapeutic approach is still needed as a substantial number of infants with KMT2A-r ALL still suffer from recurrent/refractory leukemia, although no one knows what is right at the moment.”
Tomizawa and colleagues are currently examining the role of clofarabine in the ongoing MLL-17 trial, as well as the hypomethylating agent azacitidine for relapsed cases.
“There are other novel therapeutics of interest, such as blinatumomab [Blincyto, Amgen], chimeric antigen receptor T-cell therapies and the molecular targeted agents, BCL-2 inhibitors and menin inhibitors. We are continuing discussion for future collaboration with United States and European colleagues, considering the rarity of this disease.”
For more information:
Daisuke Tomizawa, MD, PhD, can be reached at National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan; email: tomizawa-d@ncchd.go.jp.
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