ALL in infants aged younger than 12 months is both rare and biologically different from ALL in older children. Although the cure rate in children with ALL has improved from around 10% 40 years ago to 80% currently, this improved cure rate has not been seen in infants under 12-months, where event-free survival (EFS) has been reported in the range 17-45%.
Dr Rob Pieters, Erasmus MC-Sophia Childrens Hospital, Rotterdam, The Netherlands and colleagues did a study of 482 infants from 22 countries aged under one-year – The Interfant-99 trial. The patients were arranged in risk-order following their peripheral blood response to a 7-day prednisone pre-treatment (prednisone is a standard ALL treatment). They were then given a hybrid treatment regimen based on the standard treatment protocol for ALL, incorporating some elements designed for treatment of acute myeloid leukaemia (AML).
With an average follow-up time of just over three years, the researchers found that 58% of patients who received the hybrid treatment were in complete remission, while at four years follow-up 47% had experienced EFS. In previous studies of ALL, EFS has been reported in the range 17-45%. The hybrid treatment protocol did not produce more toxic effects than in previous regimens. The authors say: “Patients treated with our hybrid protocol, and especially those who responded poorly to prednisone, had higher EFS than most reported outcomes for treatment of infant ALL.”
The authors believe that the use of cytarabine in low-dose and high-dose sequential course could have led to the improved outcomes in Interfant-99. In-vitro studies have shown that infant lymphoblasts are highly sensitive to cytarabine.
The authors conclude: “We believe that this hybrid treatment protocol will be used as the standard for continuing international collaborative studies that aim to further improve outcomes for acute lymphoblastic leukaemia in infants.”
In an accompanying Comment, Dr Josep-Maria Ribera and Dr Albert Oriol, Institut Català d’Oncologia-Hospital Universitari Germans Trias I Pujol, Badalona, Spain, say “Despite the good results of the Interfant-99 protocol, there is a long way to go....new strategies, mainly derived from knowledge of the disease at a genomic level, are urgently needed. They will lead to the development of novel agents that will hopefully be integrated within the current cytarabine-based strategies. To achieve this goal, international collaboration must continue in this rare leukaemia.”
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