Steroid scheduling change cuts early deaths in children with leukaemia, Indian trial finds

A simple change in the way steroids are given during treatment for childhood leukaemia could significantly reduce early treatment-related deaths without affecting cure rates, according to findings from a large Indian clinical trial involving more than 3,000 children.

The study, led by the Indian Childhood Collaborative Leukaemia (ICiCle) group and published in The Lancet Regional Health – Southeast Asia, found that administering steroids in short bursts rather than continuously during the initial phase of treatment halved early mortality among children with acute B-cell precursor acute lymphoblastic leukaemia (ALL).

The findings are particularly significant for India and other low- and middle-income countries, where treatment-related deaths remain a major challenge despite improvements in childhood cancer care. Severe infections linked to continuous steroid use are among the leading causes of early deaths during leukaemia treatment.

Lower mortality without compromising treatment success

Researchers compared the standard four-week continuous steroid regimen with a pulsed schedule in which steroids were given during weeks one, two and four of treatment.

Children receiving the pulsed regimen experienced substantially fewer early deaths. Treatment-related mortality fell from 3.5% in the continuous steroid group to 1.3% in the pulsed group.

Importantly, the modified approach did not reduce treatment effectiveness. Remission rates were approximately 98% in both groups, and survival outcomes remained similar, suggesting that the safer strategy did not compromise the likelihood of cure.

Acute B-cell precursor acute lymphoblastic leukaemia is a rapidly growing blood cancer that originates from immature B-cells in the bone marrow. It is the most common form of acute lymphoblastic leukaemia in children.

First multicentre randomised paediatric oncology trial in India

The findings come from the ICiCle-ALL-14 trial, described by researchers as the first multicentre randomised paediatric oncology trial conducted in India.

The trial enrolled more than 3,000 children with acute B-cell precursor acute lymphoblastic leukaemia across six major treatment centres in the country. The study was conducted by the ICiCle group, which includes researchers from the University of Manchester.

Childhood leukaemia survival rates now exceed 90% in many high-income countries. However, children in low- and middle-income countries continue to face a greater risk of dying during treatment, often because of infections that occur early in therapy.

Since 2013, the ICiCle group has been working to establish a consistent and modern treatment approach for children with leukaemia across India.

Anthracycline use linked to higher treatment-related mortality

The trial also identified another potential safety concern during induction treatment.

Researchers found that the early use of anthracyclines, a class of chemotherapy drugs widely regarded as highly effective against cancer, increased the risk of treatment-related deaths.

The study did not report that this approach improved survival sufficiently to offset the higher mortality risk, highlighting the need for careful evaluation of treatment intensity during the early stages of care.

Experts call findings a practical practice change

Professor Vaskar Saha of The University of Manchester and Tata Medical Center, the study’s lead author and founder of the ICiCle group, said the results demonstrated that a straightforward adjustment in treatment delivery could save lives.

“We show for the first time that a simple change in how we give steroids can save lives. By reducing continuous exposure, we appear to lessen the risk of severe infections without compromising the effectiveness of treatment. This is a practical, low-cost intervention that could be adopted widely, particularly in settings where treatment-related mortality remains high,” he said.

Professor Venkatraman Radhakrishnan of the Cancer Institute (WIA) said the study provided strong evidence that steroid scheduling itself influences induction mortality.

“The study provides robust randomised evidence that steroid scheduling itself is a modifiable determinant of induction mortality. The lack of any detriment in MRD response or survival makes this a particularly compelling practice change,” he said.

Why the findings matter

Steroids are a cornerstone of induction therapy, the first phase of treatment aimed at achieving remission in acute lymphoblastic leukaemia. The ICiCle-ALL-14 trial suggests that changing the timing of steroid exposure, rather than increasing or decreasing treatment intensity, may improve safety outcomes.

For countries where infection-related treatment deaths remain a persistent barrier to improving childhood cancer survival, the findings point to a low-cost intervention that can be implemented without reducing remission or survival outcomes.

The study’s central message is clear: a modification in steroid scheduling reduced early treatment-related mortality from 3.5% to 1.3% while maintaining remission rates of around 98%, offering a potentially safer treatment pathway for children with acute lymphoblastic leukaemia.