Children treated with low-dose chemotherapy as induction for acute myeloid leukaemia achieve comparable remission rates and survival outcomes to those receiving standard regimens, a randomised non-inferiority trial has shown.

Published in Blood [link here], the findings also demonstrated less toxicity associated with the low-dose regimen including fewer serious events and faster haematologic recovery, along with reduced induction treatment costs.

“These findings support the low-intensity chemotherapy regimen as an effective and less toxic alternative for remission induction in paediatric AML,” concluded the researchers from the Children’s Hospital of Soochow University in China.

They conducted a trial of 438 children with newly diagnosed AML from Chinese medical centres who were randomly assigned to low-dose cytarabine, mitoxantrone or idarubicin, and granulocyte colony-stimulating factor (G-CSF) or standard-dose induction chemotherapy (cytarabine, daunomycin, and etoposide).

All patients received two induction cycles with either low or standard dosing followed by consolidation with standard chemotherapy and/or hematopoietic stem cell transplantation post remission.

Findings for low-dose versus standard-dose induction regimens included:

• Complete remission (CR)/CR with incomplete count recovery rates after induction: 95.1% vs 95.3%, P = .922
• Measurable residual disease <0.1% after induction II: 87.4% vs 87.1%, P = .922
• 4-year overall survival: 81.3% vs 83.6%, P = .611
• 4-year event-free survival: 61.5% vs 63.1%, P = .832
• 4-year cumulative incidence of relapse and refractory disease: 30.7% vs 25.1%, P = .210

While there was a similar incidence of neutropenia and thrombocytopenia after induction, the low-dose regimen was associated with significantly shorter median time to neutrophil (19 vs 22 days in induction I and 12 vs 15 days in induction II) and platelet recovery (13 vs 17 days in induction I and 3 vs 8 days in induction II).

There was also significantly fewer grade ≥3 toxicities in the low-dose arm, including febrile neutropenia (25.6% vs 50.0%), lung or sinus infection (9.5% vs 19.2%) and sepsis (4.2% vs 11.6%) following induction II.

Four patients in the experimental arm died during remission induction and 11 died in the standard dose arm, either from severe infections or bleeding in vital organs.

Professor Rishi Kotecha.

In an accompanying commentary [link here], WA paediatric haematologist and oncologist Professor Rishi Kotecha praised the researchers for a study that could potentially influence initial paediatric AML care in regions with limited resources.

But he cautioned against the strategy’s wide-scale use for the moment, pointing out non-significant differences that might require further exploration first such as the higher cumulative incidence of relapse in patients receiving low-dose therapy and a greater proportion of patients who went on to receive haematopoietic stem cell transplant in the low-dose group.

“It begs the question as to whether a reduction in initial therapy may influence the required intensity of subsequent therapy or relapse characteristics,” said Professor Kotecha, a top leukaemia researcher from Perth Children’s Hospital, University of Western Australia, Curtin University and The Kids Research Institute Australia.

Professor Kotecha added that revolutionary developments in B-cell acute lymphoblastic leukaemia (B-ALL) had renewed interest in the investigation of targeted inhibitors and immunotherapies in relapsed/refractory paediatric AML.

“This activity has led to considerable optimism that, in time, an equivalent promising novel therapeutic candidate will emerge for the treatment of AML. In that sense, the application of the critical findings from this study may be more universal, in which adaptation of low-dose strategies could be utilised to integrate novel therapies and replicate the success that has been achieved for B-ALL in children with AML,” he said.