Improved outcome for children with acute lymphoblastic leukemia or non-Hodgkin lymphoma: results of the EORTC 58951 trial

The EORTC 58951 trial for children with average risk acute lymphoblastic leukemia or non-Hodgkin lymphoma evaluated dexamethasone versus prednisolone in induction and vincristine and corticosteroid pulses during continuation therapy.[1] Continuation therapy involving reinductions of vincristine with corticosteroids has been shown to improve the outcome in non-intensive protocols such as the Berlin-Frankfurt-Muenster (BFM). In the EORTC Children’s Leukemia Group study, 411 patients were randomly assigned to receive prednisolone, 202 patients, or dexamethasone, 201 patients (eight patients were non-randomly assigned to prednisolone). For the pulses, the corticosteroid used was that assigned at induction.

At a median follow-up of 6.3 years, the 6-year disease-free survival rate was 90.6% for pulses (standard error [SE], 2.1%) and 82.8% for non-pulses (SE, 2.8%, hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in both corticosteroid randomized groups (HR = 0.56 for the prednisolone group and HR = 0.59 for the dexamethasone group). The authors conclude that for average-risk patients treated according to BFM-like protocols, pulses should be reintroduced as a standard component of therapy.

It is interesting to note that the analysis at a 4.8 year follow-up of the I-BFM-SG ALL intergroup trial indicated that vincristine and dexamethasone corticosteroids pulses would fail to provide benefit.[2] Despite having had the total number of patients was limited in this study, the final analysis of the EORTC Children’s Leukemia Group trial at a median follow-up of 6.3 years was able to show the benefit of pulses in improving the outcome. The importance of this result was stressed in a Nature Reviews: Clinical Oncology Research Highlight.[3]

John Bean
EORTC, Medical Science Writer

[1] Barbara De Moerloose, Stefan Suciu, Yves Bertrand, et al. for the Children’s Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer (EORTC). Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951. Blood 116: 36-44, 2010.

[2] Conter V, Valsecchi MG, Silvestri D, et al. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet 369(9556):123-131, 2007.

[3] Rebecca Kirk. Pediatric oncology: Pulsed treatment in continuation therapy improves disease-free survival in children with hematologic malignancies Pulsed treatment in continuation therapy. Nature Rev Clin Onc 7:552, 2010.