Excellent outcomes for patients with B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses
Mené sur 228 enfants âgés entre 1 et 18 ans, atteints d'une leucémie lymphoblastique aiguë à précurseurs B avec récidive tardive au niveau de la moelle osseuse, cet essai randomisé analyse l'efficacité à long terme, du point de vue de la survie sans progression, et la toxicité d'un traitement d'induction à base d'idarubicine ou de mitoxantrone suivi, selon le niveau de maladie résiduelle, d'une greffe allogénique de cellules souches ou d'une chimiothérapie (durée médiane de suivi : 84 mois)
The prognosis for children with acute lymphoblastic leukaemia has improved substantially during the past 50 years. The improved survival results from the use of multi-agent, multiblock chemotherapy regimens that have been studied in randomised cooperative group clinical trials. Most gains have occurred in newly diagnosed patients, as the outcome for children with relapsed acute lymphoblastic leukaemia remains relatively poor.
In this issue of The Lancet Haematology, Catriona Parker and colleagues present long-term outcome data for patients with B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses who were enrolled in the ALLR3 clinical trial.1
ALLR3 was an international, open-label, randomised trial for patients aged 1–18 years with relapsed acute lymphoblastic leukaemia treated at 31 Children's Cancer and Leukaemia (CCLG) cooperative group centres. Patients were randomly assigned to receive an idarubicin-based or mitoxantrone-based remission induction regimen. The initial results of the ALLR3 trial were published in 2010, showing improved 3-year progression-free survival and overall survival in the mitoxantrone group. 3-year overall survival was 69%, leading other cooperative groups to adopt the ALLR3 backbone.
228 patients with late bone marrow relapses occurring more than 6 months after completion of front-line therapy were included in the long-term follow-up. Patients who had low minimal residual disease at end of induction (<10−4 cells, at timepoint 1) measured by real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements were non-randomly assigned to receive chemotherapy without haemopoietic stem-cell transplantation (HSCT). Those with extramedullary disease at relapse also received site-directed radiation. Patients with high minimal residual disease (≥10−4 cells) were non-randomly assigned to undergo HSCT. This study found a post-induction minimal residual disease at a cutoff of 1×10−4 cells to be highly prognostic for patients with late bone marrow relapses. With a median follow-up of 84 months, progression-free survival was 72% (95% CI 60–81) in patients with low minimal residual disease and 56% (46–65) in those with high minimal residual disease (p=0·0078). Notably, 30 (14%) of 211 patients were not able to follow the recommended treatment plan of stratification according to minimal residual disease level. Progression-free survival was higher in the mitoxantrone group, but unlike the overall cohort, 5-year overall survival did not differ significantly between the mitoxantrone and idarubicin groups among patients with late bone marrow relapses (75% [67–81] vs 63% [49–74]; p=0·10).
The Lancet Haematology , commentaire en libre accès, 2018