Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial

Abstract

Medical Research Council and Leukaemia and Lymphoma Research.

An autologous leukemia cell vaccine prevents murine acute leukemia relapse after cytarabine treatment

“…Our experiments extend these findings by elucidating immunosuppressive activities in established leukemia and indicating that protection against acute leukemia can also be invoked during remission after cytarabine chemotherapy. Because this chemotherapeutic agent is in routine clinical use for leukemia induction and consolidation, 67,68 these results are of particular relevance clinically. 27,29 Our results support a previous in vivo study with C1498 in which mice treated with a granulocyte macrophage colony-stimulating factor-secreting irradiated cell vaccine 5 or 7 days after cytarabine treatment were protected against the development of leukemia, despite transient development of severe neutropenia and lymphopenia following chemotherapy.…”

Clinically defining and managing high-risk pediatric patients with acute lymphoblastic leukemia

“…Several recent large clinical trials have cemented this tool as the most important prognostic variable for the majority of children with both precursor B-ALL and T-cell ALL. 19,[54][55][56] In a study involving 2143 patients with NCI high-risk and standard-risk ALL, MRD measured by flow cytometry evaluated at the end of induction (day 29) was found to be the most significant prognostic factor, although NCI risk group maintained prognostic significance in multivariate analysis. 54 Therapeutic interventions were not made based on MRD in this series of trials.…”

“…Of the patients with evaluable MRD, 81% of all relapses occurred in those who were MRD high risk. 56 Within the context of the AIEOP BFM 2000 study, MRD measurement in patients with T-cell ALL was the most powerful prognostic factor for risk of relapse, 19 although prednisone poor response and early T-cell phenotype also maintained prognostic value. The kinetics of MRD clearance in patients with T-ALL is different with than in those with precursor B-ALL, with only a small proportion (16%) being MRD negative by day 33.…”

“…Improvements in outcomes for higher-risk patients in serial, nonrandomized trials have also been attributed to modifications of postinduction therapy, including the use of dexamethasone as the corticosteroid, the intensive use and formulation of asparaginase, 4,56 and intensification of consolidation/reinduction treatment. 32 Intensification of conventional chemotherapy has also been investigated within specific biological subsets of patients with ALL.…”

Cure trends in acute lymphoblastic leukemia: is it time for a revised concept of cure?

“…Another option is to reduce chemotherapy in patients predicted to have excellent outcome, for instance by low minimal residual disease levels at the end of induction. 11 In patients with Philadelphia-chromosome positive ALL, the addition of tyrosine kinase inhibitors (TKIs) may reduce the number of patients in need of stem cell transplantation, thereby reducing long-term side effects, although the long-term safety profile of TKIs when used in children still needs to be established. 12 Clearly, in order to describe outcome in terms of a revised concept of cure, cancer registries will need to capture data on longterm toxicity in patients in whom the malignancy has been successfully eradicated.…”