ALLTogether - a European treatment protocol for children and young adults with acute lymphoblastic leukaemia (ALL)

The aims of the ALLTogether study are to improve survival and quality of survival for children and young adults with ALL. ALL in young people has excellent outcome with >90% survival in children and about 75% in young adults. However, patients still die of diseases after relapse as a result of under-treatment.

Furthermore, a considerable fraction of younger patients are over-treated: All patients risk treatment-related death and some suffer long-term side-effects or secondary cancer. The rates of death from disease and death from therapy are almost the same for children. To show improvement with such good survival, large populations are needed.

Study groups from the five Nordic countries, Estonia and Lithuania (NOPHO), the UK (UKALL), the Netherlands (DCOG), Germany (COALL), Belgium (BSPHO), Ireland (SHOP) and France (SFCE) have designed a common treatment protocol as new standard of care for children and young adults with ALL. The risk-stratification is based on a novel, personalised algorithm using clinical characteristics, genetic changes in the leukaemia and response to therapy.

Planned interventions:

Over-treatment will be addressed by two randomizations in lower-risk patients to treatment-reduction (omission of anthracyclin and/or omission of pulses of Vincristine+Dexamethasone) in patients <16 years old.

One randomization will test a new drug (Inotuzumab) and one will test addition of 6-Thioguanine to maintenance to reduce relapse-risk in higher risk patients.

Tyrosine kinase inhibitors will be given to patients with ABL-class fusions.

High-risk B-lineage patients may be stratified to CAR-T therapy as an alternative to high-risk blocks and stem-cell transplant to reduce the side-effects.

In addition, the prognostic impact of more sensitive diagnostic tests (flow-cytometry) for CNS-leukaemia will be tested prospectively to increase the diagnostic accuracy and open the possibility of therapy-adaption in the future.

The protocol will, based on a personalised risk-approach, define a platform for diagnosis and treatment onto which randomized as well as non-randomised interventions and translational studies can be added.

The planned randomisations may identify therapy that is less toxic, but equally efficacious for sub-groups of patients and innovative therapy may reduce relapses and death from ALL. Translational and other therapy-related research will be promoted.


Maria Nilsson

Maria Nilsson