Pediatric oncologist Bianca Goemans: ‘This study concerns children with recurrent AML that is difficult to treat. These are children with a refractory first AML relapse that does not respond well to the treatment or children whose AML has come back a second time. In the past, these children were usually treated palliatively. Nowadays, we opt for more intensive third-line treatment aimed at a cure more often. In this study, we focused on the chances of cure for children at this stage of their disease. We collected data from children eligible for third-line treatment. We also looked at factors that influence the likelihood of cure. We found that time to recurrence (shorter or longer after the previous diagnosis), type of third-line treatment, mutation in the FLT3 gene and the original treatment protocol influenced outcome.
The study was carried out in collaboration with the NOPHO-DBH-SHIP consortium. This is a collaboration of fourteen countries, including the Netherlands and thus the Máxima Center, that treat children with a first diagnosis of AML according to the same protocol. From 2004 to 2019, 277 of the 869 patients in the consortium had a leukemia recurrence. Of this group, 98 children had a first refractory relapse and 59 children had a second relapse. The researchers studied data from these 157 children together.
Real chance of cure
'We didn't really know from the literature what to expect, because most of the research in children takes place in the context of clinical trials and often at an earlier stage of treatment. This is because the children who participate in such studies have to be well enough to be eligible and so are not representative of the whole group,' says Bianca Goemans.
'From the clinic we know that the prognosis is not very favorable after third-line treatment. That was also confirmed in this study: after five years, only 14% of the children were still alive,' states Bianca. She immediately adds: 'We were positively surprised to see that a select group of patients can still be cured after third-line treatment. It is a real chance, which is there even at this late stage of treatment. This chance depends on several factors. If a child responds well enough to the new, third-line treatment and is fit enough for a (often second) stem cell transplant, the survival rate after five years is still about 40%. With this data, we can advise parents and children even better if they don't respond well to treatment after a first recurrence, or if the disease comes back a second time.'
Collaboration
New treatment protocols for children with recurrent AML are also being developed in another collaboration, PedAL/EuPAL, a consortium of several countries in the EU, UK, USA, Canada, Japan and Australia, supported by the Leukemia & Lymphoma Society (LLS). Bianca: 'For the first diagnosis of AML there is a standard treatment in the NOPHO-DBH-SHIP consortium, but for first and subsequent relapses there are no standard treatments. Now that we know how children fare at this stage of the disease, we can better assess whether the new treatments such as those in the PedAL/EuPAL consortium are truly better than the treatment we have been giving until now.'