EHA 2016
Improved survival in adult ALL
Dr Nina Toft - Rigshospitalet, Copenhagen, Denmark
I’m here to present de novo data. It’s a protocol used in treating ALL patients 1-45 years and it’s a known fact that children with ALL have a better survival than adults. After the year 2000 many publications came showing that young adults transferred to a paediatric ward had a better survival compared to young adults who were treated in an adult ward. So this led to the implementation of paediatric protocols in many countries and the Nordic and Baltic countries also approached this.
Our purpose of this research was to find out why children have a better survival than adults and my main focus today will be to show you if we could improve this survival by changing the protocol to these more intensified paediatric protocols.
The next slide is a bit busy but I want to show you the protocol which is quite complex and first some facts. We used one common protocol for all patients, 1-45 years. It’s Philadelphia negative ALL which is important to say. All patients had identical diagnostics and were risk stratified the same way and were treated the same way. They were divided into four risk groups and we have included 1509 patients, this was until the end of 2014, but the protocol continues. We are seven countries that united, that’s the Nordic countries, Denmark, Sweden, Norway, Iceland, Finland and then Lithuania and Estonia. We have now in this cohort 221 adult patients, when I say adult I mean 18 and up to 45, and we have now a median follow up of four years.
The protocol is shown here and the patient enters at day one. This is where they are divided into induction therapy which will last for four weeks. Depending on a few cytogenetic changes and P or G immune phenotype, they will have induction for four weeks and then we take a bone marrow and we evaluate the response to chemotherapy. We call it minimal residual disease and it’s done day 29, you see it here. If you have a good response you can continue in either a standard risk or an intermediate risk treatment. If you have a poor response you can go to high risk black therapy and if you have a very poor response day 29 you are directed to high risk, at least three blocks and then transplanted. Then you continue in your chosen arm. Then day 79 a new bone marrow is done and if you still have signs of leukaemia that is more than 0.1% by minimal residual disease methods, PCR and Flow, you are also directed to transplantation in first remission. Otherwise you continue and the total length is 2.5 years for all patients with maintenance therapy.
The results are shown here. These are the results for the whole cohort and, as expected, you see the young children here, they are 1-9 years old, they are known to have the best survival and it’s expected they do very well. This is event free survival. Here you have the teens and the teenagers, they are 10-17 years old, also very good survival. Here in yellow you have the adults that are 18-45. I’ve put in this line to show you the data that I have access to, this is the Danish cohort of patients, 108 patients treated before we initiated the paediatric treatment. So these patients are also Philadelphia negative, fully treated 2.5 years with a traditional adult regime. They have an event free survival of 42%. So we are pleased with the results and we expect to continue this.
In conclusion, we have improved the survival for adult patients 18-45 years. We showed that the cure rates are close to those of children. I don’t have time today to show you the different risk groups, there are four risk groups as I mentioned, but if you compare an adult in the standard risk group with a child in the standard risk group there is no difference. They do the same, the same goes for the high risk group; age is not an issue here. For the intermediate risk group there is a difference, adults do not do the same as children but it’s close.
So what we need now is further cooperation because we need to unite to get more patients so we can show new developments faster. We also need to find new risk criteria because, as for the intermediate risk group, something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not. And then we need new drugs because with this method we’ve reached the limit of toxicity that we find reasonable.
