In a recently
published study, Nikolas Herold and Martin Jädersten from Karolinska University
Hospital show how acute myeloid leukaemia can be treated more effectively. They
have reused an already proven medicinal product.
Acute myeloid leukaemia (AML) is an aggressive
blood cancer with a high mortality that affects about 350 people annually in
Sweden. Over 70 percent of patients die within five years of falling ill. One
reason for the high mortality rate is that chemotherapy often has an inadequate
effect, which causes the disease to reoccur after some time.
The protein (SAMHD1) in the leukaemia cell has been shown to be a resistance
factor for the medicinal product cytarabine.
Nikolas Herold, a paediatrician at the Paediatric Oncology Clinic at Astrid Lindgren's Children's Hospital in Solna, discovered with his research group at Karolinska Institutet that another medicinal product, hydroxyurea, can block SAMHD1 and thereby make the chemotherapy cytarabine more effective. Together with Martin Jädersten, haematologist at Karolinska in Huddinge, an academic study was designed for patients with AML where hydroxyurea was added to the standard treatment in order to enhance the effect of cytarabine.
“The results from our study are very promising. All patients have had an
excellent response to the treatment and the addition of hydroxyurea has been
well tolerated. We have also been able to demonstrate in the laboratory that
the combination gave a higher concentration of active cytarabine within the
leukaemia cells and that the leukaemia cells were killed more efficiently,”
says Martin Jädersten.
It is not uncommon that it takes more than 15 years to develop a new drug
and it is also not uncommon for the lifespan of a medicine to be shorter than
the aforementioned 15 years. This entails high costs and causes the medicines
to be expensive. For Herold and Jädersten, it has only taken five years from
discovery to publication of a clinical study.
“Thanks to reusing an existing and proven drug that is already on the
market, the additional cost per patient will be a couple of hundred kronor,
i.e., the same as a pack of over-the-counter pain killers. It also makes the
treatment available in less resourceful countries worldwide. Hydroxyurea has
previously been used in leukaemia to slow disease progression, but we are now
using it for a new purpose - as a modern precision medicine,” says Nikolas
The study is the result of a successful collaboration between the Theme
Children and Theme Cancer at Karolinska University Hospital, but also of a
close collaboration with several units at Karolinska Institutet, including the
Science for Life Laboratory. The study is now published. It is a successful
example of translational research where a clinical question from the hospital's
everyday life, in this case treatment failure, is taken to the research
laboratory where the cause is mapped and strategies are developed, and
subsequently shown with clinical studies that the standard treatment can be
The study has been published in the Journal of Internal Medicine. The next
step is to recruit an additional 60 patients across the country to the phase 2
part of the study. The authors hope that an addition of hydroxyurea may become
part of the standard treatment against AML as early as within the next few