23 August 2022

Hope for leukaemia patients through discovery at Karolinska University Hospital



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 Herold.

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 improved.

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 years.

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