Zurich researchers have found a new treatment approach which they hope will help young leukaemia patients who don’t respond to conventional therapies.
Leukaemia is a malignant disease of the blood and bone marrow, which accounts for a third of childhood cancers.
Despite great progress in leukaemia treatment, recurrence of the disease is common. Treatment in these cases is often challenging because of the resistance of the cancer cells to the drugs currently available. Modern treatment processes are still very long and hard for the affected youngsters.
The Zurich University Children’s Hospital team, led by Jean-Pierre Bourquin, conducted their research around acute lymphoblastic leukaemia (ALL), the most frequently occurring form, of which there are up to 70 cases a year in Switzerland and up to 1,000 cases in Europe.
“By learning in international cooperative studies how to combine available chemotherapeutic agents, we have made incredible progress with the treatment of childhood leukaemia in the last 30-40 years, so that we can now cure more than 80 per cent of cases of ALL,” Bourquin told swissinfo.ch.
“But we still have a sub-group of patients that are resistant to whatever we do for them and we urgently need new kinds of treatments.”
These can be first timers or relapsed patients, he added.
Bourquin and his group investigated a substance called obatoclax mesylate and found a positive result: it actually lowered resistance when used in conjunction with chemotherapy.
This has to do with what is called programmed cell death. Cells can, in certain situations, induce their own suicides.
“This is absolutely critical for us to survive. Think about an infection: you get a virus that will trigger your blood cells to fight, they will proliferate do the job, but then you have to get rid of them or you will have leukaemia,” Bourquin said.
“So you have a mechanism in place to kill them: this is a programmed cell death, which carries this out in an absolutely timed manner and triggers the system to clean the fragments of dead cell bodies away.”
Chemotherapy normally triggers the cancerous cells to commit suicide. But in patients with a resistance to this treatment this doesn’t happen.
However, it was found that a low dose of obatoclax mesylate could influence the mechanism that controls programmed cell death, thus restoring the response to conventional anti-leukaemia drugs when given in combination.
“The use of a small dose of this compound, which is not toxic at this dose, dramatically increased the response to the usual type of chemotherapeutic agents we use for children,” Bourquin said.
What is more, the substance worked for several types of chemotherapy agents.
The results of the study, which were obtained with a new type of experimental system, in which leukaemia cells from the most resistant patients could be studied directly in mice, have been published in the latest edition of the Journal of Clinical Investigation.
“Based on our results we are very confident that this approach will be very useful in designing new experimental therapy elements,” Bourquin commented.
New therapy hope
The Harvard-educated medic, who is both an attending paediatric oncologist at the children’s hospital and an expert in molecular and cell biology, said that specialists in leukaemia were convinced that obatoclax mesylate was worth investigating for clinical development.
Bourquin has already designed a clinical protocol to test the substance further. Key will be checking its safety before it is given to children and finding at which dose children would respond.
“We hope that within 18 months we will be able to provide a small one-week treatment elements to patients with refractory [resistant] leukaemia,” he told swissinfo.ch.
However, he cannot make big promises at this stage. “It will take several steps and constructive collaborations between European and North American centres before we really know how to use this type of compound in patients to achieve the maximum and best curative effect,” he said.
Nevertheless the discovery provides hope. “It’s a very promising way to achieve progress more rapidly for this group of patients really needing new options,” said the oncologist.
Isobel Leybold-Johnson in Zurich, swissinfo.ch
The study was carried out by a team at Zurich University’s Children’s Hospital, which was led by Jean-Pierre Bourquin and included Beat Bornhauser, senior scientist, and PhD student Laura Bonapace.
It is published in the April edition of the renowned The Journal of Clinical Investigation and is already available online.
Leukaemia is a cancer of the blood or bone marrow, characterised by an abnormal proliferation of white blood cells (leukocytes).
Acute leukaemia is characterised by the rapid increase of immature blood cells, which makes the bone marrow unable to produce healthy blood cells. Immediate treatment is needed as the rapid progression and accumulation of the malignant cells can spill over into the bloodstream and spread to other body organs.
Chronic leukaemia involves the excessive build up of relatively mature, but still abnormal, white blood cells. It can take time to progress and mostly occurs in older people.
Around 870 people are diagnosed with leukaemia in Switzerland annually, making up around 2% of all cancers. Almost half of those affected are 70 years old or over when diagnosed.
Acute leukaemia is the most common type of cancer among children.
The other type of acute childhood leukaemia, childhood acute myeloid leukaemia, (AML), is similar to AML in adults and can draw on research and development of treatments for adult AML.
(Source: Swiss Cancer League, Jean-Pierre Bourquin)