Tailored doses of cytostatic improve survival rate

October 23, 2013

Researchers at Karolinska Institutet in Sweden, and colleagues at University Children's Hospital Zürich in Switzerland have managed to improve cytostatic therapy for children with the chronic immune deficiency disorder granulomatous disease prior to stem cell transplantation. By tailoring doses of the cytostatics administered before the transplantation, the researchers achieved a higher rate of survival with minimal adverse reactions. Now more patient groups are to undergo the same therapeutic strategy.

The results, which are presented in the scientific journal The Lancet, are based on a clinical study conducted at 16 hospitals around the world. Chronic granulomatous disease (CGD) is a rare in children that causes recurrent, often difficult-to-treat bacterial and fungal infections and non-bacterial inflammations of the inner organs, which sometimes develop into tumour-like nodules of inflammatory tissue known as granuloma. By monitoring patients with this disease, the researchers conducting the study developed a protocol for optimising preparatory treatment with cytostatics (cancer drugs) prior to . Careful sampling allowed the doses to be adjusted and optimised for each patient, a procedure that resulted in much better and minimal adverse reactions.

"We can now present a survival rate of 93 per cent, and that with available cytostatics rather than a new drug," says research team member Moustapha Hassan, Professor of transplantation research at Karolinska Institutet's Department of Laboratory Medicine. "This is a terrific result! Particularly so given that its babies that we can now help."

Stem is the only treatment method available today for CGD, and is usually preceded by a course of cytostatic drugs to help the body accept the transplantation. However, one problem is that excessive doses of cytostatics can harm the recipient's organs, leading to complications such as central nervous system damage and infertility, while insufficient doses can cause the patient's body to reject the transplanted stem cells.

"Babies are extremely sensitive to cytostatics, which makes it especially important to find the right dose for each individual patient," says Professor Hassan. "This weve managed to do by monitoring the concentration of cytostatics in their blood and adjusting the dose accordingly to obtain optimal levels for maximal effect and minimal toxicity."

The study involved pre-treating the patients with high doses of the cytostatic fludarabine combined with the immunosuppressive drug anti-T-lymphocyte globulin; they were also given lower doses of a cytostatic called busulfan, levels of which were regularly measured in the patients' blood, allowing the dosages to be adjusted to obtain the desired amount. Because the metabolism of and variations in exposure to busulfan are greater in children than in adults, the researchers consider it imperative to monitor blood levels of the drug.

"Our aim is for tailored treatments to one day become standard practice, which will result in higher survival rates and improved quality of life; our results are so good that we have now begun a similar dose study using the same 'old' cytostatics on patients with leukaemia," says Professor Hassan, who is also especially appreciative of the years of support given to this research by the Swedish Cancer Society and the Swedish Childhood Cancer Foundation.

He hopes that the technique can eventually be used in all drug-based therapies to optimise efficacy for individual patients.

Explore further: Antibodies from rabbits improve survival and relapse outcomes of leukemia and myelodysplasia

More information: 'Reduced-intensity conditioning and HLA-matched haematopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study', Tayfun Güngör, Pierre Teira, Mary Slatter, Georg Stussi, Polina Stepensky, Despina Moshous, Clementien Vermont, Imran Ahmad, Peter J Shaw, José Marcos Telles da Cunha, Paul G Schlegel, Rachel Hough, Anders Fasth, Karim Kentouche, Bernd Gruhn, Juliana F Fernandes, Silvy Lachance, Robbert Bredius, Igor B Resnick, Bernd H Belohradsky, Andrew Gennery, Alain Fischer, H Bobby Gaspar, Urs Schanz, Reinhard Seger, Katharina Rentsch, Paul Veys, Elie Haddad, Michael H Albert and Moustapha Hassan, The Lancet, Early Online Publication, 23 October 2013, DOI: 10.1016/S0140-6736(13)62069

Related Stories

Lifetime of transplanted kidneys can be prolonged

September 10, 2013

The drug Belatacept, which the Medical University of Vienna – represented by Ferdinand Mühlbacher, Head of the University Department of Surgery and the immunologist Thomas Wekerle – was greatly involved in the development ...

Recommended for you

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.