Treosulfan conditioning for CGD stem cell transplants

In the few last years, there has been increasing interest in the use of reduced intensity conditioning regimens for haematopoietic stem cell transplant (HSCT) in patients with CGD. These regimens cause minimal toxicity while achieving high rates of cure, even in high-risk patients who are very sick at the time of the transplant, due to uncontrolled infections or damage caused by chronic inflammation.

Following the study of Dr. Tayfun Gungor et al published in the Lancet in 2015, using low dose Busulfan, there has been another study published in Blood in May 2016 using a different chemotherapy agent, Treosulfan.  Treosulfan destroys the patient’s bone marrow to create some space where the new donor cells can engraft. It has been increasingly used as one of the main conditioning agents for HSCT in children in some European and US centres. It has low-toxicity, but long-term effects are not well documented because of the relatively recent introduction of this drug in conditioning for HSCT.

This study, named “Treosulfan based conditioning for allogeneic HSCT in children with Chronic Granulomatous Disease: a multicentre experience” by Dr. Beatriz Morillo-Gutierrez et al. was a retrospective analysis involving 16 centres from 9 countries worldwide (United Kingdom, Germany, Belgium, Poland, Czech Republic, Italy, Israel, United States, and Australia). It was carried out on behalf of the Innate Error Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (ESBMT) under the lead of Dr. Mary Slatter from the Great North Children’s Hospital in Newcastle-Upon-Tyne (UK).

It included 70 paediatric patients with CGD, so it is the largest study of this kind published so far. The aim was to determine the outcome of a Treosulfan-based conditioning for patients with CGD. Even though most of the patients had high-risk characteristics, the results were excellent.  There was an overall survival of 91.4%; 6 of the 70 patients died after the transplant. The event-free survival (EFS) that is, the alive patients who did not require another procedure such as a second transplant or donor stem cell top up infusions was 81.4%. Most patients were cured of the disease.

In summary, this agent can be used safely for HSCT in children with CGD, even with high-risk clinical features, achieving excellent survival with high curative rates. The results of this study are an important contribution to the field and will help in the decision making process for physicians, patients and their families when facing a transplant. It will encourage further investigations to determine the long-term effects and comparisons with other agents such as low-dose Busulfan.

Dated July 2016