Autologous stem-cell transplant may have benefits in refractory Crohn's

Last Updated: 2017-04-17

By Reuters Staff

NEW YORK (Reuters Health) - Autologous stem-cell transplantation (ASCT) is associated with clinical and endoscopic benefits in patients with refractory Crohn's disease, but with a significant risk of adverse events, according to data from the ASTIC trial.

One-year results from ASTIC showed no benefit of ASCT versus conventional care in patients with refractory Crohn's disease when the primary endpoint was steroid-free clinical remission for three months with no endoscopic or radiological evidence of intestinal inflammation.

Now, Dr. James O. Lindsay from Barts and the London School of Medicine and Dentistry and colleagues report clinical outcomes after one more year, including 17 patients from the conventional-care group who received ASCT at the end of ASTIC.

At baseline and one year later, data were available for 40 and 38 patients, respectively, in the combined group, the team reports in The Lancet Gastroenterology & Hepatology, online April 6.

Thirteen of 34 patients with available data (38%) achieved steroid-free clinical remission for three months, 12 of 34 patients (35%) were in remission for three months off all medical therapies and 16 of 37 patients (43%) were in steroid-free remission at one year.

Half of the patients achieved complete endoscopic healing, 31 of 38 patients (82%) achieved partial endoscopic healing and 18 of 38 patients (47%) were free of intestinal ulceration on endoscopic and radiological assessment at one year.

ASCT brought significant improvements in clinical disease activity and quality of life, as measured by Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire and European Quality of Life Visual Analog Scale.

Shorter time from diagnosis to ASCT and lower baseline CDAI were independently associated with steroid-free remission for at least three months, whereas no baseline factors were independently associated with complete endoscopic healing or with being free of all active disease at one year in multivariate analyses.

Nearly 60% of patients undergoing ASCT experienced serious adverse events, more than half of which were designated as related to treatment. The most frequent serious adverse events related to treatment were infectious.

Smoking and perianal disease at baseline were independently associated with an increased number of serious adverse events.

“These data show significant benefit from hematopoietic stem-cell transplantation (HSCT) in terms of steroid-free clinical remission, enhanced quality of life, and mucosal healing,” the researchers conclude. “The large number of serious adverse events suggests that this treatment strategy should only be considered in patients who are refractory to biological therapies.”

“Identification of factors that predict both benefit and harm will be invaluable in the design of future trials,” they add. “Such trials should assess whether the use of low-intensity mobilization and conditioning regimens can maintain the observed benefit while reducing the risk of HSCT.”

“Autologous HSCT, done with the ASTIC approach, was not a cure,” write Dr. Richard K. Burt from Northwestern University Feinberg School of Medicine, in Chicago, and colleagues in a linked editorial. “It did, however, define the maximum limit of combined mobilization and transplantation cyclophosphamide dose, and resulted in significant improvements in patients with refractory Crohn’s disease.”

“Further investigation of autologous HSCT to define the optimal candidate, mobilization, regimen, and standard of care during and after transplantation should continue within experienced centers,” they conclude. “Before initiation of another randomized trial, further phase 1–2 studies of modified mobilization and conditioning regimens should be performed to minimise unique Crohn’s disease toxicity while also optimizing efficacy.”

Dr. Lindsay did not respond to a request for comments.

SOURCE: http://bit.ly/2oOQPq4 and http://bit.ly/2ptcdiv

Lancet Gastroenterol Hepatol 2017.