Autologous stem-cell transplant may help as rescue therapy in refractory Crohnâ??s

Last Updated: 2017-04-27

By Joan Stephenson

NEW YORK (Reuters Health) - Autologous hematopoietic stem-cell transplantation (HSCT) as salvage therapy can benefit patients with refractory Crohn’s disease, although relapse frequently occurs within five years, new research shows.

The therapy “can effect a change in the course of a refractory process in 80% of patients, though it does not represent a cure, since retreatment is needed in the course of the treatment,” researchers from the Hospital Clinic de Barcelona, Spain, note in their report in the Journal of Crohn’s and Colitis, online April 13.

Most of the patients who experienced relapse after HSCT regained responsiveness to conventional treatment, such as anti-TNF therapy.

However, HSCT is associated with a significant risk of adverse events, including death, and “extraordinary and specific measures” in experienced centers are important to reduce these risks, the researchers said.

In the prospective single-center study, 29 patients with refractory Crohn’s disease (median age, 28.8 years) underwent autologous HSCT between 2007 and 2015. Patients were monitored for up to five years, with a median follow-up of 12 months.

Clinical response was defined as a decrease of 100 or more points in the Crohn’s Disease Activity Index (CDAI) from baseline, and clinical remission as a CDAI score of less than 150. Disease activity was also assessed with colonoscopy and/or MRI at defined intervals and at other times if relapse was suspected.

The proportion of patients with clinical and endoscopic relapse-free survival - those with a CDAI score of less than 150 and a Simple Endoscopic Activity Score (SES-CD) of less than 7 without treatment - was 61% at one year, 47% at three years and 15% at five years.

Fifteen of the patients experienced clinical and/or endoscopic relapse after a median of 53.1 weeks and were retreated (all but one with anti-TNF, with or without immunomodulators). Twelve of the 15 (80%) responded to therapy and achieved clinical remission.

Of 20 patients who underwent colonoscopy at month 12, 13 (65%) had mucosal healing (defined as a global SES-CD of less than 7, and with no segment score of 4 or more, which should rule out large ulcers). Eight patients (one of whom was receiving anti-TNF therapy after relapse) had a SES-CD score of 0.

Although most patients experienced relapse within five years after HSCT, the researchers noted that the “great majority of very refractory patients” - up to eight out of 10 - regained responsiveness to drug treatment and experienced clinical remission.

“Our data show that this therapy affords significant and durable benefit in the majority of these patients who were unresponsive to all available medical options, although it carries a significant toxicity,” they write.

The most frequent long-term adverse events were associated with viral infections, including death of one patient from systemic cytomegalovirus infection (CMV) two months after transplantation.

“This study supports the findings of the ASTIC randomised clinical trial in showing that immunoablation and autologous haematopoietic stem cell transplantation can achieve clinical improvement as rescue therapy for the small number of patients with Crohn’s disease who have failed conventional therapies,” Dr. Christopher J. Hawkey, of the Nottingham Digestive Diseases Biomedical Research Centre in the U.K, told Reuters Health by email.

Thirteen of the patients in the current study were treated within the ASTIC trial.

Although most patients relapse with time, as they had in the ASTIC trial, they seem to regain responsiveness to conventional therapies they had previously become resistant to, noted Dr. Hawkey, who led the ASTIC trial, but was not involved in the current study.

“Nevertheless, haematopoietic stem-cell transplantation is a dangerous therapy that confers a measurable risk of septic complications and death, so it is not a treatment that is ready for prime time,” he cautioned.

Further work with lower-intensity regimes that may be safer “may generate results that justify extension to a wider group of patients,” he said.

Dr. Elena Ricart, the study’s corresponding author, did not respond to requests for comment by press time.

The study had no commercial funding, and the authors reported no disclosures.

SOURCE: http://bit.ly/2oF0Liv

J Crohns Colitis 2017.