BY PAUL KLEUTGHEN Several studies have been published over the past few years about the beneficial impact of fecal microbiota transplants (FMTs) in the treatment of chronic Clostridium difficile (C diff) and Crohns disease. The Journal Blood recently published an article about a small scale FMT-study done by Kazuhiko Kakihana, MD, PhD, of the hematology division at Tokyo Metropolitan Cancer and Infectious Diseases Center at Komagome Hospital, and colleagues, in patients with acute Graft versus Host Disease (GvHD) following allogeneic (donor) stem cell transplant. GvHD is the leading cause of mortality following allo transplants. Typically, patients are treated with glucocorticoids as first line therapy, but there is little available in the way of second line therapy. Only about half the patients treated with steroids respond favorably to treatment of acute GvHD. Two rounds of FMTs were administered roughly three months after allo-SCT in this study. Although the study was small (4 patients), three patients with acute steroid resistant GvHD and one with acute steroid dependent GvHD, the results are exciting enough to merit further study. Three patients achieved a complete response and the fourth achieved a partial response. The patients with steroid resistant cases improved rapidly a few days following treatment. All four had been experiencing infectious complications at the time of transplant. So what are microbiota? Microbiota are bacteria that live inside us and it is estimated that inside the human body there are 10 times more bacterial cells than human cells. Microbiota in the gut can be disrupted by a variety of reasons (e.g. antibiotic use) and this disruption may result in the C diff infection, a bacterium that can cause diarrhea and serious infection of the colon. Chances are pretty good that all of us, ex or current, transplant patients have at least heard of C diff, if not experienced it first-hand. Treatment of C diff is intensive, unpleasant and expensive. About 2/3 of patients have a recurrence of C diff after the third round of antibiotic treatment and the cost of treatment, at the national level in the US, is measured in the billions of dollars. But um...how does one actually do a fecal microbiota transplant? Dr. Ari Greenspan, Mount Sinai Hospital, explains this in a recent issue of Infectious Disease News:
To perform an FMT, a healthy stool sample gets diluted in saline and then infused into a patients colon during a colonoscopy and that is basically it. Critically though, the stool sample must come from a qualified and thoroughly screened donor in the same manner as a blood donor, but with a GI questionnaire relating to gastroenterology health and history such as ulcers, colon cancers and polyps.
In the Japanese study mentioned earlier, the donors were patients spouses or relatives who had passed screening for transmittable diseases. What is the future of FMTs? Dr. Greenspan indicates:
Clinical trials are currently underway in a variety of research in these areas [autism, fatty liver disease, diabetes, IBD, and even obesity] as well as is the fecal matter delivery system itself a so-called Poop Pill is already in the works. So stay tuned as we unlock the power of poop.
Dr. Kakihana, and colleagues, wrote Fecal microbiota transplantation was safely performed in stem cell transplant patients and offers promise as a potential treatment option for acute GvHD. Further evaluation to confirm the safety and efficacy of fecal microbiota transplantation for acute GvHD is warranted. Despite the very small number of patients, our results are highly suggestive for elucidating the associations between microbiota and human immunity.
about the author
I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.