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Study identifies link between gut bacteria, post-SCT survival

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June 25, 2014

The variety of bacteria found in the gastrointestinal tracts of patients who undergo allogeneic stem cell transplant may help predict post-transplant survival, according to study results.

Prior research has demonstrated that the intense treatment involved with allogeneic stem cell transplant can damage the transplant recipient’s gut microbiota, reducing its overall diversity and increasing the likelihood of post-transplant complications. However, the question of whether gut bacteria could predict survival among transplant recipients had not been answered, according to background information provided in the study.

The current analysis included 80 patients who underwent allogeneic stem cell transplant.

Ying Taur, MD, MPH, of the Lucille Castori Center for Microbes, Inflammation and Cancer at Memorial Sloan Kettering Cancer Center, and colleagues analyzed fecal specimens collected from all patients within 7 days of stem cell engraftment.

Researchers characterized bacterial 16S rRNA gene sequences and used the inverse Simpson index to estimate microbial diversity. Results showed 26 patients (32.5%) had high gut microbiota diversity, 20 (25%) had intermediate diversity and 34 patients (42.5%) had low diversity.

Follow-up continued for up to 3 years or patient death.

Results showed levels of microbiota diversity correlated with survival outcomes. Researchers reported 3-year OS of 36% among those with low gut bacteria diversity, 60% among those in the intermediate diversity group and 67% among those in the high diversity group (P=.019).

After researchers adjusted for other clinical predictors, they determined low gut microbiota diversity was significantly associated with transplant-associated mortality (adjusted HR=5.25; P=.014).

“These results further underscore the significance of the gut microbiota in allogeneic stem cell transplantation,” Taur said. “A major question is whether we can improve outcomes by preserving diversity within the gut microbiota. One possible strategy is to find ways to perform transplants in a manner that minimizes damage to the gut microbiota. Another approach would be to replenish the gut with beneficial microbes that are lost after this procedure is performed. We hope that this study will inspire additional research that will further examine the role and importance of the gut microbiota to stem cell transplant outcome.”

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
Harry S. Jacob

Harry S. Jacob

A major role for intestinal homeostasis in prognosticating morbidity severity and/or mortality following allogeneic stem cell transplantation is further validated by just-published data from University of Chicago investigators (Nalle SC. Sci Transl Med. 2014;6:243ra87). Damage to the intestinal barrier from chemotherapy or radiotherapy was shown critical in causing severe/fatal graft-versus-host disease in major histocompatibility complex (MHC)-matched animals. Moreover, recipient natural killer (NK) cells ameliorated disease by inhibiting aggressor donor lymphocytes. Unfortunately, NK cells also are damaged by intense myeloablation. That flooding of bacterial products through the damaged intestinal epithelium is the trigger for catastrophic GVHD was implicated in that parenteral infusion of bacterial lipopolysaccharide replaced the need for gut microflora in their model. These results inform early studies that (1) germ-free animals do not develop GVHD; (2) that manipulation (sterilization of meals) was thought by E. Donnall Thomas, MD, beneficial in diminishing GVHD in his early transplanted patients; and (3) certainly that increasing recent efforts to reduce preparatory regimens is most welcome. Perhaps auto transfusion of stored recipient NK cells might also be a worthwhile GVHD prophylactic in the future.

Harry S. Jacob, MD, FRCPath(Hon)
HemOnc Today Founding Chief Medical Editor
Consulting Editor, Hematology

Disclosure: Jacob reports no relevant financial disclosures.