Treatment for acute leukemia involves repeated exposure to chemotherapies and associated antibiotics to treat and prevent infections in the immunosuppressed state. We have recently shown that repeated therapies result in an intestinal microbial community with lower resilience that is more susceptible to perturbations as treatments progress. Following cessation of treatments, the microbial community recovers its diversity, but it remains compositionally different from its original configuration. Our group, in collaboration with Dr. Armin Rashidi and others in the Division of Hematology, Oncology, and Transplantation, is working to understand the clinical and ecological significance of these changes.
We have also identified specific states during treatment in which certain species of potential pathobionts - commensal bacteria that may become detrimental to the host in an imbalance, dysbiotic state - become dominant. We are working to characterize these states and evaluate the mechanism(s) by which keystone species in these states influence patient outcomes.
In August 2018, we received funding for this work through the Chainbreaker mechanism from the Masonic Cancer Center. In addition to other on-going projects, an interventional trial to supplement the intestinal microbiota using restorative microbiota therapy during leukemia treatments is planned.
Rashidi A, Maeser D, Kaiser T, Ebadi M, Rehman TU, Holtan SG, Weisdorf DJ, Khoruts A, Staley C. 2020. British Journal of Haematology. Microbiome swings with repeated insults. doi:10.1111/bjh.16509
Rashidi A, Herman A, Staley C, Blazer BR, Weisdorf DJ. 2019. British Journal of Haematology. An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease. doi:10.1111/bjh.16458
Rashidi A, Kaiser T, Graizer C, Holtan SG, Rehman TU, Weisdorf DJ, Dunny G, Khoruts A, Staley C. 2019. Cancer. Gut dysbiosis during anti-leukemia chemotherapy versus allogeneic hematopoietic cell transplantation. in press.
Rashidi A, Zhigang G, Kaiser T, Manias DA, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Dunny GA, Staley C. 2019. Vancomycin-resistance gene cluster, vanC, in the gut microbiome of acute leukemia patients undergoing intensive chemotherapy. Plos One. 14(10), e0223890 doi:10.1371/journal.pone.0223890
Rashidi A, Kaiser T, Graizer C, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Staley C. 2019. Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy. Leukemia. doi:10.1038/s41375-019-0547-0
Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Holtan SG, Rehman T, Wasko J, Weisdorf DJ, Dunny G, Khoruts A, Staley C. 2019. Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia. Sci. Rep. 9(1), 6083. doi:10.1038/s41598-019-42652-6
Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Ur Rehman T, Holtan SG, Weisdorf DJ, Knights D, Khoruts A, Staley C. 2019. Gut dysbiosis increases gut barrier damage during anti-leukemia chemotherapy: implications for acute graft-versus-host disease. Biol. Blood Marrow Transplant. 25(3), S142-143. doi:10.1016/j.bbmt.2018.12.433
Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Ur Rehman T, Holtan SG, Weisdorf DJ, Knights D, Khoruts A, Staley C. 2019. Outpatient-to-inpatient transition causes marked dysbiosis in allogeneic hematopoietic cell transplantation recipients. Biol. Blood Marrow Transplant. 25(3), S47. doi:10.1016/j.bbmt.2018.12.124
Rashidi A, Kaiser T, Holtan S, Weisdorf D, Khoruts A, Staley C. 2018. Pre-transplant recovery of microbiome diversity without recovery of the original microbiome. Bone Marrow Transplant. 54, 1115-1117. doi:10.1038/s41409-018-0414-z