This research study is for participants who are undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and are at risk for developing acute graft-versus-host disease (GVHD). GVHD is a complication of HSCT in which immune cells from the donor cause inflammation and injury to tissues and organs of the HSCT recipient. Vancomycin-polymyxin B (commonly called "vancopoly") is an oral antibiotic that is given to people undergoing allogeneic HSCT as a preventive measure for acute GVHD. This research study is studying the effects of vancopoly on the microorganisms living in the intestine during and after stem cell transplantation.
This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. Pre-clinical studies performed in the 1970's showed that killing all the bacteria in the intestine with oral antibiotics could decrease the risk of acute GVHD following allogeneic HSCT. Based on this observation, many stem cell transplant centers adopted the practice of "gut decontamination" with oral antibiotics as a preventive measure for acute GVHD. There is no standard regimen for gut decontamination between transplant centers, and there are no definitive human studies showing that gut decontamination is beneficial for lowering the risk of acute GVHD. Recent studies in adult patients undergoing stem cell transplant indicate that the types of bacteria living in the intestine can influence bone marrow transplant outcomes such as survival and development of acute GVHD. Some types of bacteria may be protective against GVHD and others may increase the risk of GVHD. Based on this newer research, it is possible that the practice of gut decontamination ("vancopolys") may not be beneficial for HSCT patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
24
Boston Children's Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Gut Microbiome Description
Shannon diversity index (range: 0-6), measured at 2 weeks post stem cell transplant. Shannon diversity is a way to calculate biodiversity in a community, and assumes that all species are represented in a sample and that they are randomly sampled. Shannon Diversity is a measurement sensitive to the loss of rare taxa (34 in the JCI Insight manuscript, Konopinski MK, PeerJ. 2020;8:e9391) and estimates microbial richness (e.g., the number of species) and evenness (e.g., the relative abundance of organisms within a sample). Formula 1: H = -∑\[(pi) \* ln(pi)\], * H: Shannon diversity index (H = 0 indicates that a community has only one species) pi: Proportion of individuals of i-th species in a whole community Formula 2: pi = n / N, * n: individuals of a given type/species * N: total number of individuals in a community
Time frame: 2 Weeks post HSCT
Diarrhea Frequency
The number of daily bowel movements during the first 7 days post-HSCT is charted by floor nurses and/or clinical assistants and will be obtained from within each patient's electronic medical record in PowerChart. Diarrhea frequency is defined the proportion of participants who had greater than 3 bowel movements per day.
Time frame: Participants were followed 7 days after HSCT.
Median Absolute Cell Numbers of T-, B-, NK- and Dendritic Cell Subsets by Flow Cytometry
CD4+ Tregs were defined as CD3+CD4+CD25med-hiCD127lo, CD4+; Tcon as CD3+CD4+CD25neg-lo CD127med-hi, B cells as CD19+, cytotoxic T cells as CD8+, and natural killer cells as CD56+CD3-. Within CD4+ Tregs and CD4+ Tcon, subsets were defined as follows: naive T cells (CD45RO-CD62L+), central memory (CD45RO+CD62L+), and effector memory (CD45RO+CD62L-).
Time frame: Performed at the post-transplant time points (1,2,3,6,9,12 months post-transplant)
Incidence of Acute GVHD (Grade 2-4)
Grade 2 acute GVHD was defined as skin stage 3 or GI stage 1 or liver stage 1. Skin stage 3 was defined as maculopapular rash \>50% of body surface or generalized erythroderma; GI stage 1 was defined as adults: 500 - 1000 mL/day, children: 10 - 19.9 mL/kg/day or nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD; liver stage 1 was defined as bilirubin 2.1-3 mg/dL. Grade 3 acute GVHD was defined as GI stage 2-4 or liver stage 2-3. GI stage 2-4 was defined as \>1001 mL/day (adults), \>30 ml/kg/day(children) or large volume stool with severe abdominal pain with our whiteout ileus or stool with frank blook or melena; liver stage 2-3 was defined as bilirubin 3.1-15mg/dL. Grade 4 acute GVHD was defined as skin stage 4 or liver stage 4. Skin stage 4 was defined as generalized erythroderma with bullous formation and desquamation; liver stage 4 was defined as bilirubin \> 15mg/dL.
Time frame: Each stool collection time point after neutrophil engraftment until day +100
Overall Survival Rate at 12 Months (OS12)
OS12 is the proportion of participants alive at 12 months after study entry.
Time frame: All participants were followed for 1 years after study entry.
Relapse Free Rate at 12 Months
Relapse free rate at 12 months was defined as the proportion of patients surviving without any signs or symptoms of that cancer after 12 months.
Time frame: Patients were followed for 12 months.
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