Gut Decontamination In Pediatric Allogeneic Hematopoietic

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.

Inclusion Criteria:

- Eligibility Criteria for Patients Undergoing Allogeneic HSCT

- Recipient of 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1) matched bone marrow
allogeneic hematopoietic stem cell transplantation (HSCT) OR 4/6, 5/6 and 6/6
(HLA-A, -B, -DR) matched cord blood allogeneic HSCT.

- Participants may have underlying malignant or non-malignant hematologic disease,
except for primary immunodeficiency, as the indication for their allogeneic HSCT.
Patients with immune dysregulation such as familial or secondary hemophagocytic
lymphohistiocytosis (HLH) are eligible.

- Participants must may receive either a myeloablative or
non-myeloablative(reduced-intensity) conditioning regimen. Anti-thymocyte
globulin (ATG) in the conditioning regimen is permitted.

- Graft-versus-host disease (GVHD) prophylaxis with any of the following agents:
calcineurin inhibitor, and short-course methotrexate, with or without steroids,
mycophenolate mofetil, and sirolimus.

- Age ≥ 4 years old and toilet-trained. Participants must be able to deposit stool
samples directly into stool collection containers. Stool specimens from diapers
are difficult to obtain and are prone to more sampling error, particularly for
loose or liquid stools which are common in the peri-transplant period.

- Lansky/Karnofsky performance status ≥60% (see Appendix A)

- Ability to understand and/or the willingness of their parent or legally
authorized representative to sign a written informed consent document

- Eligibility Criteria for Healthy Bone Marrow Donors

- Healthy individuals, ages ≥ 4 years and toilet-trained, who have been identified
by BCH or DFCI providers as 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1 matched
bone marrow donors for transplantation will also be eligible to participate in
this study.

Exclusion Criteria:

- Patients undergoing allogeneic HSCT for correction of a primary immunodeficiency
disorder (e.g. SCID).

- Patients with age ≤ 10 years undergoing HSCT with a matched sibling donor. These
patients are at very low risk of acute GVHD and do not receive gut decontamination per
our institutional standard practice.

- Participants receiving GVHD prophylaxis with drugs other than calcineurin inhibitors,
methotrexate or steroids.agents listed above (e.g. abatacept).

- History of allergic reactions attributed to oral vancomycin or oral polymyxin B.

- Participants undergoing active therapy for immune-mediated or infectious colitis upon
admission for allogeneic HSCT.

- Participants receiving antibiotic therapy for treatment of a bacterial infection or
bacterial prophylaxis upon admission for allogeneic HSCT. Use of any agent (e.g.
sulfamethoxazole/trimethoprim) for prophylaxis of Pneumocystis jirovecii pneumonia is
permitted. Concurrent use of anti-fungal and anti-viral therapies is also permitted.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements.