Lactobacillus Rhamnosus GG in Reducing Incidence of Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine if hematopoietic stem cell transplant (HSCT) patients treated with a
probiotic (Lactobacillus GG [Lactobacillus rhamnosus GG])-containing diet compared to those
not assigned to receive probiotic have a lower incidence of grade 1 upper gastrointestinal
(GI) or grade 2-4 lower GI acute graft-versus-host disease (GVHD) (aGVHD) using Center for
International Blood and Marrow Transplant Research (CIBMTR) scoring than those not prescribed
a probiotic.

II. To determine if HSCT patients treated with a probiotic-containing diet compared to those
not assigned to receive a probiotic have a: a) lower rate of organ-specific acute aGVHD
(intestinal tract, skin, liver); b) lower rate of moderate or severe chronic GVHD (National
Institutes of Health [NIH] consensus scoring) at 6 months and 1 year post transplant; c)
shorter duration of immunosuppressive therapy (normalized for age and degree of human
leukocyte antigen [HLA] match); d) lower rate of bacterial and/or opportunistic infection.

SECONDARY OBJECTIVES:

I. To determine if allogeneic hematopoietic stem cell patients treated with a probiotic
compared to those not assigned to receive a probiotic have differences in: a) composition and
proportion of the major gut bacterial phylotypes in stool (to be analyzed for changes pre-
and post-initiation of probiotics and for association with development of aGVHD); b) measures
of inflammation as assessed by cytokine or receptor production (interleukin [IL]-6, IL-8,
tumor necrosis factor [TNF]-alpha, TNF-receptor 1, interferon-gamma, IL-2R, IL-10); c)
qualitative measures of immune reconstitution as determined by sequential measurements of
conventional T cells, regulatory T regulatory, B cells and natural killer (NK) cells; d)
antibody class/subclass production; e) biomarkers associated with GVHD-elafin, regenerating
islet-derived 3 alpha (Reg3a), suppressor of tumorigenicity-2 (ST2), hepatocyte growth factor
(HGF); and/or urinary tryptophan metabolites; f) markers of gut barrier function including
blood levels of endotoxin and microbial deoxyribonucleic acid (DNA).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive Lactobacillus rhamnosus GG orally (PO) once daily (QD) for 1 year.

ARM II: Patients receive no intervention.

Inclusion Criteria:

- Able to sign informed consent

- Undergoing allogeneic HSCT from a related or unrelated donor

- Hematopoietic engraftment as evidenced by recovery of the absolute neutrophil count to
greater than 500/mm^3 for > 3 days without filgrastim (G-CSF) support and within 40
days of transplant (i.e. complete blood counts [CBCs] obtained 3 or more days apart
while off of G-CSF must demonstrate an absolute neutrophil count > 500/mm^3); if
absolute neutropenia is not achieved due to a non-myeloablative transplant, the
patient can be enrolled on day +21 to +40

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

- Evidence of GVHD at the time of enrollment as assessed clinically

- Serum creatinine greater than 3.0

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3
times the upper limit of normal

- Total bilirubin greater than 2 times upper limit of normal

- Prior use of probiotics within 3 months prior to enrollment

- Inability to take medications by mouth

- Prior history of inflammatory bowel disease or other chronic diarrheal illness

- Prior history of hypersensitivity to milk proteins

- Active Clostridium difficile infection or on prophylactic or tapering antibiotics for
Clostridium difficile infection