Hematopoietic cell transplantation (HCT) has become a standard treatment for many adult and pediatric conditions. Emerging evidence suggests that perturbations in the microbiota diversity increase recipients' susceptibilities to gut-mediated conditions such as diarrhea, infection and acute GvHD. Probiotics preserve the microbiota and may minimize the risk of developing a gutmediated condition; however, their safety has not been evaluated in the setting of HCT. We evaluated the safety and feasibility of the probiotic, Lactobacillus plantarum (LBP), in children and adolescents undergoing allogeneic HCT. Participants received oncedaily supplementation with LBP beginning on day − 8 or − 7 and continued until day +14. Outcomes were compliance with daily administration and incidence of LBP bacteremia. Administration of LBP was feasible with 97% (30/31, 95% confidence interval (CI) 83-100%) of children receiving at least 50% of the probiotic dose (median 97%; range 50-100%). We did not observe any case of LBP bacteremia (0% (0/30) with 95% CI 0-12%). There were not any unexpected adverse events related to LBP. Our study provides preliminary evidence that administration of LBP is safe and feasible in children and adolescents undergoing HCT. Future steps include the conduct of an approved randomized, controlled trial through Children's Oncology Group.

The presence of increasing host chimerism or persistent mixed chimerism (MC) after hematopoietic stem cell transplantation for leukemia in children is a predictor of relapse. To reduce the risk of relapse, we prospectively studied post-transplantation chimerism-based immunotherapy (IT) using fast withdrawal of immunosuppression (FWI) and donor lymphocyte infusions (DLI) in children with early post-transplantation MC. Forty-three children with hematologic malignancies at 2 institutions were enrolled prospectively in this study from 2009 until 2012 and were followed for a mean of 42 (SD, 10) months. Twelve patients (28%) were assigned to the observation arm based on the presence of graft-versus-host disease (GVHD) or full donor chimerism (FDC), and 5 (12%) sustained early events and could not undergo intervention. Twenty-six (60%) patients with MC were assigned to IT with FWI, which started at a median of 49 days (range, 35 to 85 days) after transplantation. Fourteen patients proceeded to DLI after FWI. Toxicities of treatment included GVHD, which developed in 19% of patients undergoing intervention, with 1 of 26 (4%) dying from GVHD and 1 (4%) still requiring therapy for chronic GVHD 21 months after DLI. Patients with MC undergoing IT had similar 2-year event-free survival (EFS) (73%; 95% confidence interval (CI), 55% to 91%) compared with patients who achieved FDC spontaneously (83%; 95% CI, 62% to 100%); however, because 50% of all relapses in the IT occurred later than 2 years after transplantation, the EFS declined to 55% (95% CI, 34% to 76%) at 42 (SD, 11) months. There were no late relapses in the observation group. EFS in the entire cohort was 58% (95% CI, 42% to 73%) at 42 (SD, 11) months after transplantation. Evidence of disease before transplantation remained a significant predictor of relapse, whereas development of chronic GVHD was protective against relapse.

Aldrich (2), neuroblastoma (2) and 1 osteopetrosis and 1 medulloblastoma. Norovirus was detected by RNA RT-PCR test of stool performed by Focus Diagnostics, Cypress, Ca. The dose of Nitazoxanide was 100 mg po BID for ages 1 to 4 years, 200 mg po BID for age 4 to 11 years, and 500 mg po BID for greater than 11 years. 1 pt, 33 months post allo HSCT with normal immune studies was not treated as symptoms resolved prior to test result. All other pts clinically responded with improvements in diarrhea, nausea, and abdominal pain in 2-4 days (median 2 days). 3 pts were pre-HSCT on chemo/immunotherapy and 11 were 17 days to 34 months after HSCT. All the treated pts were on immune suppression or chemotherapy. 9 allo HSCT pts were on immunosuppression and 5 of these had GVHD at onset of symptoms. Immune suppression included tacrolimus/solumedrol (3), cellcept/solumedrol (2) plus infliximab (1), tacrolimus (1), cyclosporine (1), tacrolimus/cellcept (1). 3 pts were receiving immunotherapy (1), or chemotherapy for solid tumors (2) prior to planned HSCT. 1 pt was 10 months post auto HSCT. Clearance of stool virus was variable. 2/3 pts treated prior to HSCT became negative on stool study within 5-14 days of treatment (1 unknown duration). Among pts treated after HSCT 4/9 had persistent viral shedding, 2 received drug until death (1 adenovirus, 1 CHF) both were treated greater than 2 months, 3 with GVHD still shed virus after 6 months of treatment, and 4 are off therapy and remain negative for norovirus RNA. 1 auto HSCT pt stopped viral shedding 2 months post starting Nitazoxanide. 2 HSCT pts with clinical resolution but persistent viral shedding stopped treatment and had clinical symptoms return. These pts responded to restarting therapy within 2 days but continue to shed virus. UGI endoscopy/colonoscopy were performed in 5 pts at the time of infection, all showed inflammation/edema but no GVHD was seen on histology. Peripheral blood CD4 counts among those with persistent viral shedding ranged from <50-445/ul and for those that cleared virus 143-1222/ul. Nitazoxanide is effective therapy for norovirus gastroenteritis in immune compromised patients. Therapy needs to be continued until stool RNA studies become negative.

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Background: BK Virus-associated hemorrhagic cystitis (BKHC) has emerged as a serious infection after HSCT, however data in children are limited. Objective: To describe the clinical characteristics, treatment, and outcomes of BKHC in children after HSCT. Patients and Methods: Retrospective review of medical records of children who underwent HSCT at Children's Medical Center Dallas from Jan 1, 2006-July 31, 2011 with evidence of BKHC. Demographic, clinical, microbiologic, management, and outcome data was collected. Results: 20 children (incidence 13%), 9 males, median age 11 y [range 5-18], developed BKHC a median of 15 days [-2 to 57] post autologous (1) and allogeneic (19) HSCT: MRD (6), MUD (6), MMUD (6), syngeneic (1) for ALL (7), AML (4), aplastic anemia (4), and other conditions (5). Conditioning included busulfan/cyclophosphamide/ATG (10), TBI/thiotepa/cyclophosphamide (9), & carboplatin, etoposide, melphalan (1). Only 8 (40%) patients had engrafted and 7 (35%) were receiving systemic corticosteroids at BKHC onset. 7 (35%) patients complained of dysuria; 15 (75%) had moderate to large blood on initial urinalysis, all had BK viruria, 14 (70%) had $ 10 6 BK copies/mL urine. 6 (30%) had BK viremia at HC onset, 16 (80%) developed viremia with median peak BK of 10, 850 copies/mL blood [439-1.5 million] on D+42 (7-91), resolving in 11/16 by D+76 [22-134]. There was no correlation between viruria and viremia at onset (Spearman R 0.41, p 5 0.07). 8 (40%) had abnormal initial ultrasounds (5 echogenic debris/clot, 4 bladder wall thickening). Patients had grade 1 (4), 2 (6), 3 (4), and 4 (6) HC. 14 (70%) patients were already receiving fluoroquinolone prophylaxis at BKHC onset; 17 (85%) patients received Cidofovir at 1 mg/kg 3x/wk (11), 3mg/kg qwk (1), or 5mg/kg qwk (5) for a median of 62 days [1-119]. 6 (30%) patients developed renal insufficiency requiring CVVH, one patient developed Fanconi's syndrome; 2 (10%) had urological interventions for obstruction and bleeding. 7 children died from other causes. Concomitant infections included: bacteremia (5), candidemia (3), peritonitis (2), UTI (2), detectable CMV (5), EBV (2), and adenovirus (4) viremia. Conclusions: Incidence of BKHC was high in our HSCT population, with most children presenting pre-engraftment. Though many had clinical and virological resolution, morbidity was not negligible. Additional data in pediatric BKHC after HSCT is needed to guide optimal treatment guidelines.