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More than 25 million Americans have limited English proficiency (LEP) and are more likely than English-proficient (EP) patients to have poor health literacy, not understand their diagnosis, or experience complications from adverse drug effects. Hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure for a variety of malignant and non-malignant diseases. However, HSCT requires prolonged hospitalization and excellent medication adherence to achieve good outcomes. Communication barriers between providers and LEP families of pediatric HSCT patients may further complicate this process and negatively affect clinical outcomes. The objectives of this study were to compare HSCT outcomes of Hispanic pediatric patients with LEP and EP families. Outcomes included overall survival, relapse, length of hospitalization, frequency of re-hospitalization and post-transplant complications including infections and graft-versus-host disease (GVHD). We hypothesized that LEP would be associated with worse outcomes. We conducted a retrospective review of Hispanic or Latino pediatric patients receiving HSCT at Duke University from January 1, 2000 through March 15, 2019. Patients and families were identified as LEP or EP based on clinicians' notes, social work documentation or the signature of a Spanish interpreter on treatment consents. A total of 84 Hispanic/Latino patients were identified with 53 (63.1%) having LEP. There were no significant differences in age at transplant, sex, and race between these groups. Donor types, graft sources, and diagnoses were similar with the exception of more genetic diagnoses in the EP group (32%) than LEP (13%). The cumulative incidence of relapse, neutrophil engraftment, and acute GVHD were similar in both groups, as were the frequency of post-transplant infection and readmission. LEP patients were hospitalized on average 13 days longer than EP patients (Figure 1, p=0.06) and were more likely to have pre-transplant CMV reactivity (66%) than EP patients (30%, Figure 2, p=0.001). Overall survival was lower in LEP than EP but was not statistically significant (Figure 3). Multivariable Cox modeling suggested a potentially higher risk of death in LEP vs EP (hazard ratio=1.56, 95% CI: 0.38, 6.23). Spanish-speaking patients with LEP undergoing HSCT may be at risk for prolonged hospitalization and are more likely to have pre-transplant CMV reactivity. These factors are known to be associated with post-transplant complications and death. Our results suggest LEP families are at higher risk for poor HSCT outcomes. Further study is warranted in a larger cohort. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 10 7 /kg (range, 4.6 to 27.9) and CD34 + dose of 3.1 × 10 5 /kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor. [ABSTRACT FROM AUTHOR]

DUOC-01 is a cord-blood derived, macrophage-based cell therapy product, developed by our group to treat demyelinating conditions of the central nervous system. Recently, we demonstrated that DUOC-01 accelerated remyelination, decreased gliosis, and reduced cellular infiltration in the corpus callosum of immune-incompetent mice treated with cuprizone. To explore the mechanism and investigate whether DUOC-01 will be effective in other experimental models of demyelination, we tested DUOC-01 in lysophosphatidylcholine (LPC) mediated demyelinated murine organotypic cerebellar brain slices and a mouse model of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. In the cerebellar brain slices, we found that DUOC-01 enhanced remyelination, reduced gliosis, and promoted the proliferation of oligodendrocyte progenitor cells in brain slices demyelinated by LPC compared to the untreated control samples. When we injected DUOC-01 cells into the cerebrospinal fluid of mice immunized for EAE, we found decreased severity of clinical disease compared to the vehicle injected control. Currently we are analyzing single cell sequencing data to determine various populations present in DUOC-01 cultures and to understand the functional pathways responsible for promoting remyelination and reducing neuroinflammation. Overall, our data suggest that DUOC-01 could be beneficial in treating diverse neurological conditions with demyelination. [ABSTRACT FROM AUTHOR]