Subcutaneous Immunoglobulin Replacement Therapy with Hizentra® is Safe and Effective in Children Less Than 5 Years of Age.

BACKGROUND:Hizentra® (IGSC 20%) is a 20% liquid IgG product approved for subcutaneous administration in adults and children 2 years of age and older who have primary immunodeficiency disease (PIDD). There is limited information about the use of IGSC 20 % in very young children including those less than 5 years of age. METHODS:A retrospective chart review involved 88 PIDD infants and children less than 5 years of age who received Hizentra®. RESULTS:The mean age at the start of Hizentra® was 34 months (range 2 to 59 months). IGSC 20 % was administered weekly to 86 infants (two additional infants received twice weekly and three times weekly infusions, respectively) and included an average of 63 infusions (range 6-182) for an observation period up to 45.5 months. Infusion by manual delivery occurred in 15 patients. The mean dose was 674 mg/kg/4 weeks. The mean IgG level was 942 mg/dL while on IGSC 20 %, compared to a mean trough IgG level of 794 mg/dL (p < 0.0001) during intravenous or subcutaneous IgG administration prior to IGSC 20 %. Average infusion time was 47 (range 5-120) minutes, and the median number of infusion sites was 2 (range 1-4). Local reactions were mostly mild and observed in 36/88 (41%) children. No serious adverse events were reported. A significant increase in weight percentile (7 % ± 19.2, p = 0.0012) among subjects was observed during IGSC 20% administration. The rate of serious bacterial infections was 0.067 per patient-year while receiving IGSC 20%, similar to previously reported efficacy studies. CONCLUSIONS:Hizentra® is effective in preventing infections, and is well tolerated in children less than age 5 years

Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD

X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n = 30, 75%) and HLA-mismatched (n = 10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p = 0.01) and 8.2 (CI 2.1-32.7, p < 0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT

Altered Development of NKT Cells, γδ T Cells, CD8 T Cells and NK Cells in a PLZF Deficient Patient

In mice, the transcription factor, PLZF, controls the development of effector functions in invariant NKT cells and a subset of NKT cell-like, γδ T cells. Here, we show that in human lymphocytes, in addition to invariant NKT cells, PLZF was also expressed in a large percentage of CD8+ and CD4+ T cells. Furthermore, PLZF was also found to be expressed in all γδ T cells and in all NK cells. Importantly, we show that in a donor lacking functional PLZF, all of these various lymphocyte populations were altered. Therefore, in contrast to mice, PLZF appears to control the development and/or function of a wide variety of human lymphocytes that represent more than 10% of the total PBMCs. Interestingly, the PLZF-expressing CD8+ T cell population was found to be expanded in the peripheral blood of patients with metastatic melanoma but was greatly diminished in patients with autoimmune disease

Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency

Hematopoietic stem cell transplantation (HSCT) is an effective approach for the treatment of severe combined immunodeficiency (SCID). However, SCID is not a homogeneous disease, and the treatment required for successful transplantation varies significantly between SCID subtypes and the degree of HLA mismatch between the best available donor and the patient. Recent studies are beginning to more clearly define this heterogeneity and how outcomes may vary. With a more detailed understanding of SCID, new approaches can be developed to maximize immune reconstitution, while minimizing acute and long-term toxicities associated with chemotherapy conditioning

Preserving the lighthouses of Martha's Vineyard.

This project prepared for the Martha's Vineyard Historical Society describes the steps needed to preserve the Lighthouses leased by the Society. This evaluation examines preservation against weather, structural failure, erosion, and human tampering. Financing the preservation involves investigating grant studies, enhancing donation expectations and tour profits through advertisement, as well as miscellaneous contributions. Tourists, the local community, and history buffs honor the Lighthouses; a plan for the future of these monuments needs to be established

Transplacental maternal engraftment and posttransplantation graft-versus-host disease in children with severe combined immunodeficiency.

BackgroundGraft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplacental maternal engraftment (TME), the presence of maternal T cells in peripheral blood before transplantation, is detectable in a significant proportion of patients with severe combined immunodeficiency (SCID). Although the presence of TME is associated with a decreased risk of rejecting a maternal graft, it is unknown whether TME plays a role in development of GVHD after HSCT.ObjectiveThe purpose of this study was to determine whether the presence of pretransplantation TME is associated with posttransplantation GVHD in patients with SCID.MethodsThis was an institutional retrospective review of 74 patients with SCID undergoing transplantation between 1988 and 2014. The incidence of acute graft-versus-host disease (aGVHD) was compared in patients with versus those without TME. Confounding variables, such as donor type and conditioning regimen, were included in a multivariate regression model.ResultsTME was identified in 35 of 74 children. Post-HSCT aGVHD developed with an incidence of 57.1% versus 17.9% in those without TME (P &lt; .001). In univariate analysis donor type (mother) and GVHD prophylaxis (T-cell depletion) were also significant predictors of aGVHD. In multivariate analysis TME and chemotherapy conditioning were independent risk factors for the development of aGVHD (relative risk, 2.75, P = .006 and relative risk, 1.42, P = .02, respectively).ConclusionTME independently predicts the development of posttransplantation aGVHD, even when controlling for donor type and conditioning used. The presence of TME should be considered when assessing the risk of aGVHD in patients with SCID and designing the approach for GVHD prophylaxis

Surface stoichiometry of La0.7Sr0.3MnO3 during in vacuo preparation; A synchrotron photoemission study

We present a study of the surface stoichiometry and contamination of La0.7Sr0.3MnO3 thin films following exposure to air and subsequent in vacuo preparation. Samples were studied using both soft X-ray synchrotron photoemission (hv = 150 to 350 eV) and traditional Mg-K alpha XPS (hv = 1253.6 eV) whilst annealing incrementally to approximate to 510 degrees C in low pressures of O-2. In all cases, a Mn depleted and Sr rich surface oxide layer is observed, it is of reduced crystalline quality and is charge depleted. This surface layer is weakly affected by subsequent annealing, and is partially reversed by annealing in higher O-2 pressure. Surface carbon contamination is incrementally removed by annealing at increased temperatures, and at 270 degrees C, it is reduced to approximate to 0.4% of the topmost unit cell. The modification of the surface stoichiometry and electronic properties is consistent with the reported loss of magnetic properties in thin LSMO films. (C) 2012 Elsevier B.V. All rights reserved