Key Points• HLA-identical sibling transplantation for SCD offers excellent long-term survival. • Mortality risk is higher for older patients; event-free survival has improved in patients transplanted after 2006.Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n 5 873; 87%); the remainder received reduced-intensity conditioning regimens (n 5 125; 13%). Bone marrow was the predominant stem cell source (n 5 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Eventfree survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P < .001) and higher for transplantations performed after

High-dose immunosuppression and AHST were performed with acceptable toxicity in a small number of patients with newly diagnosed type 1 DM. With AHST, beta cell function was increased in all but 1 patient and induced prolonged insulin independence in the majority of the patients.

CCUMULATED CLINICAL EXPErience indicates that there is an inverse association between beta-cell function and chronic complications of type 1 diabetes mellitus (DM)-the higher the Cpeptide levels (an indirect measure of viable beta-cell function), the lower the incidence of microvascular complications of type 1 DM. 1 Since the establishment of the autoimmune etiology of type 1 DM in the late 1970s, many clinical trials analyzing the effects of different types of immune interventions demonstrated that beta-cell preservation is an achievable target in different degrees. 2,3 Based on the theory of possible reconstitution of immune tolerance after "immunologic reset" with autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT), 4 in 2007, we reported a phase 1/2 trial evaluating the safety and metabolic effects of autologous nonmyeloablative HSCT in 15 patients with newly diagnosed type 1 DM. 5 The majority of pa-Author Affiliations are listed at the end of this article.

The utilization of concentrated solar energy as external heat source for methane steam reforming has been investigated. Molten salts at temperatures up to 550°C can be used as solar heat carrier and storage system, and hydrogen selective membranes can be used to drive reforming reaction at lower temperatures than conventional (<550°C), with hydrogen purification achieved thereby. The combination of new technologies such as membranes and membrane reactors, concentrating solar power (CSP) systems, and molten salt heat carriers, allows a partial decarbonation of the fossil fuel together with the possibility to carry solar energy in the current natural gas grid. Different plant configurations and operating conditions have been analyzed using a mathematical model and AspenPlus simulator. © 2008 American Institute of Chemical Engineers AIChE J, 2008

for the Multiple Sclerosis-Autologous Hematopoietic Stem Cell Transplantation (MS-AHSCT) Long-term Outcomes Study Group IMPORTANCE Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. OBJECTIVE To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.DESIGN, SETTING, AND PARTICIPANTS Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.EXPOSURES Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. MAIN OUTCOMES AND MEASURESThe primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. RESULTSValid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). CONCLUSIONS AND RELEVANCEIn this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results suppor...

Mitochondrial neurogastrointestinal encephalopathy (MNGIE), usually an autosomal-recessive inherited condition, causes gastrointestinal dysmotility, ophthalmoplegia, ptosis, leukoencephalopathy and neuropathy. The chromosome 22 disorder, due to mutations in the nuclear gene TYMP encoding thymidine phosphorylase (TP), leads to the accumulation of thymidine and deoxyuridine, with mitochondrial dysfunction. This report describes a patient with an MNGIE-like syndrome with a heterozygous TYMP mutation who showed marked, but transient improvement postallogeneic haematopoietic stem cell transplantation (HSCT). The patient, showing ptosis and ophthalmoplegia, was initially managed for myasthenia gravis. She developed gastrointestinal symptoms, dysarthria, dysphagia and weakness, and MNGIE was considered due to its low TP levels and improvement after platelet transfusions. She underwent HSCT, with dramatic improvement, but regressed 18 months later despite normal TP levels, platelet counts and full chimerism. MNGIE may encompass a spectrum of disorders. TP deficiency alone is unlikely to explain all clinical signs, and other factors, including the possible development of anti-TP antibodies, which may play a role in the pathophysiology.

No abstract

Summary. We have determined the prevalence of methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C in 71 children (< 15 years) with acute lymphoblastic leukaemia (ALL) and in 71 control subjects. Odds ratio (OR) for ALL linked to MTHFR C677T was 0´4 (95% CI 0´2±0´8); for heterozygotes it was 0´5 (95% CI 0´2±0´9) and for homozygotes it was 0´3 (95%CI 0´09± 0´8). MTHFR A1298C yielded an overall OR for ALL of 1´3 (95% CI: 0´7±2´6); for heterozygotes it was 1´3 (95% CI: 0´7±7´6) and for homozygotes it was 2´8 (95% CI 0´5± 15´6). In conclusion, MTHFR C677T was linked to a significant 2´4-fold decreased risk of developing childhood ALL, whereas MTHFR A1298C did not significantly affect the risk of ALL in our population.