BackgroundImmunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.ObjectiveThis analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.MethodsClinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.ResultsWe confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS.ConclusionsPatients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.
Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients o18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88 ± 1% and 81 ± 1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91 ± 1% and 83 ± 1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90-96% and an EFS of 83-93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.
Key Points In β-thalassemia major patients with severe iron burden, deferasirox was noninferior to deferoxamine for myocardial iron removal. The ejection fraction was stable during treatment for both deferasirox and deferoxamine.
Higher mortality and morbidity are well established in children with malignancies in whom intensive care admissions are required. A retrospective cohort study was conducted to assess the risk factors for children with cancer in the pediatric intensive care unit (PICU) for short-term outcome (survival vs. nonsurvival when leaving the PICU). The records of 36 children with a median age of 5 years (range: 0.5 to 21) between August 2004 and August 2007 were reviewed. Mortality rate was 55%, higher than the yearly overall PICU mortality rate of 12% (P<0.0001). The mean Pediatric Risk of Mortality Score (PRISM) III score among survivors was lower than that among nonsurvivors (9.4+/-5.7 vs. 16.4+/-5.3, P=0.001). Comparison of observed and predicted mortality derived from the PRISM III score showed that distribution of outcome was not different and the prediction model performed well (goodness of fit test: chi=3.64, df=6, P=0.725). The mortality rates were 66.6% and 33.3% in patients with high (>10 points) and low (< or =10 points) PRISM III score, respectively (P=0.05). Mortality rate was significantly related to presence and number of organ system dysfunction (P=0.031 and P=0.013, respectively), sepsis (P=0.05), mechanical ventilation (P=0.005), and positive inotropic support (P=0.003). By using multiple logistic regressions, the independent risk factor was PRISM III score at the time of admission to PICU (P=0.05). The PRISM III score performed well as a predictor of outcome. For decision to admit such patients to the PICU or to forgo life-sustaining therapies, other factors such as need for mechanical ventilation and positive inotropic support, presence and numbers of organ system dysfunction should be taken into consideration as well.
Key Points• The outcome of HSCT in this large SCN cohort is acceptable.• Given the TRM, a careful selection of HSCT candidates should be undertaken.Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day 190) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken. (Blood. 2015;126(16):1885-1892 Medscape Continuing
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