Key Points• There is a need to identify the best HLA haplotypemismatched related donor.• Use of young, male, NIMAmismatched donors results in the best survival after HLA haplotype-mismatched related donor transplants. Older sister donors were inferior to father donors with regard to NRM (HR 5 1.87; 95% CI 5 1.10-3.20; P 5 .02) and survival (HR 5 1.59; 95% CI 5 1.05-2.40; P 5 .03). Noninherited maternal antigen-mismatched sibling donors were associated with the lowest incidence of acute GVHD compared with parental donors and noninherited paternal antigen-mismatched sibling donors. Specific HLA disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA haplotypemismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms. (Blood. 2014; 124(6):843-850)

CARMA1 mediates T cell receptor (TCR)-induced NF-kappaB activation. However, how TCR links to CARMA1 in the signaling pathway is not clear. Here, we show that CARMA1 is inducibly phosphorylated after TCR-CD28 costimulation. This phosphorylation is likely induced by PKCtheta, since PKCtheta induces phosphorylation of CARMA1 in vitro and in vivo. Our results indicate that the PKCtheta-induced phosphorylation of CARMA1 likely occurs on Ser552 on the Linker region of CARMA1. Importantly, expression of CARMA1 mutant, in which Ser552 is mutated, fails to mediate TCR-induced NF-kappaB activation in CARMA1-deficient T cells. The functional defect of this CARMA1 mutant is likely due to the fact that this mutant cannot be phosphorylated at the critical residue, thereby failing to recruit the downstream signaling components into the immunological synapse. Together, our studies provide the first genetic evidence that the phosphorylation of CARMA1 plays a critical role in the TCR signaling pathway.

BACKGROUND: Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Recently, a new strategy was developed for HLA-mismatched/haploidentical transplantation from family donors without in vitro T cell depletion (TCD). METHODS: Over the past 9 years, 756 patients underwent haploidentical transplantation using a protocol developed by the authors, which combines granulocyte-colony stimulating factor-primed bone marrow (G-BM) and peripheral blood stem cells without in vitro TCD. The long-term outcome with this treatment modality was reported, and a risk-factor analysis was provided. RESULTS: Of these patients, 752 (99%) achieved sustained, full donor chimerism. The incidence of grades 2 through 4 acute graft-versus-host disease (GVHD) was 43%, and the 2-year cumulative incidence of total chronic GVHD was 53%. The 3-year cumulative incidence of nonrelapse mortality was 18%. The 2-year cumulative incidences of relapse were 15% and 26% in the standard-risk and high-risk groups, respectively. Of the 756 patients, 480 survived throughout the follow-up period of 1154 days (range: 335-3511 days) with the 3-year leukemia-free survival rates of 68% and 49% in the standard-risk and high-risk groups, respectively. Lower leukemia-free survival was associated with high-risk disease status (P ¼.001), chronic myelogenous leukemia disease type (P ¼.004), neutrophil engraftment beyond 13 days after transplant (P ¼.012), and the occurrence of grades 2 through 4 acute GVHD (P ¼.019). CONCLUSIONS: The results from the authors' 9-year experience showed that G-BM combined with peripheral blood stem cells from haploidentical donors, without in vitro TCD, is a reliable source of stem cells for transplantation by using the

Key Points• Risk stratification treatment of t(8;21) acute myeloid leukemia may decrease relapse and improve longterm survival.• Allo-HSCT benefited high-risk patients, but impaired the survival of low-risk patients.We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P 5 .001).Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P 5 .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR- OCH-12002406. (Blood. 2013;121(20):4056-4062)

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BPA was positively associated with generalized obesity, abdominal obesity, and insulin resistance in middle-aged and elderly Chinese adults.

Background: Tfh cells regulate B cell-mediated humoral immunity. Results: STAT5 regulated Blimp-1 expression, and STAT5 deficiency in CD4 ϩ T cells resulted in an increase of Tfh generation

Primary angle-closure glaucoma (PACG) is a common cause of blindness. Angle closure is a fundamental pathologic process in PAGC. With the development of imaging devices for the anterior segment of the eye, a better understanding of the pathogenesis of angle closure has been reached. Aside from pupillary block and plateau iris, multiple-mechanisms are more common contributors for closure of the angle such as choroidal thickness and uveal expansion, which may be responsible for the presenting features of PACG. Recent Genome Wide Association Studies identified several new PACG loci and genes, which may shed light on the molecular mechanisms of PACG. The current classification systems of PACG remain controversial. Focusing the anterior chamber angle is a principal management strategy for PACG. Treatments to open the angle or halt the angle closure process such as laser peripheral iridotomy and/or iridoplasty, as well as cataract extraction, are proving their effectiveness. PACG may be preventable in the early stages if future research can identify which kind of angles and/or persons are more likely to benefit from prophylactic treatment. New treatment strategies like adjusting the psychological status and balancing the sympathetic-parasympathetic nerve activity, and innovative medicines are needed to improve the prognosis of PACG. In this review, we intend to describe current understanding and unknown aspects of PACG, and to share the clinical experience and viewpoints of the authors.