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Abstract: Objectives: To explore the possible risk factors for the occurrence and mortality of thrombotic microangiopathy (TMA) with concomitant acute graft‐vs‐host disease (aGVHD) and to investigate outcomes and treatments of this disorder after allo‐HSCT. Methods: Fifty cases diagnosed with TMA with concomitant aGVHD and 150 controls were identified from a cohort composed of 3992 patients who underwent allo‐HSCT from 2008 to 2016. Results: Grade III‐IV aGVHD (P = .000), acute kidney injury (AKI) (P = .033), and hypertension (P = .028) were significant independent risk factors associated with the occurrence of TMA with concomitant aGVHD. A haptoglobin level below normal (P = .013), a maximum volume of diarrhea >2500 mL/d (P = .015), and bloody diarrhea (P = .049) were significant markers for death in both univariate and multivariate analyses. Patients diagnosed with TMA with concomitant aGVHD had a lower overall survival (OS), a higher non‐relapse mortality (NRM), but a lower risk of relapse. Conclusions: Thrombotic microangiopathy with concomitant aGVHD is a significant complication after allo‐HSCT, with a worse outcome, including significantly lower OS and higher NRM. There are specific risk factors associated with occurrence and mortality of this complication. [ABSTRACT FROM AUTHOR]

Objective To retrospectively identify characteristics and risk factors of viral encephalitis ( VE) in patients who underwent a haplo-identical hematopoietic stem cell transplant ( HSCT). Methods A nested case-control study was designed. Cases with VE and controls were identified from a cohort composed of 1274 patients who underwent a haplo-identical HSCT from 2012 to 2015. Results VE was identified in 30 patients (2.4%). The median time from HSCT to diagnosis was 144.5 days. The viruses detected included RSV-B (43.3%), BKV (23.3%), more than one virus (10%), cytomegalovirus ( CMV) (6.7%), RSV-A (6.7%), HSV (3.3%), HHV-6 (3.3%), and CVB3 (3.3%). Alterations of consciousness and seizures were the most frequently presented symptoms. Neuroimaging detected abnormalities in 19 (76%) patients. The cerebral spinal fluid cell count, protein, and glucose concentration were elevated in eight (26.7%), 18(60%), and nine (30%) patients, respectively. The treatment efficacy and prognoses varied considerably based on the different causative viruses. Multivariate analyses revealed that acute graft-versus-host disease (grade III- IV), CMV viremia, and engraftment syndrome were significantly and independently associated with VE. The cumulative mortality rate was significantly higher in patients suffering from VE than in the controls. Conclusion Characteristics, such as onset time, response to treatment, and outcome, varied based on the different causative viruses. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous study found that the novel anti-inflammatory cytokine IL-35 could suppress aGVHD in patients after allo-HSCT. In this study, we used C57BL/6 (B6, H-2b) mice as donors and (B6 × DBA/2) F1 (BDF1, H-2b × d) mice as recipients to create a model of aGVHD and explore the relationship between IL-35 and aGVHD. The mice receiving IL-35 survived longer than did the control mice. We observed that treatment with IL-35 and RAPA could reduce the incidence of aGVHD. Additionally, this treatment inhibited intestinal and thymic epithelial cell apoptosis and liver infiltration by the donor T-cells, thereby ameliorating the enteropathy and liver injury caused by aGVHD. We found that IL-35 and RAPA also markedly suppressed TNF-α and IL-17A expression and enhanced IFN-γ expression in the intestine and liver. We measured Tregs in spleen and found that IL-35 and RAPA treatment expanded the number of Tregs in spleen. We found that the phosphorylation of STAT1 and STAT4 were inhibited in mice with aGVHD. In contrast, STAT1 and STAT4 were phosphorylated when the mice were treated with IL-35. IL-35 may have therapeutic potential in the treatment of aGVHD after allo-HSCT. [ABSTRACT FROM AUTHOR]