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BACKGROUND Pneumonia of uncertain cause has been reported in Wuhan, China since the beginning of early December 2019. In early January 2020, a novel strain of β-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients, which was recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is evidence of human-to-human transmission and familial cluster outbreak of SARS-CoV-2 infection. The World Health Organization(WHO) recently declared the SARS-CoV-2 epidemic a global health emergency. As of February 17, 2020, 71329 laboratory-confirmed cases (in 25 countries, including the United States and Germany) have been reported globally. Other than its rapid transmission, the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) remain unclear. In December 2019, coronavirus disease (named COVID-19 by the WHO) associated with the SARS-CoV-2 emerged in Wuhan, China and spread quickly across the country. AIM To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province, a Chinese region about 1800 km north of Wuhan. METHODS The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed. The cases originated from eight cities in Liaoning province. RESULTS The median age of the patients was 45 years, and 57.1% of them were male. No patient had been in direct contact with wild animals. Among them, 23 patients (41.1%) had resided in or traveled to Wuhan, 27 cases (48.2%) had been in contact with confirmed COVID-19 patients, 5 cases (8.9%) had been in contact with confirmed patients with a contact history to COVID-19 patients, and 1 case (1.8%) had no apparent history of exposure. Fever (75.0%) and cough (60.7%) were the most common symptoms. The typical manifestations in lung computed tomography (CT) included ground-glass opacity and patchy shadows, with 67.8% of them being bilateral. Among the patients in the cohort, 78.6% showed reduction in their lymphocyte counts, 57.1% showed increases in their C-reactive protein levels, and 50.0% showed decreases in their blood albumin levels. Eleven patients (19.6%) were admitted to intensive care unit, 2 patients (3.5%) progressed to acute respiratory distress syndrome, 4 patients (7.1%) were equipped with non-invasive mechanical ventilation, and 1 patient (1.8) received extracorporeal membrane oxygenation support. There were 5 mild cases (5/56, 8.9%), 40 moderate cases (40/56, 71.4%), 10 severe cases (10/56, 17.9%), and 1 critical case (1/56, 1.8%). No deaths were reported. CONCLUSION SARS-CoV-2 can be transmitted among humans. Most COVID-19 patients show symptoms of fever, cough, lymphocyte reduction, and typical lung CT manifestations. Most are moderate cases. The seriousness of the disease (as indicated by blood oxygen saturation, respiratory rate, oxygenation index, blood lymphocyte count, and lesions shown in lung CT) is related to history of living in or traveling to Wuhan, underlying diseases, admittance to intensive care unit, and mechanical ventilation.

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

This article reports two asymptomatic cases of SARS-CoV-2 infection. Both cases came from Hubei Province. One was a 63-year-old male and the other was a 29-year-old female. Both were diagnosed with SARS-CoV-2 infection during the screening of high-risk personnel from the affected areas. During the 14-day isolation medical observation, they had no symptoms, their blood lymphocyte count and lung CT examinations were normal. An asymptomatic infection had been diagnosed, however, it was not “asymptomatic infection” state in incubation period. Due to the timely and effective isolation measures taken for the two cases, no other persons have been infected by them. Therefore, effective control of the source of infection, cutting off the route of transmission, and protecting vulnerable populations are currently effective measures to prevent the spread of coronavirus infected disease.

Background:. Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. Methods:. From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. Results:. After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P

Background. Diabetic cognitive impairment (DCI), a serious complication of diabetes mellitus (DM), is gaining more acceptance and attention. The learning and memory function of diabetics always decreases. Traditional Chinese medicine (TCM) has been demonstrated to be effective in treating the symptoms in China, and thereinto Chinese medicinal herbs (CMH) are the most widely used. The objective of the present study was to review and analyze the existing data about reducing the symptoms in CMH treatment for DCI. Methods. Electronic literature databases (PubMed, EMBASE, CNKI, SinoMed, and Wan fang) were searched for randomized controlled trials conducted in China, comparing CMH with western medicines in the treatment of DCI, up to April 1, 2018. We applied standard meta-analytic techniques to analyze data from papers that reached acceptable criteria. Result. Nine randomized controlled trials (n = 576) on CMH were included. We found moderate evidence that CMH used alone or in combination with western medicines was more effective than western medicines alone in reliving the symptoms for DCI (total effective rate, odds radio (OR) = 4.64 (2.60, 8.29), and 95% confidence interval, P Conclusions. These findings demonstrated that CMH used alone or in combination with western medicines were apparently better than western medicines alone in the treatment of DCI. Because of the poor quality of the studies that were available for the present meta-analysis, further researches are still needed to support these early findings.

Background: B-acute lymphoblastic leukemia (B-ALL) with t(v;11q23)/MLL-rearrangement (MLL-r) in children (1 year or older) is rare, and its outcome and optimal treatment options remain controversial. This study aimed to analyze the clinical characteristics and outcomes of these patients, and to explore the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially haploidentical HSCT (haplo-HSCT) in the treatment of these patients. Methods: At the time of the last follow-up (July 1, 2019), we retrospectively analyzed clinical data of 42 non-infant children with t(v;11q23)/MLL-r B-ALL. Comparison of outcomes was made between patients received allo-HSCT in the first complete remission (CR1) and chemotherapy only. Results: The median follow-up was 41 (1-106) months. The median age at diagnosis was 4.5(1-14) years and the median leukocyte count was 56.0 (2.2-735.2)×109/L. One was excluded for death during induction. For the remaining 41 patients, the complete remission rate after induction therapy was 40/41 (97.6%), the estimated 4-year probabilities of overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 59.7%, 51.6% and 43.4%, respectively. 19 patients received allo-HSCT in CR1 (HSCT in CR1 cohort), notably, 18/19 cases in this cohort received haplo-HSCT, and the remaining 22 patients continued the consolidation therapy (Non-HSCT in CR1 cohort). The estimated 4-year probabilities of OS, EFS and CIR in the HSCT in CR1 cohort were 86.6%, 89.2% and 5.3%, respectively. Meanwhile, the estimated 4-year probabilities of OS, EFS and CIR in the Non-HSCT in CR1 cohort were 37.5%, 19.9% and 75.6%, respectively. They were considered to be statistically significant. Of the 17 patients who relapsed during consolidation chemotherapy, 9 patients who underwent chemotherapy only (Non-HSCT after relapse cohort) all died within 44 months. For the remaining 8 patients who chose allo-HSCT (HSCT in CR2 cohort) when they achieved the second complete remission (CR2), the estimated 4-year probability of OS was 47.6% (P=0.002). Multivariate analysis showed that HSCT in CR1 was the only independent protective factor for OS, EFS and CIR, and age at diagnosis (≥10 years) was an independent risk factor of OS. Conclusions: Allo-HSCT (especially haplo-HSCT) in CR1 may reduce the risk of relapse and improve prognosis in non-infant children with MLL-r B-ALL. In addition, allo-HSCT also seemed to be an effective approach to improve the prognosis of relapsed patients. Thus, haplo-HSCT could be an alternative approach for non-infant children with MLL-r B-ALL. Disclosures No relevant conflicts of interest to declare.

AIM To detect the expression of type I inositol 1,4,5-trisphosphate receptor (IP3RI) in the kidney of rats with hepatorenal syndrome (HRS). METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine (D-GalN) plus lipopolysaccharide (LPS; group G/L, n = 50), D-GalN alone (group G, n = 25), LPS alone (group L, n = 25), and normal saline (group NS, n = 25), respectively. At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylin-eosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3RI protein and mRNA in the kidney, respectively. RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3RI protein expression began to rise at 3 h (P < 0.05) and peaked at 12 h (P < 0.01). Real-time PCR demonstrated that IP3RI mRNA expression began to rise at 3 h (P < 0.05) and peaked at 9 h (P < 0.01). CONCLUSION IP3RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.

Hepatoid adenocarcinoma of the lung (HAL) is a rare type of lung cancer. Its diagnosis and treatment may be difficult due to the varied presentation; however, immunohistochemical analysis facilitates the diagnosis. The present study presents a case of HAL. The patient was a 48-year-old male who presented with a primary complaint of back pain. A chest computed-tomography scan revealed a lobulated soft-tissue mass that extended from the left lung apex to the middle and posterior mediastinum. The area of the largest cross-section was 7.9×10.0 cm and the lymph nodes did not demonstrate metastasis. Immunohistochemical staining of a transbronchial lung biopsy revealed that the tumor cells were α-fetoprotein (AFP)(positive) and hepatocytes(positive) and a diagnosis of hepatoid carcinoma of the left lung was established. The level of serum AFP, a tumor marker, was elevated (6,283 ng/ml). The patient presented with mediastinal metastases and was classified as stage IIIA (N2); following diagnosis, the patient received concurrent chemoradiation. Subsequent to chemoradiation, the left lung lump with the largest cross-section was 3.3×4.2 cm and the serum AFP had fallen to its lowest level (23.11 ng/ml). However, when the patient relapsed, the serum AFP level elevated markedly (57,800 ng/ml). Furthermore, the nodules of metastasis increased in number and enlarged, with the largest measuring 2.1 cm. The patient succumbed as a result of a lung infection.

OBJECTIVE: To evaluate comprehensively the association of cytotoxic T-lymphocyte antigen 4 (CTLA-4) +49A/G polymorphism with susceptibility to primary biliary cirrhosis (PBC). METHODS: PubMed was used to search for the relevant published articles. The risk of PBC association with the CTLA-4+49A/G polymorphism was estimated for each study in a random-effects model. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each study. Risks to PBC were estimated by stratified analysis in patients with different ethnicity and antimitochondrial antibody (AMA) status, as well as histological stages. RESULTS: A total of 12 articles were included in the study. An association between PBC and CTLA-4 G allele was found, overall OR = 1.20, 95% CI 1.03–1.41 (P = 0.02). However, stratification by ethnicity indicated a significant association between the G allele and PBC in Asians (OR = 1.36, 95% CI 1.12–1.65, P = 0.002), but not in Caucasians (OR = 1.15, 95% CI 0.95–1.39, P = 0.15). Moreover, AMA positive patients carrying G allele were more susceptible to PBC compared with AMA negative patients (OR = 1.23, 95% CI 1.06–1.43, P = 0.007; OR = 0.98, 95% CI 0.71–1.34, P = 0.88, respectively). CONCLUSIONS: Polymorphism in exon 1 of CTLA-4 gene at position 49 may act as a candidate of susceptibility locus to PBC. However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.

• Potentially inappropriate medication (PIM) use is a major patient safety concern for the elderly. • Using explicit criteria, previous studies found that 23.5% and 21.3% of the U.S. communitydwelling elderly used at least one PIM in 1987 and 1996, respectively.1 • The Beers criteria, Zhan criteria, and Health Plan Employer Data and Information Set (HEDIS) quality measure have been widely used for evaluation of health care quality and medication safety in older population.1-6

Background and Aims: Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B (CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to explore potential predictive factors. Methods: Sixty one HBeAg-negative CHB patients who had received lamivudine for at least 24 months and had maintained undetectable serum hepatitis B virus (HBV) DNA plus normal alanine aminotransferase for ≥ 18 months before withdrawal were included. They were followed up monthly during the first 4 months and at 3-month or 6-month intervals thereafter. Relapse was defined as serum HBV DNA ≥ 104 copies/mL. Results: Thirty one of 61 patients relapsed during follow-up, over 90% occurred within 18 months after lamivudine withdrawal. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 26.2%, 43.6%, 49.7%, 52.1%, 56.1% and 56.1%, respectively. Cox regression revealed that age was the only predictive factor for relapse, with lower relapse rates found in younger patients. Hepatitis B surface antigen (HBsAg) turned negative in eight patients, and none of them relapsed during follow-up. Conclusion: Effectiveness of lamivudine treatment is not durable in HBeAg-negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged ≤ 20 years. The ideal end point of lamivudine treatment is clearance of serum HBsAg.

The peripheral neutrophils are one of the main inflammatory cells and significantly influence the damage of endothelium. Type 2 diabetes is a manifestation of an ongoing low-grade inflammation. In diabetes, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation were detected, which associated closely with adhesion molecules expressed on neutrophils and endothelial cells. To detect the expression of syndecan-1 on neutrophils in patients with type 2 diabetes mellitus, we recruited 29 patients with type 2 diabetes mellitus without any diabetic complication and 24 healthy subjects (controls). Expression of syndecan-1 was determined by flow cytometry, and potential correlations between syndecan-1 and clinical characteristics were analyzed. On neutrophils, percentage of positive syndecan-1 cells was significantly higher in subjects with diabetes (10.363 ± 1.689%) than that of the controls (3.775 ± 0.634%, P = 0.001). An association between body mass index (BMI) and percentage of positive syndecan-1 neutrophils was detected (r = 0.415, P = 0.025). When BMI was categorized into subgroups of ≤25 kg/m2 (n = 10) and >25 kg/m2 (n = 19), the average percentages of positive syndecan-1 neutrophils in patients with diabetes were 5.733 ± 1.842% and 12.642 ± 2.251%, respectively (t = −2.137, P = 0.042). A multiple regression analysis showed that BMI (β = 0.783, P < 0.000) was a significant predictor of positive syndecan-1 neutrophils in subjects with type 2 diabetes.

To investigate whether rhegmatogenous retinal detachment (RRD) alters intraocular soluble syndecan-1 levels.In all, 39 samples of subretinal fluid (SRF) and 10 samples of vitreous fluid from RRD patients were collected. Using ELISA, soluble syndecan-1 levels were detected, and potential correlations between syndecan-1 levels with clinical parameters were analyzed.Soluble syndecan-1 in the vitreous fluid (2.577+/-0.578 ng/ml) and in the SRF (1.499+/-0.184 ng/ml) from eyes with RRD enhanced significantly compared to that of the controls (0.224+/-0.095 ng/ml) (p0.0001 and p=0.006). An increase in the syndecan-1 concentrations in SRF samples correlated with a longer duration of retinal detachment (r=0.716, p0.0001) and a younger age (r= -0.341, p=0.017).RRD was found to be associated with a significant increase of soluble syndecan-1 in the vitreous fluid and SRF. In SRF, an enhanced soluble syndecan-1 concentration correlated positively with the duration of retinal detachment and inversely with the age of patients.

To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome.Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide (LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration, and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker.Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed, especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase, 3389.5 ± 499.5 IU/L; blood urea nitrogen, 13.9 ± 1.3 mmol/L; Cr, 78.1 ± 2.9 μmol/L; K(+), 6.1 ± 0.5 mmol/L; Na(+), 130.9 ± 1.9 mmol/L; Cl(-), 90.2 ± 1.9 mmol/L; tumor necrosis factor-α, 1699.6 ± 599.1 pg/mL; endothelin-1, 95.9 ± 25.9 pg/mL; P0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/LPS, and was characterized by massive hepatocyte necrosis, while the structures of glomeruli, proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate (GFR)1, 0.79 ± 0.11 mL/min; GFR2, 3.58 ± 0.49 mL/min·kgBW(-1); GFR3, 0.39 ± 0.99 mL/min·gKW(-1)]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction.The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.

Background: CD19 chimeric antigen receptor (CAR)-modified T cell therapy has demonstrated clinical efficacy but often associated with severe adverse effects manifested by cytokine release syndrome (CRS). To increase safety and efficacy of CAR T therapy, a 4thgeneration CAR design has been developed and investigated in a multi-center trial in China. Patients and Methods: From July 2013 to July 2016, the 4SCAR19 phase I/II multi-center trial has enrolled 125 patients (pts) with chemo-resistant, CD19-positive, acute B cell lymphoblastic leukemia (B-ALL) eligible for CAR T cell preparation and infusion. Laboratory data and clinical records were carefully evaluated and 102 pts were qualified for statistical evaluation, including 55 children and 47 adults; 27 had received allo-HSCT prior to CAR T therapy. The median age is 9 (2 to 17) and 37 (19 to 70) for pediatric and adult pts, respectively. The median leukemia blast count in the bone marrow (BM) is 14.5%, with BM blast >50% accounting for nearly one third (33 pts). Autologous/donor T cells were apheresis collected and transduced with an apoptosis-inducible, safety-engineered lentivector CAR containing four intracellular signaling domains: CD19-scFv//CD28/CD137/CD27/CD3ζ-iCasp9 (4SCAR19). Pts received conditioning regimens of cyclophosphamide (17), cyclophosphamide/fludarabine (54), other chemotherapy (29) or none (2), followed by CAR-T cell infusion (average 1.05x106cells/kg). The quality of apheresis cells, gene transfer and T cell proliferation efficiencies, and effective CAR T infusion dose were quantitatively monitored. Statistical analysis used COX proportional hazard model involving categorical or continuous covariates, univariates, or multivariates analyses, and survival analysis was based on right-censored data and Kaplan-Meier estimation (KM curve). Results: The compiled data indicate that the quality of CAR T cells positively correlated with overall survival (OS). The median follow-up time was 7 months (range from 1~35 months). Patient (Pt) cohort 1 ( 5%) BM blasts, the CRS grade showed no significant correlation with disease burden (P = 0.45 for low burden group, and P = 0.06 for high burden group). Of note that total 73 of the 102 pts experienced 0-1 grade CRS and 8 of them had very high BM leukemia load (>80%), suggesting a very low toxicity of the 4SCAR19 T cells. In addition, of the 17 high (> 80%) BM blast pts, only 3 experienced grade 3-4 CRS. For 38 pts with BM blast ≥ 50%, most had grade 1 (30) or grade 2 (13) CRS, and only 5 pts had grade 3, and 3 pts had grade 4 CRS. For low burden pts (0-5% BM blasts), 86% (42 pts) developed low grade CRS (0 or 1), and even pts with BM blasts above 5%, 53% experienced low grade CRS (0 or 1). Further analysis of inflammatory genetic profile reveals that high CRS might correlate with high inflammatory profile, as several pts with high inflammatory gene patterns, while only had residual disease or no detectable leukemia cells (BM blasts 0-0.005%), developed grade 3-4 CRS. Conclusion: The three-year follow-up of the 4SCAR19 T cell therapy further supports that CAR T immunotherapy could benefit not only low leukemia burden pts, but also late-stage, chemo-resistant, very high-burden leukemia pts. Importantly, our study demonstrates a good safety profile of the 4SCAR19 T cells even under high disease burden. While the multicenter trial involves 22 clinical centers, the variable clinical settings do not seem to impact patient outcomes due to the highly standardized CAR T cell preparation protocol and manageable CRS in most. Disclosures No relevant conflicts of interest to declare.

The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF.

The objective of this paper was to study the therapeutic effect of Stigma maydis polysaccharides in diabetic mice. Mouse models of types 1 and 2 diabetes were established. The body weight, food intake, water intake as well as blood sugar level and glucose tolerance of mice were measured. Stigma maydis polysaccharides can improve the symptoms of weight loss and polydipsia in diabetic mice, and had an obvious antagonistic effect on alloxan-induced hyperglycaemia. The glucose tolerance test also showed that the Stigma maydis polysaccharides had very good effects on suppression and prevention of acute hyperglycaemia. Stigma maydis polysaccharides have some improvement effect on alloxan-induced types 1 and 2 diabetes.

Background: Relapsed/refractory leukaemia is associated with poor prognosis. T cells genetically modified to express CD19-specific chimeric antigen receptor (CD19CAR) in patients (pts) with chronic lymphoblastic leukemia (CLL) and acute lymphoblastic leukemia (ALL) have shown a remarkable ant-cancer activity. However, many questions remain related to the predictive indicators of long-term response and the management of cytokine release syndrome (CRS) after CAR-T cell infusion. In this phase II multi-center clinical trial, we evaluated the safety and efficacy of a fourth generation, safety-improved CD19-CAR (4SCAR19) in B-ALL pts. Patients and Methods: Fifty evaluable B-ALL patients (pts), with demonstrated persistent disease following salvage chemotherapy from 14 hospitals in China between July 2013 and June 2015 have been enrolled. The mean age is 14 (from 3 to 65) including 26 children and 24 adults. Leukemic genotypes include 16 Bcr-Abl (13 pT315I), 11 WT-1, 3 MLL-AF4, 3 E2A-PBX-1, 1 TEL/AML1, 1 IKZF1, 1 K-ras and the remaining 14 pts have undetectable genotype. Their disease characteristics include: 4 hypercritical acute leukemia, 10 extramedullary leukemia (7 CNSL, 3 multiple sites), with associated co-morbidity: 12 Aspergillus pneumonia, 4 cGVHD, 2 pleura/pericardial cavity effusion, 2 hepatitis B, 2 diabetes mellitus, 1 gastrointestinal hemorrhage, and 1 liver/spleen abscess. Twenty-one (42%) pts received allo-HSCT including 15 haplo-identical, 5 matched related donor (MRD) and 1 unrelated cord blood (URD-CB). These pts who relapsed after transplantation have received chemotherapy (chemo), combined with Tyrosine Kinase Inhibitors (TKIs, 10), donor leukocyte infusion (DLI, 19), or dendritic cells-cytokine induced killer cell (DC-CIK)/NK cell infusions (7). CAR-T cells were prepared from autologous (37), transplant donor (12) or non-transplant donor mother (1). T cells. Peripheral lymphocytes were collected from leukapheresis, and T cells were transduced with a 4th generation, safety-engineered, CD19scFv/CD28/CD137/CD27/CD3ζ-iCasp9 (4SCAR-19) lentivector. Pre-CAR-T lymphodepleting chemotherapy includes individualized chemo in 17 pts, and the others received Fludarabine (Flu) + Cyclophosphamide (Cy)(FC), or either Flu or Cy regimen: (1) FC: Cy 250mg/m2/d x3d and Flu 30mg/m2/d x3d ,or (2) either Flu x3 days, or (3) Cy x3 days, followed by CAR-T infusions at a dose of 2.13 (range from 0.42 - 5.9) x106 CAR-T cells per kg body weight per infusion. Results: For statistical analysis, 50 patients were divided into 2 cohorts: Cohort 1: B-ALL with morphological blast Toxicities: CRS occurred in most pts within the first 10 days of CAR-T cell infusion. 47/50 (94%) pts developed fever with elevated IL-2, IL-6, IL-10, and interferon gamma. Eight (16%) pts required either 12.5 mg Etanercept or 8 mg/kg tocilizumab, and three pts were treated with both drugs. Four pts developed hypotension and fully recovered after receiving dopamine. Four pts were treated once by methylprednisolone (1 mg/kg/day). The median follow-up was 4 months (range from 3~24 month), with 16 pts followed up for more than 6 months. Clinical outcomes: 1. LFS: The 120 days LFS for pts in cohort 1 and cohort 2 were 86% (CI,80%~93%) and 44.4% (CI, 31%~58%, P=0.0030), respectively. 2. OS (10 month) probabilities for patients in cohort 1 and cohort 2 were 82% (73%~91%) and 36% (19%~52%) (P= 0.0029), respectively. Conclusion: Our results indicate the potential of rapid leukemia eradication kinetics of 4SCAR19 therapy in treating chemo-resistant B-ALL. This therapy dramatically improves the prognosis of B-ALL pts by either providing a bridging approach to allo-HSCT or a better remission induction with longer period of CR than the routine treatment. Moreover, pts with morphological blasts Disclosures Dong: America Yuva Biotech: Consultancy, Other: clinical consultation.

Objective To retrospectively evaluate the effect of the third party umbilical cord blood on haplo-identical hematopoietic stem cell transplantation. Methods From June 2012 to May 2015, 125 leukemia patients were enrolled, including 41 cases of ALL, 62 cases of AML, 12 cases of MDS, 7 cases of CML-BP, 2 cases of acute mixed leukemia and 1 case of Mother cell dendritic cell tumor. Inclusion criteria: 1) AL patients; 2) halpo-identical HSCT; 3) 3/6 matched cord blood was available. Patients were divided into two groups, ie. group A (HSCT, n=65) and group B (HSCT plus umbilical cord blood transfusion group, n=60). Myeloablative conditioning regimens consisted of BuCy, TBI/FLAG, TBI/Cy, and FLAG that followed by reduced-intensified BUCY. The median dose of mononuclear cells in group A and B were 8.58×108/kg and 9.01×108/kg, respectively. The median dose of CD34+ cells for transfusion in each group were 3.67×106/kg and 2.94×106/kg, respectively. The dose of grafted UCB MNCs and CD34+ cells for group B were 3.5×107/kg and 2×105/kg, respectively. All patients received cyclosporineA, MMF and methotrexate for GVHD prophylaxis. The endpoints of this study were hematological engraftment, incidence of acute and chronic GVHD, incidence of relapse, transplant-related mortality(TRM), non-relapse mortality(NRM), Overall survival(OS) and Disease-free survival(DFS) in each group. Results The median follow-up time was 17(3-29) months in group A and 18(3-35) months in group B. Patients in group A reached a sustained ANC of more than 0.5*109/L at a median of 11 days, whereas 14 days in group B. Platelet more than 20*109/L occurred at a median of 19 days in group A, whereas 17 days in group B (P= .4). The rate of aGVHD was not significantly different in the two groups, 56.9% in group A and 48.3% in group B (P= .21). The accumulative incidence of II-IV grade aGVHD was 35.4% in group A and 30% in group B (P= .42). The incidence of chronic GVHD was 79.2% in group A and 71% in group B (P= .47). The incidence of extensive type was lower in group B, 69.2% Vs 35%, P=0.09. The incidence of CMV was lower in group B, 80% Vs 60% (P= .01). The accumulative incidence of EBV was lower in group B, 35.4% Vs 3.3% (P Disclosures No relevant conflicts of interest to declare.

Objective To retrospectively evaluate the results of allogeneic halpo-identical hematopoietic stem cell transplantation for high-risk leukemia. Methods From June 2012 to January 2015, total 60 patients with high-risk leukemia were enrolled, including 18 cases of ALL, 37cases of AML and 5 case of CML-BP. Including criterions: 1) ≥CR1; 2) relapse within 6 months after remisson. The average leukemia burden was 53% in bone marrow. All patients received HLA haplo-identical stem cells transplantation from parent or sibling donors. Myeloablative conditioning regimens consist of 7cases of BuCy, 26 cases of TBI/FLAG, 15 cases of TBI/Cy, and 12 cases of FLAG that followed by reduced-intensified BUCY. All patients received cyclosporine A, MMF and methotrexate for GVHD prophylaxis. Analyzed outcomes were hematological engraftment, incidence of acute and chronic GVHD, incidence of relapse, and nonrelapse mortality (NRM), Overall survival (OS) and Disease-free survival (DFS). Results The median mononuclear cells and CD34+ for transfusion were 9.08(7.02-24.4)*108/Kg and 3.42(0.8-12.1)*106/Kg. All 60 patients achieved stable engraftment. The median time of ANC≥0.5*10^9/L was 16 (8-23) days. And for platelet ≥20*10^9/L, the median was 22 (8-150) days. 38 patients developed acute GVHD, the accumulative incidence of aGVHD was 66.4%, the accumulative incidence of II-IV grade aGVHD was 35%, and the accumulative incidence of III-IV grade aGVHD was 15%. 26 patients developed cGVHD (12 patients extensive, 14 patients limited), the accumulative incidence of cGVHD was 88.2% and for extensive type, the accumulative incidence was 67.4%. The accumulative incidence of CMV infection was 54.1%, and the accumulative incidence of EBV infection was 16.3%. 10 patients developed virus cystitis. The number of Bacterial and fungal infected patients were 51 and 27, respectively. The median follow-up time post transplantation was 11(1-36) months, 14 patients relapsed and the accumulative incidence of relapse was 27%. For AML, ALL and CML-BP patients, the accumulative incidence of relapse were 26.6%, 34.8% and 0%, respectively. The median follow-up time post transplantation was 11months, 21 patients died and the main causes were relapse (11 cases), infection (5 cases), cGVHD (2 cases) and diffuse alveolar hemorrhage (3 cases). Among 60 patients, 39 patients survived. The one-year and two-year accumulative incidences of OS were 61.8% and 49.5%, respectively. The one-year and two-year accumulative incidences of DFS were 53.8% and 47.8%, respectively. For AML, ALL and CML-BP patients, the two-year accumulative incidence were 52.6%, 34.4% and 66.7%, respectively. The non-relapse mortality was 10. The one-year and two-year accumulative incidences of NRM were 19.4% and 28.4%, respectively. Conclusion Our clinical results have shown that the salvaged HSCT is a promising modality for treatment of high-risk AL with high leukemia burden. Disclosures No relevant conflicts of interest to declare.

Haploidentical hematopoietic cell transplantation (HCT) has been used to treat hematologic malignancies, but it is unknown whether the procedure is more effective in adults or children. To address this question, we analyzed patients aged 1 to 65 years old receiving myeloablative conditioning regimens followed by family 2 to 3 antigen HLA-mismatched HCT and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR; n = 137) or performed in Dao-Pei Hospital in China, China (n = 181). The Dao-Pei cohort had more acute and chronic graft-versus-host disease (GVHD), less relapse, lower transplant-related mortality (TRM), and better leukemia-free survival (LFS) than the CIBMTR cohort. Overall survival (OS) and outcomes were similar between adults and children. In the CIBMTR cohort receiving ex vivo T cell depletion (TCD), adults had higher TRM (relative risk [RR] 2.71, 95% confidence interval [CI] 1.29-5.69, P = .008) and lower OS (RR 1.75, 95% CI 1.08-2.84, P = .023) than children. In the CIBMTR subset that did not receive ex vivo TCD, relapse was lower in adults compared to children (RR 0.24, 95% CI 0.07-0.80, P = .020), but TRM, LFS, and OS were similar. We conclude that outcomes in adults and children are similar overall, although children have better survival than adults if ex vivo TCD is used.

Heparan sulfate proteoglycans (HSPGs) are involved in the regulation of cell growth, apoptosis and lipid metabolism in vitro. Syndecans are the primary form of HSPGs. Syndecan-1 is involved in the processes of cell growth, differentiation, adhesion, wound healing and inflammation. Additionally, as a sinusoidal transmembrane HSPG facing the plasma compartment, syndecan-1 is a promising target to be involved in lipoprotein physiology. We aimed to examine the possible correlation of syndecan-1 and lipid profile in type 2 diabetes mellitus. In this study, serum syndecan-1 was detected by ELISA, and potential correlations between syndecan-1 and triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein a, apolipoprotein (apo) B, apoA1 and apoB/apoA1 were analyzed. Forty-one patients with type 2 diabetes and 31 age-matched, non-diabetic healthy subjects (controls) were enrolled. Syndecan-1 in patients with diabetes (26.15 ± 2.42 ng/ml) was significantly higher than that of the controls (16.85 ± 1.98 ng/ml, t = −2.98, P = 0.005). Serum syndecan-1 level correlated negatively with apoA1 (r = −0.46, P = 0.003). Multiple regression analysis showed that apoA1 (b = −0.43, P = 0.003) was a predictor of serum syndecan-1 levels in subjects with type 2 diabetes.

Abstract 228 Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an important alternative option for patients with hematological malignancies who need urgent transplant but without HLA matched either sibling or unrelated donor (Dao-Pei Lu et al., Blood 2006; 107:3065). Each patient usually has several haploidentical family members who could be selected as a donor. To determine the principal of donor selection among all available related haploidentical candidates, the clinical outcomes of a large series of haplo-HSCT in our hospital are analyzed. From April 2002 to April 2010, consecutive 440 patients with hematological malignancies who underwent haplo-HSCT were included. The median age of patients was 23 (3-59) years old. The diagnosis included AML (39.8%), ALL (35.9%), MDS (3.6%), CML (16.1%), and others (4.6%). Transplants at CR1 or CML-CP1, ≥CR2 or CML-CP2/AP, and advanced disease (refractory/relapsed acute leukemia or CML-BC) were 33.4%, 40.9% and 25.7%. HLA mismatched at 1, 2, 3 loci was 13.2 %, 27.5%, 59.3%, respectively. Transplants in sex-matched donor-recipient pair, female donor to male recipient, and male donor to female recipient were 55.1%, 33.0% and 13.9%. Major clinical characteristics among these three arms were similar. All patients received unmanipulated combined marrow and peripheral blood stem cells for transplant after BUCy2/CyTBI plus ATG conditioning. Fludarabine was substituted for cyclophosphamide in some patients due to impaired organ function. Prophylaxis and treatment of GVHD were reported previously. Steady hematopoietic reconstitution was seen in 98.6% of recipients. The cumulative incidences of grade II to IV acute GVHD and chronic GVHD were 32.6%, 61.3%, respectively. 100-day mortality was 10.5%. With the median follow-up of 32 (3-99) months, 2-year and 5-year overall survival (OS) rates for patients who were in different disease status were 57.9% and 52.9%. Univariate and multivariate analysis all showed that disease status before transplant, CD34+ cell dosage infused and sex-matched or not between donor and recipient but not HLA disparity and age were pivotal impact factors on survival. Two-year OS of transplants in sex-matched donor-recipient pair, female donor to male recipient, male donor to female recipient were 65.5%, 55.3%, 37.6, respectively (p=0.000). No significant differences were found on OS of transplants among haploidentical donors from sibling or parent or offspring or other relatives. In conclusion, our clinical results from a large series of transplants demonstrate that haplo-HSCT in sex-matched donor-recipient pair has survival advantage. Therefore, in haplo-HSCT, sex-matched donor should be the first choice, if not available, then female donor to male recipient could be the second option. Disclosures: No relevant conflicts of interest to declare.

Abstract 4095 Poster Board III-1030 The clinical outcomes of refractory/recurrent leukemia that salvaged by allogeneic hematopoietic cell transplantation (HCT) is usually poor. It is crucial for the management of those high-risk patients with appropriate conditioning regimens that balance the efficacy and safety well and with enhanced anti-leukemia effect post-HCT. Our previous study has shown that donor's dendritic cell-primed cytokine-induced killer cells (DC-CIK) is a safe and effective therapy in the management of early leukemia recurrence after allogeneic HCT, which fail to or ineligible for current standard treatment. Objective In present clinical study, we examine the efficacy of refractory/recurrent myelogenous leukemia salvaged by allogeneic HCT and prophylactic immunotherapy. Methods From September 2006 to May 2008, 30 patients with refractory/recurrent myelogenous leukemia (AML 29, CML-BC 1) were enrolled. The median age was 32 (12 to 55) years old. The median blasts in bone marrow were 36% (20% to 87%) prior to conditioning. The grafts were from HLA identical siblings (5), unrelated donors (7), and haploidentical family members (18). Conditioning regiments were individualized according to patients' status as following. Generally, the regimen with high-dose cytarabine plus BUCY2 was used (13 cases). The patients with impaired organ function received above regimen except with fludarabine instead of cyclophosphamide (11 cases). For the recipients with > 40% blasts in bone marrow, melphalan (2 cases) or aclarubicin (1 case) was added into the regimen or FLAG followed by reduced-intensified BUCY2 (3 cases) was employed in order to reduce leukemia burden. Cyclosporine A, methotrexate and mycophenolate mofetil were administrated for GVHD prophylaxis. To prevent leukemia relapse, immunosuppressants were tapered off early post-HCT. Prophylactic immunotherapy including cellular (DLI, DC-CIK, NK cells), and humoral (IL-2, IFN-a, thymosin) was used selectively in the patients who had no GVHD 120 days after HCT. Results The median mononuclear cells in the graft were 7.36 (3.49 to 11.5) ×108/kg. The median CD34+ cells were 4.06 (1.57 to 11.4) ×106/kg. The median CD3+ cells were 1.42 (0.75 to 3.61) ×108/kg. Twenty-nine patients attained sustained engraftment. One died of multi-organ failure before hematopoietic reconstitution. The median time for white blood cells > 1.0 × 109/L, and platelets > 20 × 109/L was 14 (10 to 21) days, 15 (12 to 26) days, respectively. Thirteen patients developed acute GVHD (grade I in 5, grade II in 7, and grade III in 1). Thirteen patients developed chronic GVHD after immunosuppressants' reduction or withdrawal. In addition, 13 patients received prophylactic immunotherapy due to lack of chronic GVHD 120 days post-HCT, then 7 of 13 developed chronic GVHD. With the median follow-up of 15 (3 to 35) months, two (6.7%) patients with AML had hematological recurrence. One patient attained durable complete remission again after treatment with chemotherapy followed by immunotherapy with DLI, DC-CIK, and NK cells. Five (16.7%) patients died (infections in 2, hematological relapse in 1, chronic GVHD in 1, and multi-organ failure in 1). 25 of 30 (83.3%) patients have been in continuous complete remission since salvaged HCT. Conclusion Our preliminary clinical results have shown that the combination of salvaged allogeneic HCT and prophylactic immunotherapy is a promising modality for the treatment of myelogenous leukemia in refractory/recurrent status, even with high leukemia burden. Disclosures: No relevant conflicts of interest to declare.

More alternative donor stem cell transplantation (SCT) has been performed in recent years in China due to lack of HLA identical siblings. Higher risk for developing acute graft-versus-host disease (aGVHD) has been seen in patients who receive haploidentical stem cell transplantation (haplo-SCT) compared with identical sibling SCT patients (Lu DP et al, Blood2006; 107: 3065). In a murine model, we have first demonstrated that the animals transplanted with three mixed bone marrow (A+B+C to A) were survived longer due to milder aGVHD compared with the mice transplanted with single allogeneic bone marrow (B to A). In current clinical trial, we examine whether cord blood (CB) as the third party cells could reduce aGVHD in haplo-SCT setting under the same principle investigator in two hospitals. Between January 2006 and April 2008, total 133 haplo-SCT patients with hematological malignancies were enrolled. The patients with advanced diseases were excluded. All patients received unmanipulated blood and marrow transplant after BUCy2 or CyTBI plus antithymocyte globulin (ATG, Genzyme 10mg/kg) as preconditioning. Cyclosporine, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Fifty-six patients received one unit of HLA 3–6/6 matched CB one day before SCT as CB group, and 77 cases did not receive CB as control group. The main clinical characteristics in both groups are comparable. All patients in both groups achieved full donor chimerism. Low levels of CB chimerism were detected in a few patients at early stage after SCT. No long-term CB engraftment was found. The cumulative incidences of grade II to IV aGVHD were 16.4% versus 38.4% (p=0.008) in CB group, control group respectively. The cumulative incidences of grades III to IV aGVHD for CB group versus control group were 9.2% versus 22.4% with p=0.043. The incidences of 100-day treatment-related mortality were 1.8% versus 10.4% (p=0.053) for CB group, control group respectively. Our preliminary clinical study has shown that CB as the third party cells could significantly reduce the incidences of aGVHD, especially for severe aGVHD, and also treatment-related mortality in haplo-SCT. The mechanism of this strategy need to be further investigated.

Invasive aspergillosis has high mortality in patients with hematological malignancies after chemotherapy or allogeneic stem cell transplantation (SCT) due to usually low response rate to current antifungal agents and relatively poor tolerance to the toxicities of the antifungal medicines. In this pilot clinical study, we explore to manage the patients with refractory invasive aspergillosis with aspergillus-specific cytotoxic T lymphocytes (aspergillus CTL). Ten patients who were either no longer response to antifungal medicines or have to stop antifungal agents due to severe toxicities were included in this clinical study. Diagnosis are ALL (2 cases), AML (5 cases), and CML (3 cases). The median age was 37 (10 to 62) years old. Seven of them received allogeneic SCT (unrelated 3 cases, haploidentical 3 cases, identical sibling 1 case), and 3 patients were after chemotherapy. Aspergillus CTLs were either donor origin (5 cases) or patient origin (5 cases) if original donor was not available. Patients received 1 to 3 infusions of aspergillus CTLs. The median CTLs infused were 3.61 (0.28–40.00) x 105/kg. No infusion-related reactions were noted. No pre-existed graft-versus-host disease deteriorated. With aspergillus CTL therapy, one of them (10%) achieved complete response, 6 patients (60%) improved significantly, 1 case was stable, and 2 patients became worse. Our preliminary data has shown that aspergillus-specific cytotoxic T lymphocyte is a safe and promising mean to manage refractory invasive aspergillosis in patients with hematological malignancies.

Leukemia relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is one of the main obstacles for survival. Immunosuppressant withdraw, chemotherapy, and donor lymphocyte infusion(DLI) are usually employed for management of recurrence after HSCT, but some patients have poor response to above therapy or have contraindications for DLI due to relapse at early stage after transplant or with active graft-versus-host disease (GVHD). Dendritic cell-primed cytokine-induced killer cells (DC-CIK) have been successfully applied in treatment of minimal residual disease (MRD) in our center for 12 years. In present pilot clinical study, we explore to manage early leukemia relapse after HSCT with donor’s DC-CIK in appropriate patients. The patients who relapsed in hematological (5–20% blasts in BM) or molecular or immunological (MRD>0.1% by flow cytometry) with at least one of the following criteria were included in this clinical trial. 1. No response to DLI; 2. Relapsed within 60 days after HSCT; 3. Relapsed with active GVHD. Total 18 patients (male 9, female 9) with median age 26 (4 to 42) years were eligible to this clinical study. The diagnosis included acute myeloid leukemia (AML 13), acute lymphoblastic leukemia (ALL 4) and chronic myeloid leukemia (CML 1) who failed to reach molecular remission with imatinib before transplant. The types of donor were HLA identical sibling (11), haploidentical family member (5), and unrelated donor (2). Six of 18 patients had either molecular or immunological recurrence, while 12 of 18 cases relapsed hematologically. The median cell dosage of DC-CIK infused was 2.34×109 (0.2–44×109). With DC-CIK treatment, overall 11 of 18 (61.1%) patients achieved complete remission (CR, molecular or immunological or hematological based on the disease status before DC-CIK). Among 6 cases in molecular or immunological recurrence, five of them (83.3%) obtained CR, while 12 patients with early hematological relapse, 6 of them (50%) returned to CR. Seven of 13 patients with AML, and all 4 cases with ALL responded to DC-CIK treatment, while a patient with CML had no therapeutic benefit from it. Among 7 cases without response to DC-CIK, one patient with CML achieved molecular remission with high-dose Imatinib, 1 case obtained CR after DLI later on, 1 patient survived with primary disease so far, and the remaining 4 patients died from leukemia recurrence. In 11 cases who responded to DC-CIK, 10 of them survived with median 359(164 to 1233) days. One patient died from transplant-related complications. Four patients developed GVHD after DC-CIK infusion and controlled completely with Cyclosporin A and Methylprednisolone. Our encouraging results indicate that Donor’s DC-CIK is a safe and effective therapeutic option in management of early leukemia recurrence after allogeneic HSCT, especially for the patients who fail to or ineligible to current standard practice.

Summary Background High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. Methods This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 109 platelets per L or a platelet count of less than 50 × 109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov , NCT04217148 , and is now completed. Findings Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516–6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. Interpretation The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. Funding The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.