Objective:To demonstrate the type of CEBPA gene mutations among patients with acute myeloid leukemia (AML), clinical characteristics, and prognostic effect on patient outcomes.Methods:Demographic data, clinical features, laboratory characteristics, and data about treatment and follow-up of 57 patients with CEBPA mutated AML diagnosed at Peking Union Medical College Hospital between April 2016 and November 2022 were collected and analyzed.Results:In total, 57 patients with CEBPA mutation accounted for 16.1% of all the 353 patients with AML, among which 28 patients had CEBPA-bZIPinf and 29 had CEBPA-other. Compared with the CEBPA-other group, the CEBPA-bZIPinf group was younger (54 vs 64 years, P=0.010), de novo AML was more common ( P=0.001), and the level of bone marrow blast was higher (68.0% vs 36.3%, P=0.001). Moreover, 24 patients from the CEBPA-bZIPinf group and 19 from the CEBPA-other group received chemotherapy. The one-course complete remission (CR) rate of the CEBPA-bZIPinf group was significantly higher than that of the CEBPA-other (87.5% vs 47.4%, P=0.010) and CEBPA-wt (87.5% vs 50.3%, P=0.002) groups. After a median follow-up of 11 months, the median OS of the CEBPA-bZIPinf group was significantly longer than that of the CEBPA-wt group (not reached vs 22.1 months, P=0.012) . Conclusion:CEBPA-bZIPinf mutated AML is a unique clinical entity, with a younger age of diagnosis, better response to chemotherapy, and better prognosis.

Objective:Early death (ED) characteristics and predictive factors analysis in patients with severe/very severe aplastic anemia (SAA/VSAA) treated with intensive immunosuppression therapy and establish an ED prediction model.Methods:The clinical data of 232 patients with SAA/VSAA treated with Antithymocyte immunoglobulin (ATG) at the Peking Union Medical College Hospital from August 2003 to August 2021 were collected. The characteristics and causes of ED within 90 days were analyzed retrospectively. Cox proportional hazards model was used to screen the ED risk factors and build a prediction model.Results:Only 19 patients (8.2% ) developed ED with a median time of 24 (3-85) days among the 232 patients with SAA/VSAA who received ATG treatment. The main cause of ED was infection (84.2% ) , followed by cerebral hemorrhage (10.5% ) . Multivariate analysis showed that VSAA ( HR=15.359, 95% CI 1.935-121.899, P=0.010) , fungal infection prevention by posaconazole ( HR=0.147, 95% CI 0.019-1.133, P=0.066) , lymphocyte count (LYM) ≤ 0.5×10 9/L ( HR=3.386, 95% CI 1.123-10.206, P=0.030) , and PLT ≤ 5×10 9/L ( HR=8.939, 95% CI 1.948-41.019, P=0.005) were ED’s independent influencing factors. To build a clinical prediction model, VSAA, fungal infection prevention by posaconazole, LYM ≤ 0.5×10 9/L, and PLT ≤ 5×10 9/L were scored with 3, -2, 1, and 2, respectively. The integral model AUC=89.324 (95% CI 80.859-97.789) . The ED risk in patients with a score ≥ 3 was 23.1 (95% CI 5.3-100.2) times that in patients with a score<3. Conclusion:ED caused by infection and cerebral hemorrhage is an important challenge for SAA/VSAA to be treated with ATG. VSAA, LYM ≤ 0.5×10 9/L, and PLT ≤ 5×10 9/L patients who did not use posaconazole to prevent fungal infection had a high ED risk.

Objective:To investigate the efficacy of using a pediatric-inspired regimen for adolescents and young adults (AYA) with Philadelphia chromosome-negative (Ph -) acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) at a single center in China. Methods:Clinical data of 71 consecutive newly diagnosed AYA patients with Ph - ALL/LBL on a pediatric-inspired regimen in Peking Union Medical College Hospital from January 2012 to November 2018 were retrospectively analyzed. Results:Median age at diagnosis was 20 years (range: 15-38) , and 46 patients (64.8%) were male. Forty-nine (69.0%) had B-ALL/LBL. Among 62 ALL patients, 22 (35.5%) were high-risk. Complete remission rate was 93.0%. At follow-up with a median time of 44 months, the estimated 5-year disease-free survival (DFS) and overall survival (OS) was 56.3% and 64.3%, respectively. There was no significant difference in 5-year OS between allogeneic hematopoietic stem cell transplantation group and the continuous chemotherapy group after completion of 4 courses of chemotherapy. The 5-year DFS and OS for the non-high-risk group was 63.1% and 73.7%, respectively, which were significantly higher than 32.0% and 44.4% for the high-risk group, respectively ( P<0.001) . Conclusions:The use of pediatric-inspired regimen for AYAs with Ph - ALL/LBL was feasible and effective.

Objective:To investigate epidemic status of avian influenza virus (AIV) in live poultry market (LPM) and evaluate its potential public health threat and develop control measures in Nanchang city.Methods:Forty-seven LPM in 10 counties/districts of Nanchang city were selected as surveillance sites by using cluster random sampling. Poultry swabs and environmental samples were obtained from LPM. Real time RT-PCR was used for AIV typing and subtyping. Excel 2016, SPSS 24.0 and Prism Version 7 (GraphPad) software were used for statistical analysis.Results:Total of 9 248 poultry swabs and environmental samples were collected. 1 525 specimens(16.49%) were positive for AIV. H7 and H9 were the dominant subtypes, and H9 positive rate was highest (17.44%). Sewage (21.46%) and throat swabs (20.46%) had higher positive rates than the other types of samples. Chicken and duck were dominant hosts for AIV, the corresponding positive rates were 22.80% and 13.95%. The positive rates of Honggutan district, Anyi county and Xinjian district were 25.52%, 24.31% and 22.35%, which were higher than that of the other counties/districts. Each county/district had its unique subtype composition of AIV.Conclusions:The coexistence of H7, H9 and other subtypes of AIV in LMP was identified in Nanchang city. Continuing active surveillance and comprehensive control measures should be taken to reduce the potential risk of human infection.

Objective To evaluate the safety and efficacy of lenalidomide plus rituximab in treatment of the patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Methods The clinical data of the patients with relapsed/refractory B-NHL after the varieties of treatment methods in Peking Union Medical College Hospital between January 2015 and December 2017 were retrospectively analyzed. All the patients were treated with R2 regimen: oral lenalidomide (25 mg/d for day 1-day 21) and rituximab (375 mg/m2 of intravenous infusion on day 1, 28-day of each cycle); the efficacy was evaluated after three cycles. After this induction phase, the patients achieving complete response (CR), partial response (PR), or stable disease (SD) were given R2 regimen until the end of 8 cycles. The major end point was overall response rate (ORR) defined as CR + PR. Secondary end point included 1-year progression free survival (PFS), 1-year overall survival (OS) and grade 3-4 adverse events. T cell and B cell subsets of 7 patients at baseline were measured, and T cell and B cell subsets of 13 patients with good efficacy were dynamically observed. Results A total of 49 patients who received 1-4 chemotherapy regimens were included. The ORR after the R2 treatment for 3 courses was 65% (32/49). Thirty-six patients (9 cases of CR, 22 cases of PR, 5 cases of SD) were enrolled in R2 maintenance treatment. The median follow-up time was 13 months, 1-year PFS rate was 61% and 1-year OS rate was 84% . The most common adverse event was bone marrow suppression, including grade 3-4 neutropenia (27% ), grade 3-4 thrombocytopenia (6% ) and grade 4 anemia (4% ), most of which could be controlled by prolonging interval cycles or reduced lenalidomide dosage. The decreased number of CD19+B cell after treatment could be seen in 13 patients who obtained good efficacy under the dynamic observation. Conclusion Lenalidomide plus rituximab is well tolerated and highly active in the treatment of relapsed/refractory B-NHL.

Objective: To Evaluate the efficacy and safety of posaconazole as primary prevention of invasive fungal disease (IFD) in patients with severe aplastic anemia (SAA) treated with anti-thymus/lymphocyte immunoglobulin (ATG/ALG) combined with cyclosporine intensive immunosuppressive therapy (IST). Methods: A retrospective analysis of clinical data of 58 SAA patients who received IST of anti-thymocyte immunoglobulin combining cyclosporine and antifungal prophylaxis during April 2013 to May 2017 in Peking Union Medical College Hospital was performed. The patients were divided into posaconazole prophylaxis group and the control group (itraconazole or fluconazole). The disease characteristics, IFD prevention effect and adverse drug reaction, curative effect and prognosis of the two groups were compared. Results: Posaconazole was used to prevent fungal infection in 20 patients. The other 38 patients were used as the control group. Retrospective analysis showed comparable characteristics (gender, age, disease severity, etiology, interval between the onset of disease to treatment, ATG/ALG type) of both groups. The incidence of IFD were 0 and 15.8% in posaconazole prophylaxis group and the control group, respectively (P=0.084). In the control group, there were 6 cases diagnosed as IFD. Of them, 2 were confirmed, 2 suspected and 2 not identified. Five of the 6 cases were pulmonary infection, 1 bloodstream infections. Of the 6 IFD cases, 5 were very severe aplastic anemia (VSAA). There was no obvious adverse reaction in posaconazole prophylaxis group. Conclusion Posaconazole is safe and effective for primary prevention of fungal infection of SAA patients receiving IST, especially for the VSAA.

Objective: To evaluate the response of oral melphalan plus high-dose dexamethasone (MDex) for patients with primary light chain amyloidosis (pAL). Methods: Clinical data, hematological and organ responses, and survival of 76 patients with pAL who had received MDex from January 2009 to July 2017 were retrospectively analyzed. Results: Of 76 patients (47 males and 29 females with the median age of 56 [range, 20-74] years old), 19.70% patients were defined as Mayo 2004 stage 3, involvement of more than or two organs was presented in 65 (85.53%) patients. Among 60 response evaluable patients, overall hematological response was 48.33% with complete response of 20.00% and very good partial response of 20.00%, respectively. The median time to the hematological response was 5 (range, 1-15) months. 36.67% patients achieved organ response. After the median follow up of 23(range, 1-113) months for surviving patients, median progression-free survival (PFS) and overall survival (OS) were 34 and 43 months, respectively. In a three months landmark analysis, the median rates of PFS and OS were 46 and 65 months, respectively. The median OS rates of patients with Mayo 2004 stage 3 and non Mayo 2004 stage 3 were 5 and 65 months (P=0.001), respectively. Conclusions MDex was an effective treatment for patients with early stage pAL, but was not suitable for those with severe cardiac involvement.

Influenza vaccination is the most effective means to prevent and control influenza epi-demics, and the universal influenza vaccine which can induce broad and long-term protective effect is still in its infancy. Up to date, several broad neutralizing antibodies that can antagonize a variety of influenza A vi-ruses have been identified, and the crystal structure of the antibody and HA complex reveals at least three highly conserved epitopes. Deep insights into the molecular mechanism of the interactions between neutrali-zing antibodies and virus antigen can elicit a new strategy not only for rational design of universal influenza vaccines, but also for the development of antibody-based therapeutics against influenza virus. In this paper, advances in research of universal neutralizing antibodies and vaccines for Influenza A virus are reviewed.

Objective: To evaluate the clinical characteristics and outcomes of very high risk patients with primary immunoglobulin light-chain amyloidosis (pAL) at a single center in China. Method: Clinical data, treatment and outcome of 205 pAL patients in Peking Union Medical College Hospital from January 2009 to February 2016 were retrospectively analyzed. A 'very high risk’ group includes patients with Mayo 2004 stage Ⅲb and Mayo 2012 stage 4. Results: Of 205 patients, 34 (16.6%) were defined as very high risk pAL patients. The median age at diagnosis was 57 (20-84) years, and 22 patients (64.7%) were male. All 34 patients were diagnosed with cardiac involvement, multi-organ involvement was observed in 15 patients (44.1%) , and 27 (81.8%) had New York Heart Association Class Ⅲ or Ⅳ. Median values of serum cTnI, NT-proBNP, and free light chains difference were 0.25 μg/L, 11 733 ng/L, and 403 mg/L, respectively. Eight (24.2%) had more than 10% plasma cell on the bone marrow aspirate. Sixteen (47.1%) patients received bortezomib based chemotherapy and overall hematologic response rate was 58.3%. Median overall survival (OS) was 4 months. The estimated OS at 3, 6, 12, and 24 months was 51.3%, 44.0%, 35.2%, and 29.6%, respectively. Fourteen (41.2%) patients died within 3 months after the diagnosis. The estimated 1-year survival rate for the patients who got hematologic response, without hematologic response, and palliative treatment was 90.9%, 11.1%, and 0, respectively (P<0.001) . Conclusion Patients with very high risk pAL had very poor prognosis and the early death rate remained high. Those patients who obtained hematologic remission would have significantly better outcomes.

Objective: To evaluate the clinical characteristics, MYD88^L265P mutation, CXCR4^WHIM mutation and prognosis in patients with Waldenström macroglobulinemia (WM). Methods: The clinical characteristics, International Prognostic Scoring System for symptomatic WM (WPSS) , and overall survival (OS) were retrospectively assayed in 93 patients with newly diagnosed WM at Peking Union Medical College Hospital during January 2000 to August 2016. The MYD88^L265P mutation and CXCR4^WHIM mutation were tested among 34 patients. Results: The median age of the 93 patients was 64 years (range, 33-85 years) with a male-to-female ratio of 2.44. According to WPSS, we included 16 (17.2%) low-risk, 44 (47.3%) intermediate-risk and 33 (35.5%) high-risk patients. Eight patients had secondary amyloidosis. With a median follow-up of 44 (1-201) months, the median OS was 84 months. Cox regression multifactor analysis showed WPSS risk group (HR=2.342, 95% CI 1.111-4.950, P=0.025) , whether patients had secondary amyloidosis (HR=5.538, 95% CI 1.958-15.662, P=0.001) and whether patients received new drugs (HR=3.392, 95% CI 1.531-7.513, P=0.003) were independent factors associated with OS. We have investigated the presence of the MYD88^L265P and CXCR4^WHIM mutation in 34 patients and found that MYD88^L265P mutation was occurred in 32 patients (94.1%) and CXCR4^WHIM mutation was occurred in 8 patients (23.5%). Seven of 8 patients who harbored CXCR4^WHIM-mutated also exhibited the MYD88^L265P mutation. Patients with MYD88^L265PCXCR4^WHIM vs MYD88^L265PCXCR4^WT presented with more severe anemia, lower platelet level, higher M protein level and more hyper-viscosity syndrome. Conclusion WPSS risk group, whether patients had secondary amyloidosis or received new drugs are independent factors for OS in WM. MYD88^L265P and CXCR4^WHIM mutation, the most common somatic variants in WM, often occur together and impact the clinical presentation.