[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Analysis of the characteristics of retracted scientific papers in the field of global liver diseases published by Chinese scholars].

Objective: To analyze the characteristics of scientific papers in the field of global liver diseases published by Chinese scholars that were retracted for diverse reasons from the Retraction Watch database, so as to provide a reference to publishing-related papers. Methods: The Retraction Watch database was retrieved for retracted papers in the field of global liver disease published by Chinese scholars from March 1, 2008 to January 28, 2021. The regional distribution, source journals, reasons for retraction, publication and retraction times, and others were analyzed. Results: A total of 101 retracted papers that were distributed across 21 provinces/cities were retrieved. Zhejiang area (n = 17) had the most retracted papers, followed by Shanghai (n = 14), and Beijing (n = 11). The vast majority were research papers (n = 95). The journal PLoS One had the highest number of retracted papers. In terms of time distribution, 2019 (n = 36) had the most retracted papers. 23 papers, accounting for 8.3% of all retractions, were retracted owing to journal or publisher concerns. Liver cancer (34%), liver transplantation (16%), hepatitis (14%), and others were the main areas of retracted papers. Conclusion: Chinese scholars have a large number of retracted articles in the field of global liver diseases. A journal or publisher chooses to retract a manuscript after investigating and discovering more flawed problems, which, however, require further support, revision, and supervision from the editorial and academic circles.

Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

[Molecular studies on parental origin and cell stage of nondisjunction in sex chromosome aneuploidies].

To study the parental origin and cell stage of nondisjunction in sex chromosome aneuploidies. Retrospectiving and analyzing the results of 385 cases of SCA confirmed by QF-PCR and karyotype analysis in the prenatal diagnosis center of Guangzhou Women and Children Medical Center from January 2015 to December 2020. The types of samples and prenatal diagnosis indications were analyzed. The parental origin and cell stage of nondisjunction in sex chromosome aneuploidies analyzed by comparing the short tandem repeat (STR) peak patterns of samples from fetuses and maternal peripheral blood. The results show that (1) There were 324 cases of nonmosaic SCA, 113 cases (113/324, 34.9%) were 45, XO, 118 cases (118/324, 36.4%) were 47, XXY, 48 cases (48/324, 14.8%) were 47, XXX and 45 cases (45/324, 13.9%) were 47, XYY. 68 (45/324, 60.2%) cases of 45, X were detected in villus samples. The other SCA cases were mainly detected in amniotic fluid samples. There were 61 mosaic SCA samples, 58(58/61, 95.1%) of mosaic SCA samples were mosaic 45, X. (2) The top two indications of 45, X cases are increased nuchal translucency(53/113, 46.9%) and fetal cystic hygroma (41/113, 36.3%), while the most common indication of other types of SCA was high risk of NIPT(170/272, 62.5%). (3) Among 45, X cases, there were 88 cases (88/113, 77.9%) inherit their single X chromosome from their mother and 25 cases (25/119, 22.1%) from their father. In 47, XXY samples, 47 cases (47/118, 39.8%) of chromosome nondisjunction occurred in meiosis stage Ⅰ of oocytes, 51 cases (51/118, 43.2%) occurred in meiosis stage Ⅰ of spermatocytes, and 20 cases (20/118, 16.9%) occurred in meiosis stage Ⅱ of oocytes. Among 47, XXX samples, 29 cases (29/48, 60.4%) of X chromosome nondisjunction occurred in meiosis stage Ⅰof oocytes, 15 cases (15/48, 31.3%) occurred in meiosis stage Ⅱ of oocytes, and 4 cases (4/48, 8.3%) occurred in meiosis stage Ⅱ of spermatocytes. In summary, the cases of 45, X were mainly diagnosed by villous samples for abnormal ultrasound findings. The other cases of SCA were mainly diagnosed by amniocentesis samples for abnormal NIPT results. Different types of SCA, the origin and occurrence period of sex chromosome nondisjunction were different.

[Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines].

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

[Epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019].

Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female (P=0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z=1.769, P=0.049), and the strongest correlation in 2016 (Moran's I=0.328, Z=4.979, P=0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.

[Efficacy and safety of conformal thermocoagulation guided by stereotactic electroencephalogram in the treatment of epilepsy caused by focal cortical dysplasia in eloquent cortex].

Objective: To explore the efficacy and safety of stereotactic electroencephalography (SEEG)-guided conformal radiofrequency thermocoagulation for epilepsy caused by focal cortical dysplasia (FCD) in eloquent cortex. Methods: The data of epilepsy patients with conformal thermocoagulation in the Epilepsy Center of Guangdong Sanjiu Brain Hospital from September 2017 to August 2020 were retrospectively analyzed. SEEG electrodes were placed in patients with drug-refractory epilepsy caused by FCD in eloquent cortex with limited boundaries, which was confirmed by preoperative evaluation methods such as imaging and electroencephalography. When designing the electrode placement plan, related software was used to reconstruct the three-dimensional MRI image and lesion. SEEG electrode contacts should be designed to fully cover the lesion as much as possible. After the completion of SEEG monitoring and cortical electrical stimulation, the pre-thermocoagulation and permanent thermocoagulation modes were used in sequence. The mode of direct damage between adjacent contacts of a single electrode and cross-destruction between adjacent contacts of multiple electrodes was combined to ablate the lesions point by point. Results: A total of 22 patients were enrolled, ranging from 2 to 30 years old, with an average age of (15±9) years old. MRI showed that FCD lesions located at pre-central gyrus in 19 cases, at post-central gyrus in 3 cases, at left frontal lobe in 3 cases, at both pre-central and post-central gyrus in 1 case and at both pre-central and left frontal lobe in 2 cases. The length of the lesion was 1.2-4.0 cm, with an average length of (2.2±0.7) cm. Moreover, 7-12 SEEG electrodes were implanted, with an average of (9±2) electrodes. The number of electrodes passing through the lesion was 2-8, with an average of 5±2. The number of thermocoagulation target points was 6 to 83, with an average of 29±18, while the number of target points which proved to have function by cortical simulation was 0-21, with a median of 3.5. The number of direct thermocoagulation target points was 6 to 58, with an average of 23±13, while the number of cross thermocoagulation target points was 0 to 30, with a median of 3. The completion of the whole thermocoagulation was divided into 2 to 5 times. There were 11 cases (50%) who experienced immediate muscle strength decline, 1 case (4.5%) showed slower speech speed during thermocoagulation, 3 cases (13.6%) exhibited muscle strength decline after thermocoagulation, however, only 1 case (4.5%) had permanent hemiparalysis. There were 17 cases of Engel Ⅰ (77.3%), 3 cases of Engel Ⅱ (13.6%), and 2 case of Engel Ⅲ (9.1%), respectively, after follow-up for 6-42 months, with an average of (20±10) months. Conclusion: SEEG-guided conformal radiofrequency thermocoagulation is safe and effective for epilepsy caused by FCD in eloquent cortex with limited boundaries.

[Immunogenicity and safety of concomitant inoculation of Measles and rubella combined live vaccine and Japanese encephalitis attenuated live vaccine].

Objective: To evaluate the immunogenicity and safety of concomitant inoculation of Measles and Rubella Combined Live-attenuated Japanese encephalitis vaccine. Methods: Healthy children aged 8 months in selected cities in Zhejiang Province were randomly assigned to the MR and JVE-L combined vaccination group (the experimental group), and the MR single vaccination group (the control group) was taken before the exemption and 6 weeks after the exemption. Peripheral venous blood 1 ml was used as serum antibody test for measles and rubella, and the levels of measles and rubella antibodies before and after vaccination were evaluated. The safety of combined vaccination was evaluated. Measles and rubella IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Data were double-entry with Epidata and statistical analysis was performed using Epi Info epidemiological statistical analysis software. Results: The results showed that no severe adverse event occurred in two groups, clinical reactions in each inoculation group were mild.The seroconversion rate of measles antibody and rubella antibody were 96.43% and 88.49% in the experimental group after vaccination, the geometrical mean concentrations(GMC) of measles antibody was 1 526.45 mIU/ml and the GMC of rubella antibody was 47.70 mIU/ml after concomitant inoculation; the seroconversion rate of measles antibody and rubella antibody were 97.62% and 86.11% in the control group, the GMC of Measles antibody was 1 392.28 mIU/ml and the GMC of Rubella antibody was 45.72 mIU/ml after MV inoculation. No difference were detected in two groups of seroconversion rate of measles antibody and rubella antibody and GMC after vaccination. Conclusion: The immunogenicity and safety is equivalent when MR and JVE-L were simultaneous inoculation.

[Anti-CD(25) monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease in 80 patients receiving allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of anti-CD(25) monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 20l6 were enrolled in this study. Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8). Anti-CD(25) monoclonal antibodys (mAb) were administrated on days 1, 4, 8, 15, and 22. The efficacy of anti-CD(25) mAb was evaluated at day 28 after the initial treatment. The associated factors of clinical outcome were analyzed. Results: The overall response (OR) rate of anti-CD(25) mAb was 75% (60/80), with complete response (CR) rate, partial response (PR) rate and no response(NR) rate 52.5% (42/80), 22.5% (18/80), and 25% (20/80), respectively. GVHD-relapse was not observed with a median follow-up time of 394.5 days (range, 12-1 761 days). The 6-month overall survival (OS) rate was 68.4%(95%CI 63.2%-73.6%). The 1-year OS rate was 63.1% (95%CI 57.6%-68.6%), and 2-years OS rate was 50.7% (95%CI 44.3%-57.1%). Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6% (95%CI 27.2%-38%) and 41.7% (95%CI 35.3%-48.1%), respectively. The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9% (95%CI 26.4%-39.4%) and 38.9% (95%CI 31.8%-46.0%). By univariate and multivariate analysis, liver involvement was an independent poor risk factor of SR-aGVHD (OR=4.66, 95%CI 1.145-18.962, P=0.032). Conclusion: Anti-CD(25) mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present. Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.

[Antibody persistence following on different vaccination strategies of domestic measles, mumps and rubella combined attenuated live vaccine: a 3-year follow-up study].

Objective: To assess the 3-year antibody persistence after vaccination of domestic measles, mumps and rubella combined attenuated live vaccine (MMR) with different program. Methods: Children from three different vaccination strategies (Group 8 m MR: 8 months and 18 months vaccinated with measles-rubella combined attenuated live vaccine and domestic MMR,respectively; Group 8 m MMR: 8 months and 18 months both vaccinated with domestic MMR; Group 12 m MMR: 12 months and 22 months both vaccinated with domestic MMR ) were followed up in Zhejiang province in July 2015. There were 170 participants in Group 8 m MR, 171 participants in Group 8 m MMR and 173 participants in Group 12 m MMR selected by simple random sampling method .Blood samples (venous blood 2-3 ml) were collected 1 month after the first dose vaccination of MMR (only in Group 8 m MMR and Group 12 m MMR) and 3 years (36-38 months) after the last dose vaccination of MMR and tested for antibody IgG against Measles, Mumps and Rubella using ELISA. Seropostive rate and Geometric mean concentration (GMC) were calculated and compared among different groups by Chi-square test or Fisher exact test and Kruskal-Wallis H test. Results: A total of 514 participants (8 m MR: 170; 8 m MMR:171; 12 m MMR:173) were enrolled. The overall seropositivity rate of measles, mumps and rubella was 98.1% (504), 93.4% (480) and 88.1% (453), respectively, with corresponding GMC was 1 012.33 mU/ml, 502.87 U/ml and 50.53 U/ml respectively. There was no significant difference of seropositivity rate for measles among three groups (all groups were>97%). The highest seropositivity rate for mumps was found in the Group 12 m MMR with the rate of 98.8% (171/173), followed by Group 8 m MMR and Group 8 m MR with 93.0% (159/171) and 88.2%(150/170) respectively (Fisher exact test, P<0.001). The highest seropositivity rate for rubella was also found in the Group 12 m MMR with the rate of 94.8% (164/173), followed by Group 8 m MMR and Group 8 m MR with 86.6%(148/171) and 82.9%(141/170) respectively (Fisher exact test, P=0.002). The highest GMC of antibody against measles, mumps and rubella were all found in Group 12 m MMR, with 1 217.30 (1 119.35-1 323.82) mU/ml, 717.07 (643.83-798.65) U/ml and 62.54(56.21-69.58) U/ml respectively. The lowest GMC of antibody against measles and mumps were both in Group 12 m MR with 812.01 (734.52-897.67) mU/ml and 363.28 (305.42-432.11) U/ml respectively. The lowest GMC of antibody against rubella was in Group 8 m MMR with 44.10 (39.08-49.76) U/ml. These differences of GMCs among three groups were all reach significant means (P<0.05). Conclusion: High level seropostive rates and GMCs were exist against measles and rubella after 3-year vaccination of domestic MMR among different program. Higher antibody level against mumps were found in those children with two doses vaccination of MMR.

Endoscopic submucosal dissection for laterally spreading tumors in the rectum ≥40 mm.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been developed to allow en bloc resection of early neoplasia of the gastrointestinal tract, including colorectal tumors. The aim of the present study was to evaluate the safety and efficacy of ESD for laterally spreading tumors (LSTs) in the rectum with diameters of 40 mm or more. METHODS: Between January 2010 and October 2014, 35 patients with a total of 36 LSTs of the rectum measuring ≥40 mm were included in this study. Clinical and pathological characteristics and clinical outcomes were examined and analyzed. RESULTS: The mean operating time was 125.8 ± 61.4 min, and the mean size of the tumors was 59.4 ± 19.8 mm. The rate of en bloc resection and en bloc R0 resection were 91.7 % (33/36) and 88.9 % (32/36), respectively. Perforation occurred in three patients (8.6 %) and was managed conservatively. Postoperative bleeding occurred in one patient (2.9 %) and was treated by endoscopic hemostasis. Excluding five patients, who either underwent additional surgery (n = 1) or were lost to follow-up (n = 4), two patients in our cohort (6.7 %) presented with recurrence of a small adenoma. The remaining patients (n = 28) were free of recurrence during a mean follow-up period of 18.7 ± 4.2 months (range 12-43 months). CONCLUSIONS: Our results indicated that ESD is an effective and safe therapeutic option with high curative rates for LSTs in the rectum ≥40 mm. To prove its long-term efficacy, a large multicenter prospective study is required.

[Improved clinical outcome of acute myeloid leukemia with FLT3-ITD mutation treated with sorafenib].

OBJECTIVE: To analyze the efficacy of sorafenib on the treatment of patients diagnosed as acute myeloid leukemia(AML) with FLT3-ITD mutation. METHODS: From January 2012 to February 2015, 42 cases of AML with FLT3-ITD mutation according to MICM (morphology, immunology, cytogenetics and molecular) diagnosis system in our hospital were retrospectively analyzed. Thirty-two cases were refractory to chemotherapy or relapsed, who were treated with sorafenib or combined with chemotherapy. Ten patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were retreated with sorafenib or combined with donor lymphocyte infusion (DLI) or chemotherapy. In the first group, 13 of 32 patients accepted allo-HSCT. RESULTS: The overall response rate of all 42 patients was 73.8%, including 4 (9.5%) complete molecular remission (CMR), 9 (21.4%) complete remission (CR), 8 (19%) complete remission with incomplete hematologic recovery (CRi), 10 (23.8%) partial remission (PR), and 11 (26.2%) none remission (NR). The response rate of sorafenib alone for 17 patients was 70.6%, and that of sorafenib plus chemotherapy was 66.7% (P=0.555). Thirteen patients who received allo-HSCT included 6 CMR/CR/CRi, 4 PR, and 3 NR before transplant. The 2-year overall survival (OS) rate and progress free survival (PFS) rate in all patients were 36.9% and 28.7%, and the corresponding median time were 18 months and 9 months respectively. The 2-year OS rate in 23 patients who received sorafenib combined with allo-HSCT was superior to that in 19 patients not receiving allo-HSCT (45.5% vs 23.9%, P=0.041), so was PFS rate (44.0% vs 9.7%, P=0.014). Twelve cases died of disease progression, four of infection, and one of chronic graft versus host disease after transplant. CONCLUSIONS: Sorafenib combined with chemotherapy improves response rate of AML patients with FLT3-ITD mutation. Those who are treated with sorafenib plus allo-HSCT obtain better long-term survival.

Identification of a novel HLA-DRB1 allele, HLA-DRB1*12:51, in a Chinese Cord Blood Donor.

HLA-DRB1*12:51 has a single nucleotide difference to DRB1*12:02:01 at position 208, G > T.

[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

[The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia].

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

[Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection].

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

[Evaluating the real-world vaccine effectiveness using a regression discontinuity design].

Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.

[Clinical analysis of amphotericin B cholesteryl sulfate complex for injection in the treatment of invasive fungal disease for patients with hematological malignancies in 30 cases].

Objective: To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness. Methods: This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives. Results: 30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day. Conclusions: Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

[Clinical and prognostic values of TP53 mutation in patients with B-lineage acute lymphoblastic leukemia].

Objective: To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation. Methods: The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed. Results: Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different (P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant (P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant (χ(2)= 4.694, P = 0.030; χ(2)= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR(1) state, and 2 patients with recurrence after transplantation obtained CR(2) after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion: Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.