Objective:This study aimed to analyze the homology between carbapenem-resistant organisms (CRO) intestinal colonization strains and bloodstream infection (BSI) strains in patients undergoing hematopoietic stem cell transplantation (HSCT), confirming the clinical use of the real-time rectal swab Xpert Carba-R assay, and investigate its feasibility in early warning of BSI.Methods:Drug-resistant strains obtained from rectal swabs and blood culture samples of patients undergoing the same HSCT from January 2021 to December 2021 were collected and analyzed. The homology of the CRO intestinal colonization and BSI strains was confirmed using strain identification, antimicrobial resistance phenotyping, whole genome sequencing (WGS), multilocus sequence typing (MLST), and carbapenemase type identification. Rectal swab cultures and the real-time rectal swab Xpert Carba-R assay were conducted concurrently on patients with HSCT from August 2021 to August 2022. The accuracy of the real-time rectal swab Xpert Carba-R assay was confirmed with the sequencing results of polymerase chain reaction amplification products of the carbapenemase gene from purified colonies as a reference standard.Results:This study included 24 CRO strains from 10 patients undergoing HSCT, including 14 intestinal colonizers and 10 CRO-BSI strains. The results revealed that the CRO intestinal colonization strains and CRO-BSI strains from the same patient and their carbapenemase genes were almost identical. Additionally, WGS revealed that CRO intestinal colonization and CRO-BSI strains from the same patient were more closely related than strains from different patients. Additionally, this study included 488 rectal swab specimens from 184 patients undergoing HSCT, with CRO detection rates of 16.4% for rectal swab culture and 18.4% for the real-time rectal swab Xpert Carba-R assay. The overall sensitivity, specificity, and positive and negative predictive values of the real-time rectal swab Xpert Carba-R assay were 96.6%, 72.8%, 90.6%, and 88.9%, respectively.Conclusions:A high degree of homology was found between the CRO intestinal colonization strains and the CRO-BSI strains in patients undergoing HSCT. The real-time rectal swab Xpert Carba-R assay is a reliable and convenient method for detecting common carbapenemase genes, serving as an alternative to rectal swab culture for early warning of CRO-BSI.

Objective:This study aimed to analyze the homology between carbapenem-resistant organisms (CRO) intestinal colonization strains and bloodstream infection (BSI) strains in patients undergoing hematopoietic stem cell transplantation (HSCT), confirming the clinical use of the real-time rectal swab Xpert Carba-R assay, and investigate its feasibility in early warning of BSI.Methods:Drug-resistant strains obtained from rectal swabs and blood culture samples of patients undergoing the same HSCT from January 2021 to December 2021 were collected and analyzed. The homology of the CRO intestinal colonization and BSI strains was confirmed using strain identification, antimicrobial resistance phenotyping, whole genome sequencing (WGS), multilocus sequence typing (MLST), and carbapenemase type identification. Rectal swab cultures and the real-time rectal swab Xpert Carba-R assay were conducted concurrently on patients with HSCT from August 2021 to August 2022. The accuracy of the real-time rectal swab Xpert Carba-R assay was confirmed with the sequencing results of polymerase chain reaction amplification products of the carbapenemase gene from purified colonies as a reference standard.Results:This study included 24 CRO strains from 10 patients undergoing HSCT, including 14 intestinal colonizers and 10 CRO-BSI strains. The results revealed that the CRO intestinal colonization strains and CRO-BSI strains from the same patient and their carbapenemase genes were almost identical. Additionally, WGS revealed that CRO intestinal colonization and CRO-BSI strains from the same patient were more closely related than strains from different patients. Additionally, this study included 488 rectal swab specimens from 184 patients undergoing HSCT, with CRO detection rates of 16.4% for rectal swab culture and 18.4% for the real-time rectal swab Xpert Carba-R assay. The overall sensitivity, specificity, and positive and negative predictive values of the real-time rectal swab Xpert Carba-R assay were 96.6%, 72.8%, 90.6%, and 88.9%, respectively.Conclusions:A high degree of homology was found between the CRO intestinal colonization strains and the CRO-BSI strains in patients undergoing HSCT. The real-time rectal swab Xpert Carba-R assay is a reliable and convenient method for detecting common carbapenemase genes, serving as an alternative to rectal swab culture for early warning of CRO-BSI.

Objective:To explore the strategies of reducing relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk myelodysplastic syndrome (MDS) from the perspectives of optimizing the conditioning regimen and pre-transplant cytoreductive therapy.Methods:A total of 84 patients with high-risk MDS undergoing allo-HSCT between January 2013 and September 2019 were retrospectively analyzed. Based upon preparative regimens, they were divided into two groups of decitabine intensified BUCY2 ( n=49) and BUCY2 regimen ( n=35), based upon whether or not pre-treatment prior to allo-HSCT: cytoredutive treatment ( n=34) and none ( n=50). Two groups were compared with regards to hematopoietic reconstitution, graft-versus-host disease (GVHD), relapse rate, transplant-related mortality (TRM) and survival. Results:No significant inter-group differences existed in hematopoietic reconstitution or acute/chronic GVHD. The relapse rate was significantly lower in decitabine intensified group than that in BUCY2 group (18.7% vs 40.0%, P=0.025). Survival was significantly better in decitabine intensified group than that in BUCY2 group (3-year OS: 71.3% vs 51.2%, P=0.038; 3-year DFS: 65.3% vs 45.2%, P=0.033). Moreover, the incidence of recurrence was markedly lower in pre-transplant treatment group than that in non-treatment group (20.7% vs 38.9%, P=0.035). The inter-group incidence of TRM was not different. Three-year OS/DFS of treatment group were remarkably superior to those of non-treatment group (71.2% vs 50.8%, P=0.024; 64.7% vs 45.9%, P=0.044). Conclusions:As an optimal conditioning regimen for high-risk MDS, decitabine intensified BUCY2 regimen could better eliminate tumor burden, remarkably lower relapse rate and improve OS after allo-HSCT. In addition, pre-transplant treatment significantly reduces relapse and offers benefit for OS after allo-HSCT. Therefore intensified conditioning regimen and pre-transplant treatment may be promising strategies of reducing relapse and improving survival for high-risk MDS. However, it still needs further confirmation from prospective randomized controlled trials.

Objective:To compare the clinical efficacy of different doses of rabbit antithymocyte globulin (rATG) in haplo-HSCT in the treatment of hematologic malignancies.Methods:Malignant hematological patients treated at our hospital from March 2013 to December 2018 were retrospectively analyzed. These patients were divided into three groups as per three doses of ATG (6 mg/kg, 7.5 mg/kg, and 9 mg/kg) in the conditioning regimens. The transplant outcomes were compared in terms of the occurrence of acute graft versus host disease (GVHD) , infection, and survival.Results:①Total 288 patients were enrolled in the study, including 182 men and 106 women, with a median age of 18 (6-62) years. Total 110 patients were diagnosed with acute lymphoblastic leukemia (ALL) , 128 with acute myelogenous leukemia (AML) , 8 with chronic myeloid leukemia (CML) , 28 with myelodysplastic syndrome (MDS) , and 14 with mixed cell leukemia (MAL) . There were 159 patients in the ATG-6 group, 72 in the ATG-7.5 group, and 57 in the ATG-9 group. The median follow-up time of post transplantation was 14 (0.2-74) months. ②The incidence of neutrophil engraftment (96.9% , 97.2% , and 96.5% , respectively) and platelet engraftment (92.5% , 87.5% , and 86% , respectively) did not significantly differ among the ATG-6, ATG-7.5, and ATG-9 groups ( P=0.972, P=0.276) . The incidence of grades 2-4 acute GVHD was 14.5% , 11.1% , and 8.8% in the three groups, respectively ( P=0.493) , chronic GVHD incidence in the three group was 8.8% , 14.3% and 12.0% , respectively ( P=0.493) . The infection rates of CMV and EBV in the ATG-9 group (77.2% and 12.5% ) were significantly higher than those in the ATG-6 (43.3% and 3.5% ) , and ATG -7.5 group (44.4% and 1.5% ) ( P<0.001 and P=0.033, respectively) . ③Among the three groups, there were no significant difference in the 3-year overall survival [68.5% (95% CI 60.3% -77.9% ) , 60.1% (95% CI 48.3% -74.8% ) , 64.7% (95% CI 51.9% -80.7% ) ], cumulative incidences of relapse [34.6% (95% CI 34.3% -35.1% ) , 38.0% (95% CI 37.3% -38.7% ) , 20.6% (95% CI 20.0% -21.3% ) ], disease-free survival [53.3% (95% CI 44.9% -63.4% ) , 51.9% (95% CI 41% -65.8% ) , 63.9% (95% CI 51.9% -78.7% ) ] and non-relapse mortality [24.2% (95% CI 23.8% -24.5% ) , 26.0% (95% CI 25.4% -26.6% ) , 23.6% (95% CI 26.3% -28.2% ) ] ( P=0.648, P=0.165, and P=0.486 and P=0.955) . Conclusion:Low dose (6 mg/kg) of rATG may increase the risk of grade Ⅱ-Ⅳ aGVHD, and a high dose (9 mg/kg) of ATG could significantly increase the risk of CMV and EBV infection. Median dose (7.5 mg/kg) of ATG is expected to reduce the incidence of moderate to severe aGVHD and viral infections without increasing the mortality.

Objective To explore the role of cerebrospinal fluid chimerism in central nervous relapse surveillance for patients of acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The follow-up data were retrospectively collected and analyzed in 104 patients with acute leukemia after allo-HSCT.Comparisons were made between patients with complete chimerism and mixed chimerism in cerebrospinal fluid.The role of recipient DNA percentage and its changing trend in predicting central nervous relapse were also explored.Analysis was conducted for determining the risk factors of central nervous relapse.And the effectiveness of prophylaxis with intrathecal injection was also examined.Results The incidence of relapse was higher in patients with mixed chimerism (P＜0.001),high percentage of recipient DNA (P＜0.05) and higher mixed chimerism (P＜0.001).Hyperleukocytosis at an initial diagnosis was a risk factor of central nervous relapse.Whether or not intrathecal injection prophylaxis was applied showed no significant difference in relapsing rate.Conclusions Monitoring cerebrospinal fluid chimerism can effectively help predict central nervous relapse among patients of acute leukemia after allo-HSCT.Yet intrathecal injection prophylaxis failed to benefit recipients.

Objective To observe the anti-relapse and anti-graft versus host disease (GVHD) effects and side effects of ruxolitinib on patients who have relapsed leukemia after allo-hematopoietic stem cell transplantation (HSCT).Methods The clinical data of four patients sufferring from relapsed leukemia were collected and analyzed retrospectively.Three cases had a positive gene and 1 case had a extramedullary recurrence.All of them had serious GVHD involving multiparts,as the result of attenuating immunosuppressant aggressively.One case had central nervous system leukemia before allo-HSCT.Those patients were treated with ruxolitinib,according to the degree of GVHD,the treatment strategy and curative effect of GVHD,and the residual condition of original leukemia.Then,the degree of GVHD,the residual condition of original leukemia and the side effects of ruxolitinib were revaluated once a month after taking ruxolitinib.Results One case achieved completer remission (CR) and there partial remission (PR) in consideration of GVHD.Up to date,2 cases had no relapse in any level and 2 cases replased according to any of the results related to bone marrow aspiration.Conclusion Ruxolitinib is effective in patients with GVHD after allo-HSCT and doesn't influence GVL effect or increase the risk of relapse at the same time.Ruxolitinib doesn't have obvious side effects when treating GVHD.

Objective To analyze the motivation of Chinese patients with chronic myelogenous leukemia (CML) who have stopped the tyrosine kinase inhibitor (TKI). Methods Forty-seven CML patients who have stopped TKI provided informed consent prior to their participation in the study. These patients were divided into relapse and non-relapse group at the endpoint of the observation. None of the patients received any CML-associated therapies after TKI cessation. The reasons of withdrawal were analyzed statistically. Results The reasons for cessation included patient's request due to cost(59.57 %, 28/47), patient's plan to getting pregnant(8.52 %,4/47),side-effect of TKI(23.40 %,11/47)and other reasons(8.52 %,4/47).At the endpoint of observation, 23 patients suffered molecular relapse. Among them, 15 cases (65.22 %) were due to cost; 1 case (4.35 %) was due to getting pregnant, 5 cases (21.74 %) were due to side-effect and 2 cases (8.69 %) were due to other reasons. There was more frequency relapse in the group of insufficient cost. Conclusion The motivation of Chinese CML patients who have stopped TKI might show impact on the outcome,and the motivation is mainly related with history of drug reduction and withdrawal.

Objective We used the dataset base on high throughput sequencing data to construct a diagnosis model by ANN and GA.Methods We screened the Taylor_prostate datasets from GEO according to,then we used the GA to screen the datas further. Finally we used the ANN to analyze the datas and construct a diagnosis model. To validate the model,we used 10-folds crossvalidation as the inner validation and the datas from Grasso dataset( GPL6480 and GPL6848) were used as the outter validation.Results We got 5 genes ACADL,ACTG2, CACNA2D1,PCP4 and SPARCL1.And we used spss to get the AUC of the model which is 94.62.The result of validation is good.Conclusion The performance of the model is good because the AUC is larger than 0.5.

Objective To explore the value of retinoblastoma binding protein 4 ( RBBP4 ) in diagnosing prostate cancer ( PCa).Methods From January 2015 to December 2015, the prostate tissue after prostatectomy were collected and the differentially expressed degree of RBBP4 protein was analyzed in PCa and adjacent tissues by 2D-DIGE technology.The RBBP4 score of prostate tissue chip which contains 3 normal prostate tissues, 7 cancer adjacent normal prostate tissues, 50 adenocarcinoma and 20 hyperplasia tissue was checked by immunohistochemistry( IHC).In 50 patients with PCa, 4 cases were less than 60 years old and 46 cases were more than 60 years.In those patients, the Gleason scores were less than 7 scores in 18 cases, and more than 7 scores in 30 cases.22 cases were confirmed less than Ⅱ stage, and 28 cases were confirmed more than Ⅲ stage.Finally, the RBBP4 IHC score and the clinic-pathological parameters such as age, Gleason score and clinical stage of PCa patients were analyzed together.Results We found that the protein of RBBP4 increased by 2.15 times in PCa tissues compared to adjacent tissues by using 2D-DIGE technology( P=0.008).The expression of RBBP4 was higher than that in benign tissues by IHC ( F=43.972,P=0.000).And the expression of RBBP4 was positive correlation with Gleason score( t=5.589, P=0.000) and clinical stage(t=5.620,P=0.000), but was negative correlation with age(t=1.125,P=0.266).Conclusions The detection of RBBP4 can help to separate PCa from benign tissues.The overexpression of RBBP4 might result in the rapid growth of malignant cells.It may have certain value in determine the clinical staging and pathological grading of PCa.

OBJECTIVETo exam the role of leukemia cells-derived microparticles in the post-complete molecular response stratification.

METHODSBlood samples from 29 patients diagnosed with chronic myeloid leukemia (CML) were collected. Microparticles (MP) were extracted from the peripheral blood. Real-time PCR was performed to measure the level of BCR-ABL mRNA.

RESULTSBCR-ABL mRNA could be stably detected both in MP and peripheral blood cells; BCR-ABL in MP showed significant difference within complete molecular response, major molecular response and complete cytogenetic response (9.1±2.8, 25.2±6.9 and 62.8±6.3 respectively, P<0.05). BCR-ABL was detected in MP even when it was negative in peripheral blood cells (3.7-15.3). For patients with complete molecular response, BCR-ABL in MP but not cells were significantly different between imatinib and stem cell transplant recipients (3.3±2.1 vs 9.1±2.8, P<0.05).

CONCLUSIONThis study indicated that MP may serves as a new target for monitoring of CML. Quantification of BCR-ABL in MP may offer a novel strategy for stratification of molecular response.

Adolescent ; Adult ; Cell-Derived Microparticles ; Child ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; therapy ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Real-Time Polymerase Chain Reaction ; Young Adult