Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.

Objective To explore the efficacy of hematopoietic stem cell transplantation (HSCT) for 5 patients with Ph-like acute lymphoblastic leukemia (ALL).Methods Fluorescent in situ hybridization (FISH) was performed for detecting the rearrangement of susceptibility genes.Combined therapy of chemotherapy and ruxolitinib were applied,followed by HSCT.Those failing to achieve complete remission (CR) received an infusion of chimeric antigen T-cells (CAR-T),followed by HSCT once CR was achieved.Four patients accept allogenic HSCT while another auto HSCT.Results Three of them achieved CR after chemotherapy and ruxolitinib.The remaining 2 patients got CR after CAR-T.Four patients remained in CR after HSCT.Early relapse occurred in 1 patient after HSCT.Conclusions Combined therapy of chemotherapy,ruxolitinib and CAR-T are necessary for Phlike ALL patients.HSCT after an initial CR improve patient prognosis.

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C_trough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers’ group (30 cases) and poor metabolizers’ group (35 cases). The C_trough of the 65 patients were detected for 169 times totally, and there was a significant difference of C_trough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of C_trough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ²=11.689, P=0.020). Conclusion Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C_trough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.

Objective To investigate the status and influencing factors of infusion-related adverse events in third-party cord blood stem cell infusion. Methods A total of 305 patients successfully underwent haploidentical stem cell transplantation combined with the third-party cord blood(CB) infusion,were recruited by convenience sampling from January 2013 to December 2015,in hematological department of a tertiary hospital in Suzhou. A self-developed questionnaire and adverse event assessment scale were used to investigate the influencing factors. Results The rate of infusion-related adverse events was 49.51%,81.82% were related to cardiovascular adverse events with the high-est rate of hypertension(76.14%). Logistic regression analysis showed that age(OR=1.030,95CI%:1.010-1.051),HLA matching between CB and receptor (OR=0.589,95%CI:0.413-0.838),thawed CB cell activity (OR=1.064,95%CI:1.015-1.115)were major influencing factors. Conclusion Nurses should pay attention to patients who are elderly,with low matching HLA and receive thawed CB product with high cell activities,and provide timely nursing care in advance.

OBJECTIVE:To reduce the error rate of homing the withdrawn drugs in pharmacy intravenous admixture service (PIVAS). METHODS:Using risk priority(RPN),the potential failure modes for links of homing the withdrawn drugs in PIVAS were evaluated by using failure mode and effects analysis (FMEA) method. Combining with the links of homing the withdrawn drugs,the reasons for errors were investigated,the feasible scheme to reduce error rates was proposed and the intervention effect was evaluated after 3 months. RESULTS:In the PIVAS links of homing the withdrawn drugs,8 high-risk failure modes had been found in total,such as poor double check system(RPN was 100),unfamiliarity of seemingly drugs(RPN was 36),a large num-ber of the withdrawn drugs(RPN was 20),etc. Thus,risk control measures had been formulated,including reinforcing the double check system,optimizing the management system of PIVAS and so on. After 3 months of intervention management,RPN of the first 3 items were reduced to 20,16,8;error rate of homing the withdrawn drugs was reduced from 1.98% to 0.62%(P<0.05). CONCLUSIONS:The application of FMEA management method in PIVAS of our hospital has reduced the error rate of homing the withdrawn drugs.

OBJECTIVE Discuss the cooperative relationship between The Office of Nosocomial Infection Control("the Office") and the Center for Disease Control and Prevention("the Center") in hospital.METHODS The cooperative relationship between the Office of Nosocomial Infection Control and the Center were analyzed,the third degree A Class hospitals in Beijing area.RESULTS 25 hospitals had set up Centers.Among them,there are special stuff in charge of the report of the infection in 17 hospitals which had the Office with the function of the Center.So far,none of the Offices with the function of the Center can operate all the functions of the office.CONCLUSIONS The setup of the Center is to detect and control infectious disease on the basis of nosocomial infection control.