Mortality and serum hepcidin are associated with persistent and transient acute kidney injury in septic patients.

PURPOSE: Acute kidney injury (AKI) is a common complication of sepsis and has high mortality. The 2017 Acute Disease Quality Initiative (AQDI) workgroup proposed new definitions for AKI - transient AKI and persistent AKI; however, very little is known about the effect of transient and persistent septic AKI on short-term mortality among critically ill patients with sepsis. The purpose of this study was to assess the impact of persistent AKI on mortality and to evaluate whether serum hepcidin can predict the occurrence of persistent AKI in critically ill patients with sepsis. MATERIALS AND METHODS: This prospective observational study was performed in a general hospital mixed surgical-medical ICU in Pudong, China. Consecutive adults with sepsis admitted to the ICU with absence of chronic kidney disease, renal transplant, and AKI were included. AKI was defined according to the KDIGO criteria and classified as transient (< 48-hour duration) or persistent (48-hour duration). Blood samples were obtained within 6 hours from when AKI was diagnosed. RESULTS: A total of 90 patients with sepsis or septic shock were included in the analysis. 44 (48.89%) patients developed AKI during ICU stay: 20 (45.45%) had transient and 24 (54.55%) had persistent AKI. Persistent AKI has a higher mortality than transient AKI (66.7 vs. 30.0%, p = 0.002). Persistent AKI and sequential organ failure assessment (SOFA) scores were an independent predictor of 60-day mortality. Patients with persistent AKI had higher concentrations of serum creatinine (SCr) and hepcidin than transient AKI patients when AKI was diagnosed. Logistic regression indicated that serum hepcidin was an independent predictor of persistent AKI in septic patients, with a fairly predictive value (AUC 0.71, 95% CI: 0.47 - 0.87; p = 0.02). CONCLUSION: Persistent AKI was associated with increased 60-day mortality compared with transient AKI in septic patients. The serum hepcidin levels measured when AKI was diagnosed have a fair predictive value to predict the occurrence of persistent AKI in septic patients.

Kinetic changes in serum procalcitonin predict persistent acute kidney injury in critical patients.

PURPOSE: Persistent acute kidney injury (AKI) has been shown to be closely associated with poor prognosis in critical patients. Recent studies have shown that procalcitonin (PCT) is valuable for the early prediction of AKI in critically patients. Our aim was to determine whether PCT and its kinetic changes could predict the occurrence of persistent AKI in critical patients. METHODS: This is a prospective observational study. The definition of AKI was based on the Kidney Disease: Improving Global Outcomes criteria. Persistent AKI was defined as renal function that does not return to baseline serum creatinine levels within 48 h. Blood samples were obtained at the onset of AKI and two subsequent days of hospital stay. 24-h PCT change (ΔPCT-24 h) was defined as 24 h PCT minus baseline PCT (day 0). RESULTS: A total of 91 critical patients with AKI were included in this study. The persistent AKI group had a stepwise increase in PCT concentration. ΔPCT-24 h was higher in the persistent AKI group (p < .01). Logistic regression analysis showed that ΔPCT-24 h (p = .04) was independent predictors of persistent AKI. The receiver operating characteristic curves showed that area under the curve of ΔPCT-24 h was 0.84 (p < .01), and the cut-off value for PCT to predict persistent AKI was 0.56 ng/ml. CONCLUSION: Our study showed that the observation of kinetic changes in PCT is more significant for the early prediction of persistent AKI than the index of PCT at a single time point. ΔPCT-24 h is a good predictor of persistent AKI in critical patients.

[The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning].

OBJECTIVE: To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning. METHODS: In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope. RESULTS: Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels. CONCLUSION: The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.

Combination of hepcidin with neutrophil gelatinase-associated lipocalin for prediction of the development of sepsis-induced acute kidney injury.

BACKGROUND AND AIMS: The early prediction of the development of acute kidney injury (AKI) in critically ill patients with sepsis would facilitate early effective intervention. Recently, interest has focused on the biomarkers for AKI-linked iron metabolism. This study aimed to assess the early predictive values of hepcidin, neutrophil gelatinase-associated lipocalin (NGAL), and their combination for secondary AKI in patients with sepsis. MATERIALS AND METHODS: A prospective cohort study was performed in septic patients. Serum and urine hepcidin, and urine NGAL were analyzed at admission. The primary outcome measure was occurrence of sepsis-induced AKI based on 2011 Kidney Disease: Improving Global Outcomes (KDIGO) criteria during the first week of ICU stay. RESULTS: Of the 90 patients analyzed finally in the study, 44 (48.9%) patients developed AKI. Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and urine NGAL levels at admission (P < 0.01). Higher concentrations of these biomarkers were each independent predictor of the development of AKI in critically septic patients within the first week of their ICU stay. Serum hepcidin and urine NGAL (AUROC 0.787, 95% CI 0.688 to 0.8660 and AUROC 0.729, 95% CI 0.625 to 0.818, respectively) were comparable predictive indicators of AKI occurrence (P = 0.43 for DeLong's test). Combining both biomarkers increased the AUROC to 0.828(95% CI 0.733 to 0.899), and this performance was statistically significantly better than urine NGAL alone (P = 0.03 for DeLong's test). CONCLUSION: Serum hepcidin measured at admission predicts the development of AKI similarly to urine NGAL. However, serum hepcidin adds significant accuracy to this prediction in combination with urine NGAL alone and has a good predictive value in patients with sepsis. Larger studies are needed to validate and explain these findings.

A Combined Phytochemistry and Network Pharmacology Approach to Reveal Potential Anti-NSCLC Effective Substances and Mechanisms in Marsdenia tenacissima (Roxb.) Moon (Stem).

Marsdeniae tenacissimae Caulis is a traditional Chinese medicine, named Tongguanteng (TGT), that is often used for the adjuvant treatment of cancer. In our previous study, we reported that an ethyl acetate extract of TGT had inhibitory effects against adenocarcinoma A549 cells growth. To identify the components of TGT with anti-tumor activity and to elucidate their underlying mechanisms of action, we developed a technique for isolating compounds, which was then followed by cytotoxicity screening, network pharmacology analysis, and cellular and molecular experiments. We isolated a total of 19 compounds from a TGT ethyl acetate extract. Two novel steroidal saponins were assessed using an ultra-performance liquid chromatography-photodiode array coupled with quadrupole time-of-flight mass (UPLC-ESI-Q/TOF-MS). Then, we screened these constituents for anti-cancer activity against non-small cell lung cancer (NSCLC) in vitro and obtained six target compounds. Furthermore, a compound-target-pathway network of these six bioactive ingredients was constructed to elucidate the potential pathways that controlled anticancer effects. Approximately 205 putative targets that were associated with TGT, as well as 270 putative targets that were related to NSCLC, were obtained from online databases and target prediction software. Protein-protein interaction networks for drugs as well as disease putative targets were generated, and 18 candidate targets were detected based on topological features. In addition, pathway enrichment analysis was performed to identify related pathways, including PI3K/AKT, VEGF, and EGFR tyrosine kinase inhibitor resistance, which are all related to metabolic processes and intrinsic apoptotic pathways involving reactive oxygen species (ROS). Then, various cellular experiments were conducted to validate drug-target mechanisms that had been predicted using network pharmacology analysis. The experimental results showed the four C21 steroidal saponins could upregulate Bax and downregulate Bcl-2 expression, thereby changing the mitochondrial membrane potential, producing ROS, and releasing cytochrome C, which finally activated caspase-3, caspase-9, and caspase-8, all of which induced apoptosis in A549 cells. In addition, these components also downregulated the expression of MMP-2 and MMP-9 proteins, further weakening their degradation of extracellular matrix components and type IV collagen, and inhibiting the migration and invasion of A549 cells. Our study elucidated the chemical composition and underlying anti-tumor mechanism of TGT, which may be utilized in the treatment of lung cancer.

Prediction of in-hospital recurrence and false-negative results in patients with COVID-19 by red blood cell values on admission.

The clinical characteristics and risk factors of patients with coronavirus disease 2019 (COVID-19) with re-positive or false-negative test results have so far remained to be determined. The present study provides a cross-sectional observational study on 134 hospitalized patients selected from Huoshenshan Hospital (Wuhan, China) using cluster sampling. A total of 68 patients had reduced red blood cell (RBC) counts, 55 a decrease in the hemoglobin concentration (HBC) and 73 a decline in hematocrit (HCT). The false-negative rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA detection in pharyngeal swab specimens was 18.7%. The absolute lymphocyte count (ALC), RBC, HBC and HCT levels in false-negative patients were significantly higher than those in patients who tested positive for viral nucleic acids. Multivariate logistic regression analysis indicated that RBC [odds ratio (OR)=0.43, 95% CI: 0.18-0.99], HBC (OR=0.97, 95% CI: 0.94-0.99) and ALC (OR=0.43, 95% CI: 0.20-0.91) were the factors influencing the negative testing results for viral nucleic acid. The rate of re-positive patients was 16.4%. The white blood cell, RBC, HBC and HCT values in re-positive patients were lower than those in non-re-positive patients. The median (interquartile range) values for RBC, HBC and HCT of male re-positive patients were 3.95 (3.37, 4.2) x1012/l, 123 (103, 133) g/l and 36.6 (31.1, 39.2)%, respectively, while the RBC, HBC and HCT of female re-positive patients were 3.54 (3.13, 3.74) x1012/l, 115 (102, 118) g/l and 34.2 (28.5, 34.9)%, respectively. It was determined that RBC, HBC and HCT values had moderate accuracy in predicting SARS-CoV-2 recurrence in patients with COVID-19 using receiver operating curve analysis. The present study suggested that RBC may have an important role in the pathogenesis of COVID-19.

Nomogram predicting pulmonary metastasis of hepatocellular carcinoma after liver transplantation.

A novel prognostic nomogram predicting post-transplant pulmonary metastasis was established with a primary cohort of 308 HCC patients who received liver transplantation between 2007 and 2011 at Ren Ji Hospital. The C-indexes for predicting pulmonary metastasis was 0.85. The calibration curves fitted well between the predicted and actual outcomes. The decision curve analysis indicated that our nomogram was the optimal decision-making strategy for PM prediction compared to Milan, University of California San Franscisco, and up-to-seven criteria. These results were further validated by data from 103 patients who underwent liver transplantation between 2011 and 2012 at the same institution. In conclusion, our nomogram could be used as an effective tool to predict PM after liver transplantation.

Analysis of 9 cases of pediatric-type follicular lymphoma / 中华儿科杂志

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.

Self-assembly of ternary hollow microspheres with strong wideband microwave absorption and controllable microwave absorption properties.

In this study, we report a simple and efficient two-step method consisting of water-in-oil (W/O) emulsion technique and subsequent annealing process for synthesizing the hollow reduced graphene oxide microspheres embedded with Co nanoparticles (Air@rGO€Co). The microspheres showed good electromagnetic properties because of the coexistence of magnetic loss and dielectric loss to microwaves. The minimum reflection loss (RLmin) value of S1.5 reaches -68.1 dB at 13.8 GHz with a thickness of 2.2 mm, and the absorption bandwidth (lower than -10 dB) is 7.1 GHz covering from 10.9 GHz to 18.0 GHz. More interestingly, we can easily controll the microwave absorbing properties of the microspheres by changing the ratio of the two components in the composites. The excellent electromagnetic match at the corresponding resonance peaks for dielectric and magnetic loss play an important role in improving microwave absorption property. Our study provides a good potential method for preparation of lightweight microwave absorbing materials.

Effect of Age on the Time of Neutropenia after Initial Induction Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of age on the time of neutropenia after initial induction therapy for newly diagnosed acute myeloid leukemia (AML) patients.@*METHODS@#Data of 18-65 years old AML patients treated in our hospital from Junuary 2015 to July 2020 were retrospectively analyzed. The clinical characteristics, time of neutropenia after initial induction treatment, early responses, and related influencing factors for the time of neutropenia were analyzed and compared between 18-40 years old group and 41-65 years old group.@*RESULTS@#There were 112 patients enrolled in this study, including 66 (58.9%) males, and their median age was 46 years old. Compared with 18-40 years old group, the incidence of FLT3-ITD gene mutation increased (P=0.039) but core binding factor (CBF) decreased (P=0.003) significantly in 41-65 years old group. The incidence of neutropenia was 97.3%, and the average time was (18.70±1.192) days. The time of neutropenia was (21.43±1.736) days in 41-65 years old group, which was longer than (14.91±1.356) days in 18-40 years old group (P=0.006). The time of neutropenia in CBF positive group was shorter than that in negative group (P=0.012), as well as in patients with remission (CR+CRi) (≤ 2 courses) than those with non-remission (NR) (P=0.024), while in high-risk group was longer than that in low-risk group (P=0.040). Multivariate analysis showed that age, FLT3-ITD gene mutation positive, and non-remission (NR) after two courses of treatment were independent risk factors for the time of neutropenia.@*CONCLUSION@#In non-elderly patients with newly diagnosed AML, age is an influencing factor for the time of neutropenia. Key words　　;

Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: A review.

Liver transplantation (LT) has been accepted as an effective therapy for hepatocellular carcinoma (HCC). The Milan criteria (MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alpha-fetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.

PX-12 Promoting Apoptosis of Multiple Myeloma Cell Line H929 Induced by Bortezomib / 中国实验血液学杂志

OBJECTIVE@#To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib.@*METHODS@#MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H@*RESULTS@#MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G@*CONCLUSION@#PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.

CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML).@*METHODS@#Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M@*RESULTS@#Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M@*CONCLUSION@#The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).@*METHODS@#Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.@*RESULTS@#The ratio of CD4@*CONCLUSION@#The ITI regimen can raise the ratio of CD4

[Application of FTIR spectroscopy to the analysis of eleven kinds of Dendrobium].

OBJECTIVE: To establish an FTIR method for the analysis of Dendrobium. METHOD: Using fourier transform infrared spectrometer to record the characteristic spectra of eleven samples of Dendrobium, and to compare the spectra by PCA (principal component analysis). RESULT: The FTIR spectra of the upper part of the stem displayed significant differences between fresh and dried samples of Dendrobium. On the other hand, differences were observed in the spectra of the middle and lower parts of stems of D. guangxieuse when compared to other species. CONCLUSION: The method of applying PCA to FTIR analysis is a rapid and dependable method for comparing samples of Dendrobium.

A review of life quality in living donors after liver transplantation.

Living-donor liver transplantation (LDLT) has increasingly performed all around the world. However, LDLT donors achieve no medical benefits and are exposed to the risk of complications, and even death. The potential effects of LDLT on donor safety, donor recovery, and post-donation psychological impairment are essential to be better understood. We searched the MEDLINE database to identify articles about the quality of life (QOL) in adults after LDLT donation. Twenty-eight studies with a total of 1944 donors were included in the review. 14 of the 28 studies (50%) had a cross-sectional design, and the remaining half had a prospective design. The Physical Component Score (PCS) decreased immediately after the donation, then returned to the baseline within 6 to 12 months while the Mental Component Score (MCS) remains comparable to that of normative population throughout the procedure. Compared with the left graft (LG) donors, right graft (RG) donors were significantly older, had longer hospital stays and higher rates of postoperative complications, and a higher recipient mortality rate, while there were no difference in the PCS and MCS between the two groups. Our review clearly indicates that the LDLT donors can endure the donation procedure and return to their normal daily life without major problem in the short term. However, to improve the donor selection criteria and ensure the QOL in donors throughout donation procedure, more studies with longer follow up and larger samples are essential and predictors of poor QOL should be identified in study with sufficient response rate and ideal control groups.

Autophagy in tumorigenesis and cancer treatment.

Autophagy is a self-digestion process, wrapping cytoplasmic proteins or organelles to form vesicles for degradation in lysosomes. The process plays an important role in the maintenance of intracellular homostasis. Here we overview articles on autophagy and cancer/tumors in Pubmed and found 327 articles. Autophagy exists in many tumors and is involved in cell malignant transformation and tumor cell growth. In early phases of tumorigenesis, autophagy clears the abnormally folded proteins and dysfunctional organelles such as mitochondria. Autophagy can also inhibit cell stress responses and prevent genetic damage. When a tumor develops, autophagy helps tumor cells survive nutritional deficiencies and hypoxic conditions. Studies of autophagy in the occurrence and progression of tumors should provide new therapeutic strategies for tumors.

Clinical Analysis of Gene Mutation in Adult Patients with B-ALL and Its Influence on Clinical Prognosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the gene mutation in adult patients with B-ALL and its influence on clinical prognosis.@*METHODS@#Clinical data of 226 adult patients with B-ALL were retrospectively analyzed in the period from August 2011 to February 2018. The incidence of gene mutation in all patients were detected, and the influence of mutation gene on clinical prognosis were estimated. Cox regression model were used to evaluate the independent prognostic factors.@*RESULTS@#208 (92.04%) of 226 patients showed gene mutations, and the median mutation number was 2 (0-8). Among them, 54 cases (23.89%) showed 14 or more mutations. The top five mutation types of all patients were SF1, FAT1, MPL, PTPNII and N-RAS respectively. The median OS and median RFS times of 226 patients were 27.0 (5.5-84.0) months and 22.5 (0-81.0) months respectively. The OS and RFS times of Ph@*CONCLUSION@#Gene mutations are common in all adult B-ALL patients, and the clinical prognosis of patients with JAK and epigenetics-related signaling pathway mutations is worsen, while the WBC level closely relates to the clinical prognosis of the patients.

Safety and efficacy of patients with refractory B-lymphoblastic leukemia treated with anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy and side effects of anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) regimen for refractory B-lymphoblastic leukemia. Methods: 10 patients with refractory B-lymphoblastic leukemia with minimal residual disease (MRD) negative after anti-CD19 CAR-T cell treatment, then bridging to allo-HSCT from November 2017 to March 2019 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Results: ①Among 10 patients, 5 were males and 5 females, with a median age of 23.6 (10-31) years. 9 patients were diagnosed refractory acute lymphoblastic leukemia and the other one was chronic lymphoblastic leukemia. 10 patients reached MRD negative 30 days after anti-CD19 CAR-T cell. ②The donors were identical sibling (2 cases) and haploidentical family member (8 cases) . The median time from MRD negative after CAR-T treatment to transplantation were 32.5 (20-60) days. ③10 patients obtained complete haploidentical engraftment. The median time of neutrophil implantation was 15 (15-21) days, and 19 (17-30) days of platelet implantation. ④ After conditioning, no hepatic venoocclusive disease and hemorrhagic cystitis occurred. One patient had leakage syndrome and got improved after intervention such as limited water entry, albumin supplementation and diuresis. 8 (80%) patients had fever, 2 cases experienced acute graft-versus-host disease (GVHD) grade Ⅱ, 1 case with aGVHD grade Ⅲ. Among 9 survivals, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 262 (150-540) days and the estimated 1-years overall survivaln (OS) and disease free survival (DFS) were (90.0±1.0) % and (85.7±1.3) %, respectively. Conclusion: Anti-CD19 CAR-T cell bridging to allo-HSCT regimen is a feasible choice with favorable outcome for refractory B-lymphoblastic leukemia.

Effect of nilotinib on pregnancy outcome in female patients with chronic myeloid leukemia / 中华血液学杂志

Objective: To observe the pregnancy outcome among patients with chronic myeloid leukemia (CML) treated with Nilotinib (NIL) . Methods: Clinical data of pregnancy delivery in CML patients treated with NIL from March 2015 to January 2019 were retrospectively collected. Results: A total of 11 patients were recruited with median pregnancy age 28 (25-40) years. The median duration of NIL treatment before pregnancy was 34 (3-48) months. There were 12 pregnancies, included 2 planned ones and 10 (83.3%) unplanned. In the 10 unplanned patients, 9 (90.0%) received NIL 600 mg/d. The median exposure time were 4 (4-7) weeks. In eight patients with delivery outcomes, 5 cases had well-developed babies, 2 had spontaneous abortion and 1 case with an baby of syndactyly deformity, whose mother was exposed to NIL 600 mg/d for 7 weeks in the early trimester of pregnancy. Seven infants were 4 boys and 3 girls with the median height at birth 50 (41-54) cm and median weight 3.2 (3.0-4.6) kg. They all grew with a normal pattern and well developed. Now the median age is 19 (4-41) months. The disease status during 12 pregnancies included 3 cases in CMR, 2 cases in MR(4.0), 3 cases in MMR, 4 cases not acquiring MMR. The median time of drug discontinuation was 35 (15-36) weeks during pregnancy. No patient lost CHR during this period. Conclusions: Female CML patients exposed to NIL 600 mg/d for 4 weeks in early pregnancy can give birth to normal babies, but there is still a risk of spontaneous abortion and congenital malformations.