Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study / 中华预防医学杂志

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.

Application progress of radiolabeled drugs in new drug research and development in China / 药学学报

The metabolism study of radiolabeled drugs plays an important role in the development of new drugs. It provides information on drug absorption, metabolism, tissue distribution and excretion, and plays an irreplaceable role in the metabolite safety evaluation and mass balance of new drugs. The new guidance draft on clinical trials of radiolabeled drugs recently released by the US FDA puts forward higher standards and has been widely concerned by the industry. In recent years, in the research and development of new drugs in China, 14C labeled drugs have been used to carry out clinical metabolism studies, which has overcome key technical bottlenecks and accumulated experience. This paper summarizes the above research progress, analyzes the existing problems, and preliminarily looks forward to the future technological development and application.

Analysis of metabolites of rocuronium bromide in human bile and the study of transmembrane transport mechanism / 药学学报

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).

Establishment of Cytarabine-resistant Acute Lymphoblastic Leukemia Cell Lines and Its Resistance Mechanism / 中国实验血液学杂志

OBJECTIVE@#To establish cytarabine-resistant acute lymphoblastic leukemia (ALL) cell lines and investigate its possible resistant mechanism.@*METHODS@#Low-concentration cytarabine (Ara-C) continuously induced and cultured Jurkat and Nalm-6 cells to construct cytarabine-resistant cell lines Jurkat/Ara-C and Nalm-6/Ara-C. The cell viability was detected by CCK-8 assay, and the distribution of cell cycle was detected by flow cytometry. Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of multidrug resistant gene and Ara-C metabolic enzymes. The expression levels of cyclin were detected by Western blot.@*RESULTS@#Jurkat/Ara-C and Nalm-6/Ara-C drug-resistant cell lines were successfully established, the resistance index of which was 1 973.908±161.163 and 7 231.643± 1 190.624, respectively. Drug-resistant cell lines had no cross-resistance to commonly used chemotherapeutic drugs, such as doxorubicin. Flow cytometry showed that the ratio of G@*CONCLUSION@#Cytarabine-resistant ALL cell lines are successfully established by using low concentration continuous induction method, and its drug-resistant mechanism may be related to the deficiencies of DCK and cyclinB1.

A physiologically-based pharmacokinetic model adequately predicted the human pharmacokinetic profiles of ZSP1601, a novel pan-phosphodiesterase inhibitor / 药学学报

ZSP1601, a novel pan-phosphodiesterase inhibitor is in development for the treatment of nonalcoholic steatohepatitis. A physiologically-based pharmacokinetic (PBPK) model was developed to predict the pharmacokinetics of ZSP1601 in human. The PBPK model following intravenous and oral dose of ZSP1601 in rats and dogs was firstly built using preclinical in vitro and in vivo data. The PBPK model in human was then built based on models in animal. The in vitro-in vivo extrapolation (IVIVE) method and some allometric scaling methods were used to predict the clearance in human, respectively. The PBPK models using IVIVE and allometry of unbound CL plus the rule of exponents methods predicted the pharmacokinetics of ZSP1601 in healthy Chinese subjects successfully. The predicted parameters Cmax and AUC following single oral dose administration were within 0.5-2 folds of the observed data. The model was optimized and the final model was used to predict the pharmacokinetics of ZSP1601 in North European Caucasian, Geriatrics, Obese and Morbidly Obese, respectively. Animal studies were approved by the Animal Management and Use Committee of Suzhou AppTec Inc., and the approved No. is SZ20140916.

Relationship between the living environment and respiratory diseases in primary school students in Taizhou City / 上海预防医学

Objective:To understand the relationship between the living environment and respiratory diseases in primary school students in Taizhou City of Zhejiang Province， and to explore the related factors. Methods:From 2018 to 2019， a total of 1 044 students from grade 2 to grade 5 of a primary school in Taizhou were selected by cluster random sampling method for two consecutive years to conduct a questionnaire survey during November 15 to December 31. Correlation between living environment and respiratory diseases in primary school students was analyzed. Results:Among the 1 044 students completed valid questionnaires， 224 students had suffered from respiratory diseases in the past year， accounting for 21.5% from 2018 to 2019. Logistic regression analysis showed that existence of waste collection site within 100 m of household （OR=2.522， 95%CI：1.105-5.752）， family passive smoking exposure （OR=1.781， 95%CI： 1.234-2.571）， and household use of air pollution chemicals （OR=1.915， 95%CI：1.396-2.627） were independent risk factors for respiratory diseases in primary school students. Conclusion:There are some risk factors of respiratory diseases in the living environment of primary school students in Taizhou， and prevention should be carried out in daily life to reduce the prevalence of respiratory diseases among primary school students.

Pharmacokinetics of FGF21-164 fusion protein in mice using UHPLC-MS/MS method / 药学学报

FGF21-164 is a fusion protein obtained by structural modification and coupling of endogenous FGF21. It is a candidate drug used in the treatment of glucose and lipid metabolic disorders caused by obesity. In this study, the candidate peptide mass spectrometry information of the protein hydrolyzed by trypsin was predicted by Skyline software and verified by high resolution mass spectrometry. The specific surrogate peptide (YLYTDDAQQTEAHLEIR) with the best mass response was selected after optimizing ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Under ESI positive ion mode, the parent ion m/z 689.3 with 3 charge and the product ion m/z 738.4 with single charge can be monitored. After dilution by PBS, the serum samples were denatured under 60 ℃ and alkylated to reduce the matrix effect, then incubated with trypsin at 37 ℃ for 2 h, to obtain the surrogate peptide. The chromatographic separation was carried out on an EclipsePlus C18 column (2.1 mm×50 mm, 1.8 μm) using aqueous solution containing 0.1% formic acid (phase A) and acetonitrile solution containing 0.1% formic acid (phase B). Finally, the concentration of FGF21-164 fusion protein in mouse serum was quantitatively analyzed by external standard method by monitoring the above ion pairs using triple quadrupole mass spectrometer. This method showed a good linearity in the range of 2.50-500 μg·mL-1 (r = 0.998 8), and was successfully applied to the pharmacokinetic study of FGF21-164 fusion protein in mice. This experiment was approved by the Experimental Animal Ethics Committee of Shanghai Institute of Materia Medica, Chinese Academy of Sciences (batch number: 20180004040450). Compared with the endogenous FGF21, the t1/2 of FGF21-164 fusion protein was prolonged from 0.5 h to 2.6 h, which is expected to prolong the therapeutic efficacy of this protein.

Advances in bioanalysis of antibody drugs by LC-MS / 药学学报

Liquid chromatography-tandem mass spectrometry (LC-MS) is a promising alternative or complementary method for traditional ligand-binding assays (LBA) in antibody drug bioanalysis. However, issues related to method development, sample preparation, sensitivity and quantitative accuracy need to be addressed. This paper reviews progress in bioanalysis of antibody drugs by LC-MS methods, introduces the principle of the LC-MS method for the analysis of antibody drugs, and describes the challenges faced in quantitative antibody analysis by the LC-MS method. New strategies that can be used to deal with these challenges include: selection of surrogate peptides, purification and enrichment of samples, improvement in enzymatic digest efficiency, enrichment of peptides, and use of low rate LC. We review the application of LC-MS technology in the biological analysis of antibody drugs and discuss the prospect of using the LC-MS method for the analysis of antibody drugs.

Effects of estimated glomerular filtration rate on all-cause mortality in the elderly aged 65 years and older in 8 longevity areas in China / 中华流行病学杂志

To investigate the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in the elderly aged 65 years and older in longevity areas in China. Data used in this study were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey, 1 802 elderly adults were collected in the study during 2012-2017/2018. In this study, the elderly were classified into 4 groups, moderate-to-severe group [<45 ml·min(-1)·(1.73 m(2))(-1)], mild-to-moderate group [45- ml·min(-1)·(1.73 m(2))(-1)], mild group [60- ml·min(-1)·(1.73 m(2))(-1)] and normal group [≥90 ml·min(-1)·(1.73 m(2))(-1)] according to their eGFR levels. After 6 years of follow-up, 852 participants died, with a mortality rate of 47.3. Multivariate Cox regression analysis showed that the levels of eGFR were negatively correlated with all-cause mortality risk in the elderly (the of elderly was 0.993 and the 95 was 0.989-0.997 for every unit of eGFR increased, =0.001), while compared with the group with normal eGFR, the (95) of the elderly in the moderate-to-severe group, mild-to-moderate group, and mild group were 1.690 (1.224-2.332, =0.001), 1.312 (0.978-1.758, =0.070), 1.349 (1.047-1.737, =0.020) respectively [trend test <0.001]. The decrease in eGFR was associated with higher mortality risk among the elderly in longevity areas in China.

Metabolism and pharmacokinetics of drugs applied for the treatment of Corona Virus Disease 2019 (COVID-19) / 药学学报

Based on Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th edition), the metabolism and pharmacokinetics of drugs used in clinical treatment of COVID-19 were reviewed. The antiviral drugs include remdesivir, chloroquine/hydroxychloroquine, lopinavir/ritonavir, favipiravir, arbidol, baicalin, baicalein and forsythin. Among them, the metabolism and pharmacokinetics of arbidol, baicalin and forsythin are the research results of the author's laboratory. This article aims to provide reference for the efficacy evaluation and rational drug use of COVID-19.

Studies on the metabolism of a triptolide derivative (5R)-5-hydroxytriptolide in vitro / 药学学报

The purpose of current study is to investigate the metabolic profile of a triptolide derivative (5R)-5-hydroxytriptolide in vitro. (5R)-5-Hydroxytriptolide was incubated with the hepatocytes of human, monkey, dog, rat or mouse, respectively. Compared with inactivated hepatocytes, four metabolites were identified in hepatocytes from all five species: oxidative ring-opening metabolite (M1), glutathione-conjugating metabolite (M2), and monooxidative combined with glutathione-conjugating metabolites (M3-1 and M3-2), respectively. In human or rat liver microsomes, seven metabolites of (5R)-5-hydroxytriptolide were found, dehydrogenated metabolite (M4) and monooxidative metabolites (M5-1–M5-6), respectively. Reference standards for the metabolites were obtained either through chemical semisynthesis or biotransformation through rat primary hepatocytes. The structures of five metabolites were confirmed, which were 12,13-epoxy ring-opening metabolite M1, 12-glutathione-conjugating metabolite M2, (16S)-, (2R)- and (19R)-monohydroxylated metabolites M5-1, M5-4, and M5-5, respectively. In vitro activity assay revealed that only (2R)-hydroxylated metabolite exhibited weak immunosuppressive activity with less than one-tenth the activity of its parent drug, and a significant decrease in toxicity was observed. It is suggested that (5R)-5-hydroxytriptolide might undergo metabolic inactivation and detoxification in vivo.

Metabolism and pharmacokinetics of covalent tyrosine kinase inhibitors / 药学学报

Covalent tyrosine kinase inhibitors (TKIs) can inhibit the signaling pathway of tumor cells by covalent binding with cysteine residues of target proteins, which has the advantages of high potency, extended duration of action and overcoming drug resistance. In this article, we will review the metabolism and pharmacokinetics of some covalent TKIs. Currently, the covalent TKIs approved by US food and drug administration (FDA) are afatinib, neratinib, dacomitinib, osimertinib, ibrutinib and acalabrutinib. Pyrotinib have been approved by National Medical Products Administration (NMPA) to reach the market recently. Covalent TKIs can covalently bind with plasma proteins, especially human serum albumin, thus effected the pharmacokinetics of these drugs.

Rapid and simultaneous determination of nifedipine and dehydronifedipine in human plasma / 药学学报

Nifedipine, a calcium channel antagonist, is metabolized mainly by CYP3A4 to dehydronifedipine. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine nifedipine and dehydronifedipine in human plasma using d6-nifedipine/d6-dehydronifedipine as internal standards. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a Hypersil Gold C18 (50 mm×2.1 mm, 1.9 μm). The mobile phase consisted of methanol and 5 mmol·L-1ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 347.3→254.1 for nifedipine, m/z 345.2→283.9 for dehydronifedipine, m/z 353.3→257.1 for d6-nifedipine, m/z 351.2→286.9 for d6-dehydronifedipine. The method had a linear calibration curves over the concentrations of 0.10-80.0 ng·mL-1 for nifedipine and 0.050-40.0 ng·mL-1 for dehydronifedipine. The validated LC-MS/MS method has been successfully used study pharmacokinetic interactions of apatinib (CYP3A4 inhibitor) and nifedipine (CYP3A4 substrate) in human. This clinical trial was approved by the society of ethics and conducted in the first hospital of China medical university.

Comparative study of disposition of scutellarin and its major metabolite with different administration routes in rats / 药学学报

The study was designed to establish an LC-MS/MS method for the simultaneous determination of scutellarin and its major metabolite isoscutellarin in rat tissues and plasma, and to investigate the effect of different route of administration on the tissue distribution of scutellarin and its metabolite in rats. Rats were treated both intravenously and intragastrically with 20 and 80 mg·kg−1 scutellarin, respectively. Blood and tissues were collected at predetermined intervals. The concentrations of scutellarin and isoscutellarin were determined by a validated LC-MS/MS method. The method was linear in concentration ranges of 10.0/5.00 − 5 000/2 500 ng·mL−1 for scutellarin/isoscutellarin in the rat plasma and 30.0/15.0 − 10 000/5 000 ng·g−1 in tissues with acceptable accuracy and precision. Data obtained after an intravenous administration of scutellarin to rats showed that the drug was distributed predominantly into the small intestine, bladder and kidney. The exposures of the metabolite isoscutellarin in plasma and tissue were both less than 5%of the parent drug. After an intragastric administration, stomach wall and small intestine were the preferred sites for scutellarin disposition, followed by bladder, adrenal gland and lung at concentrations significantly higher than its plasma concentration. The plasma exposure of isoscutellarin was higher than that of the parent drug, but its tissue exposure was significantly lower than that of scutellarin. The method established in this study was successfully applied to characterization of the tissue profiles of scutellarin and its metabolite in rats. The route of administration has a marked impact on the disposition of scutellarin and its metabolite in rats. Ratios of the tissue to plasma concentrations after intragastric administration were obviously higher than those after intravenous administration. Scutellarin could pass the blood-brain barrier in a marked extent, but isoscutellarin was not detected in the rat brain, which may be attributed to the fact that scutellarin is a higher-affinity substrate for OATP than isoscutellarin.

Simultaneous determination of flavonol glycoside and its major metabolites by LC-MS/MS in rat plasma / 药学学报

Flavonol glycoside is in clinical trials for treatment of hyperlipidemia. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of flavonol glycoside (M0), aglycone (M1) and glucuronide conjugate (M2) in rat plasma. d6-Flavonol glycoside was used as internal standard (IS). After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a XDB C18 column (50 mm×4.6 mm, 1.8 μm) using a gradient elution procedure. The mobile phase consisted of methanol and water (0.2% formic acid) at a flow rate of 0.6 mL·min−1. The total run time was 4.5 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 461.3 → m/z 299.1 for M0, m/z 299.1 → m/z 283.1 for M1, m/z 475.0 → m/z 299.1 for M2, and m/z 467.3 → m/z 305.1 for d6-flavonol glycoside. The method was validated and successfully applied to the pharmacokinetics study of flavonol glycoside in SD rats which were given flavonol glycoside (30 mg·kg−1) by gavage. The Cmaxof M0 is (341 ±106) ng·mL−1 and AUC0−t is (1 960 ±725) h·ng·mL−1, while the Cmaxof M2 is (1 720 ±843) ng·mL−1and AUC0−t is (8 510 ±2 920) h·ng·mL−1. The results suggest that flavonol glycoside existed mainly in the form of M0 and M2 in rats. After flavonol glycoside being hydrolyzed by the intestinal flora, it was absorbed in the form of aglycone and further metabo­lized to M2 after the first-pass effect. In this paper, the main metabolites of flavonol glycoside in rat plasma were determined for the first time, which provided a basis for the design of clinical pharmacokinetic experiment.

Role of human liver and intestine esterases in drug design and development / 药学学报

Human carboxylesterase (CES) and arylacetamide deacetylase (AADAC) are important numbers of the serine esterase superfamily. They are involved in hydrolytic procedure of human endogenous cholesteryl esters, as well as drug metabolism, activation and detoxication. They are closely related to the personalized medication of drugs, especially for prodrugs. This review summarizes their structure and distribution, metabolic characteristics and research progress in recent years, which will provide a reference for new drug development and rational drug design.

Simultaneous determination of fosaprepitant and its metabolite aprepitant in human plasma by liquid chromatography-tandem mass spectrometry / 药学学报

An LC-MS/MS method was developed for the simultaneous determination of fosaprepitant and aprepitant in human plasma, and applied to a pharmacokinetic study of 150 mg fosaprepitant dimeglumine injection to 12 Chinese healthy volunteers. The analytes and internal standards were extracted from plasma by protein precipitation with acetonitrile and separated on a Cortex C18+ (50 mm×2.1 mm, 2.7 μm) column using a gradient elution procedure. Mass spectrometry was performed in negative MRM mode, and parent-to-produce transitions were as follows:m/z 613.1→78.9 for fosaprepitant, m/z 617.0→78.9 for d4-fosaprepitant, m/z 533.2→275.1 for aprepitant and m/z 537.2→279.1 for d4-aprepitant. Plasma sample was basified to stabilize fosaprepitant. The standard curves were demonstrated to be liner in the range of 15.0 to 6 000 ng·mL-1 for fosaprepitant and 10.0 to 4 000 ng·mL-1 for aprepitant. The intra-day precisions and inter-day precisions and accuracy were within the acceptable limits for all concentrations.

Protective effects of C/EBPα on podocytes in diabetic nephropathy / 中华肾脏病杂志

Objective To explore the effects of C/EBPα knockout in podocyte on diabetic nephropathy and its mechanisms.Methods C/EBPαloxp/loxp mice were crossed with podocin-cre mice to obtain F1 hybrids and then propagated until homozygous mice (C/EBPαf/f) were obtained.Diabetic nephropathy (DN) models were established by low-dose streptozotocin (STZ,100 mg/kg) administration after 25 weeks of normal diet or 45％ high-fat diet treatment,and biochemical indicators of blood and urea were measured.The morphological characteristics and the proteins regulating oxidative stress and mitochondrial function were detected.Results The type 2 DN models were successfully constructed based on transgenic mice.The kidneys of 8-month-old C/EBPαf/f mice did not show obvious morphological changes,but after constructing DN models,they showed obvious renal impairment,inflammation and oxidative stress.Compared with wild-type DN mice,the protein levels of nephrin and E-cadherin in DN C/EBPαf/f mice with DN were significantly decreased (P ＜ 0.01);fibronectin and Nrf2 protein levels were all increased (all P ＜ 0.05).Keap1,phospho-AMPK and mitochondrial function related genes Pgc-1α protein levels were all decreased (all P ＜ 0.05).Conclusion Podocyte C/EBPα knockout exacerbates diabetic nephropathy by promoting fibrosis and inhibiting Pgc-1α-mediated mitochondrial antioxidant function.

Influence of Wenxin granule combined propranolol on related hormone levels and cardiac function in patients with hyperthyroidism and atrial fibrillation / 心血管康复医学杂志

Objective : To observe influence of Wenxin granule combined propranolol on related hormone levels and cardiac function in patients with hyperthyroidism and atrial fibrillation (AF).Methods :A total of 136 AF patients with hyperthyroidism diagnosed in our hospital were randomly and equally divided into propranolol group and com-bined treatment group (received propranolol combined Wenxin granule ).Both groups received routine treatment for eight weeks also .Serum levels of free triiodothyronine (FT3) ,free thyroxine (FT4) and thyrotropic-stimulating hormone (TSH) ,blood pressure :SBP 、 DBP ,HR and LVEF before and after treatment were compared between two groups.Results :Compared with before treatment ,there were significant reductions in serum levels of FT 3 and FT4 ,SBP ,DBP and HR ,and significant rise in serum TSH level and LVEF after treatment ,in two groups , P＜0.05 or ＜0.01. Compared with propranolol group after treatment ,there were significant reductions in serum levels of FT3 [ (6.68 ± 1.94) pmol/L vs.(4.39 ± 1.34) pmol/L] and FT4 [ (28.67 ± 5.17) pmol/L vs .(22.67 ± 4.86) pmol/L] ,SBP [ (127.79 ± 10.86) mmHg vs.(121.76 ± 9.43) mmHg] ,DBP [ (81.65 ± 8.41) mmHg vs.(75.12 ±8.16) mmHg] and HR [ (85.67 ± 7.64) beats/min vs .(80.79 ± 6.47) beats/min] ,and significant rise in serum TSH level [ (1.28 ± 0.26) mU/L vs.(1.81 ± 0.34) mU/L] and LVEF [ (56.28 ± 5.12)% vs.(59.76 ± 4.25)%] in combined treatment group ,P＜0.05 or ＜0.01. Total effective rate of combined treatment group was significant-ly higher than that of propranolol group (95.59% vs.82.35%,P＝0.014).There was no significant difference in incidence of adverse reactions between two groups , P＝1.000 .Conclusion :Wenxin granule combined propranolol can significantly improve thyroid hormone levels and cardiac function in patients with hyperthyroidism ,which is worth extending .

Comparison of different styles of allogeneic hematopoietic stem cell transplantation as first-line treatment treated with severe aplastic anemia in children and adolescents / 中华血液学杂志

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.