Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

Objective:To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse ( HR=3.91, 95% CI 1.96-7.79; HR=4.15, 95% CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse ( HR=6.50, 95% CI 2.58-16.34; HR=5.19, 95% CI 1.78-15.16), with ETV6::RUNX1 ( HR=0.23, 95% CI 0.07-0.74) and HSCT after relapse ( HR=0.24, 95% CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions:Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

Objective:To analyze the nutritional status of elderly inpatients using Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:A total of 5 236 elderly patients (aged 65 years or older) who were hospitalized at the West China Hospital, Sichuan University from March 2021 to March 2022 were included. The nutritional status was analyzed using the GLIM diagnostic criteria for malnutrition.Results:The rate of patients at nutritional risk was 30.29%, and the incidence of malnutrition as per GLIM criteria was 15.64%. The levels of hemoglobin, albumin, triglycerides, and cholesterol, and body mass index of the malnutrition group were lower compared with the non-malnutrition group, and the differences were statistically significant ( P<0.05). The non-malnutrition group had significantly shorter hospital stay and lower hospitalization costs compared with the malnutrition group ( P<0.001). Conclusions:The GLIM criteria is suitable for evaluating the nutritional status in elderly inpatients. The incidence of malnutrition in elderly inpatients is relatively high, which deserves attention in clinical management.

Objective:To analyze the relationship between FAB morphological classification and World Health Organization (WHO) 2016 classification in children with acute erythroid leukemia(AEL), and to summarize the clinical features and prognosis.Methods:Clinical data of de nova childhood AEL patients from January 1, 2002 to December 31, 2019, in Pediatric Blood Disease Center, Institute of Hematology & Blood Disease Hospital were retrospectively analyzed.All of them were re-evaluated according to the WHO 2016 classification.Results:(1) A total of 20 patients were diagnosed as AEL by FAB classification.According to the criteria of WHO 2016, they were re-diagnosed as myelodysplastic syndromes (MDS)- refractory anemia with excess of blasts (11 cases), acute myeloid leukemia with MDS-related changes (3 cases), acute monocytic leukemia (1 case), and pure red leukemia (PEL, 5 cases). (2) Pathological hematopoiesis was frequently detected in bone marrow smears.Auer bodies were seen occasionally in some blasts.The most common antigen expressing were CD 117, CD 13, CD 33, CD 34, CD7, and CD 38.Karyotype analysis was performed in 18 cases successfully, involving 6 cases with abnormal karyotypes, including + 8, -7, 22p+ , t (3; 5: ? ), + 3q-, 15q-, and del (9)(q13). (3) Thirteen cases were treated by chemotherapy, and the one-course complete remission rate was 38.5%.By July 1, 2020, only 2 cases were alive without disease.The overall survival was 49 months and 11 months, respectively. Conclusions:Childhood AEL is susceptible to pathological hematopoiesis, poor response to early chemotherapy and poor prognosis.After re-evaluation according to WHO 2016 classification, most of them were diagnosed as MDS-related.Therefore, adjusting the suitable induction regimen with allogeneic hematopoietic stem cell transplantation may improve the prognosis.

Objective:To explore the clinical application of NanoString fluorescent barcode technology in the molecular subtyping of diffuse large B-cell lymphoma (DLBCL), and to analyze the correlation between the cell-of-origin subtype and prognosis of patients.Methods:The tumor tissue samples of 12 patients with DLBCL at the Third People's Hospital of Datong of Shanxi Province and 8 patients with DLBCL at Peking University, Health Science Center between January 2014 and December 2019 were collected. According to Hans algorithm, all patients were divided into 1 case of germinal center-derived B-cell (GCB) type and 19 cases of non-GCB type. NanoString platform was used to analyze the expression level differences of 15 genes-related to Lymph2Cx molecular subtyping of all samples at mRNA level. Hierarchical clustering was used to subgroup 20 DLBCL cases and to contrast the prognosis in different subgroups according to the subtyping.Results:NanoString fluorescent barcode technology was used to detect samples of 20 DLBCL cases and hierarchical clustering analysis was performed, and then subtyping results showed that 11 cases were GCB-like type and 9 cases were activated B cell (ABC)-like type. Based on Hans algorithm, 10 GCB-like cases were non-GCB type. According to the survival analysis, GCB-like group had a better overall survival compared with that in ABC-like group ( P=0.019). Conclusion:NanoString fluorescent barcode technology can be successfully applied to the cell-of-origin subtyping of DLBCL, and the molecular subtyping strategy can effectively predict the prognosis of patients.

Objective:To explore the relationship between sleep duration and depressive symptoms in middle-aged and elderly people.Methods:A total of 11 931 middle-aged and elderly people aged ≥55 years who participated in the baseline survey of the "Community Cohort Study of Specialized Nervous System Diseases" in China from 2018 to 2019 were selected to obtain basic information about their lifestyle, food intake frequency, disease history, sleep duration. The body height and weight were measured, and body mass index (BMI) were calculated. The subjects with depressive symptoms were screened with the Geriatric Depression Scale (GDS-30). Restricted cubic spline model and multivariate logistic regression model were used to analyze the relationship between sleep duration and depressive symptoms.Results:Among the middle-aged and elderly people aged ≥55 years, 17.79% reported sleep duration less than 7 hours, 16.84% reported that their sleep duration ≥9 hours, and the detection rate of depression symptoms was 7.95%. After adjusting for factors such as region, age, gender, the restricted cubic spline results showed the U-shaped relationship between sleep duration and the risk for depressive symptoms, the results of multivariate logistic regression analysis showed that the risk for depressive symptom in middle-aged and elderly people aged ≥55 years with sleep duration ≤5 hours, 6 hours, and ≥9 hours were 1.749(95% CI:1.279-2.392), 1.284(95% CI:1.021-1.615) and 1.260(95% CI:1.033-1.538) times higher compared with the counterparts with sleep duration 7-8 hours, the risk for depressive symptom in women with sleep duration ≤5 hours, 6 hours and ≥9 hours were 2.115 (95% CI:1.473-3.038), 1.605(95% CI:1.213-2.123) and 1.313(95% CI:1.011-1.705) times higher, respectively, compared with counterparts with sleep duration 7-8 hours, the risk for depressive symptoms in 55-64-year-old middle-aged and elderly people with sleep duration ≤5 hours and ≥9 hours were 1.806 (95% CI:1.014-3.217) and 1.478 (95% CI:1.060-2.061) times higher compared with counterparts with sleep duration 7-8 hours, and the risk for depressive symptoms in elderly people aged 65-74 years with sleep duration ≤5 hours was 2.112 (95% CI:1.327-3.361)times higher compared with counterparts with sleep duration 7-8 hours, the differences were all significant ( P<0.05). There was no statistically significant association between sleep duration and depressive symptoms in men and in elderly people aged ≥75 years ( P>0.05). Conclusion:Insufficient or prolonged sleep was independently associated with depressive symptoms in middle-aged and elderly people, showing a U-shaped relationship, especially in women and in middle-aged and elderly people aged 55-64 years.

Objective:To explore the clinical features of bloodstream infections (BSI) in children with acute myeloid leukemia (AML) during the first induction chemotherapy.Methods:The clinical data, pathogen of BSI, antibiotic susceptibility in vitro, complications and prognosis of 204 newly diagnosed AML children admitted to Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2009 to December 2015 were analyzed retrospectively. χ 2 test was used for the comparison between groups and Logistic regression was used for BSI risk factor analysis. Results:Among 204 patients, 116 were males and 88 were females. The age was 8 (ranged from 1 to 14) years. Among them, 170 patients received MAE chemotherapies (etoposide, mitoxantrone and cytarabine) and 25 received IAE chemotherapies (etoposide, idarubicin and cytarabine). The other 9 patients used granulocyte colony stimulating factor (G-CSF)-priming regimen (aclacinomycin or homoharringtonine, cytarabine and G-CSF) for induction treatments. A total of 28 patients experienced BSI and the incidence rate was 13.7% (28/204), 26 of them developed BSI once and 2 patients developed twice. Gram-positive bacteria were predominant pathogens accounting for 53.3% (16/30) while gram-negative bacteria accounting for 40.0% (12/30) and fungal accounted for 6.7% (2/30). The most common detected pathogens were Coagulase negative Staphylococcus (CoNS, 26.7% (8/30)), followed by Streptococcus spp. (13.3% (4/30)) and Escherichia coli (13.3% (4/30)). Among Gram-negative bacteria (GNB), 3 cases showed carbapenem resistance and 2 cases were Stenotrophomonas maltophilia. BSI-related mortality was 28.6% (8/28). Infections caused by drug-resistant GNB or fungi resulted in 6 fatal cases. The incidence rate of BSI in group with severe neutropenia was higher than in group without it (16.6% (25/151) vs. 5.7% (3/53), χ2=3.933, P=0.047). Multivariable analysis showed severe neutropenia at the onset of fever was independent risk factor of BSI ( OR=4.258,95% CI 1.097-16.524, P=0.036). Conclusions:During the first induction chemotherapy courses, Gram-positive bacteria cause most of the BSI. Drug-resistant bacteria related infection often result in fatal outcomes. Severe neutropenia is a significant risk factor.

Objective:To explore the laboratory characteristics and diagnostic methods for therapy-related acute megakaryocytic leukemia (t-AMKL).Methods:The data of one child with acute lymphoblastic leukemia (ALL) in the Blood Disease Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College in September 2014 was retrospectively analyzed. After inducing remission for more than 43 months, the child was diagnosed as t-AMKL.Results:After the diagnosis of ALL, the child was given chemotherapy with standard childhood ALL regimen. After 43 months, t-AMKL was diagnosed by comprehensive morphology, cytogenetics, and molecular biology. Bone marrow morphology showed that the proportion of primitive cells was 0.44; flow cytometry showed the phenotype was abnormal myeloid primitive cells; the pathology result showed that the abnormal cells weakly expressed CD42b and CD61; the electron microscopy showed platelet peroxidase (PPO)-positive and myeloperoxidase (MPO)-negative; the bone marrow immunohistochemistry showed the positive rate of CD41 was 34%; the child had a complex karyotype. After reviewing his medical history, he was diagnosed as t-AMKL.Conclusion:The t-AMKL is relatively rare, and it is helpful to improve the prognosis of patients by completing the relevant examinations for early diagnosis.

Objective:To analyze the clinical characteristics and prognosis of mixed phenotype acute leukemia (MPAL) in children.Methods:The data of 29 children diagnosed as MPAL in the Pediatric Blood Disease Center, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences from January 1, 2005 to December 1, 2019 were collected retrospectively. The morphology, immunophenotypes, cytogenetics, molecular biological characteristics, induction chemotherapy regimen, and prognosis were analyzed. Kaplan-Meier Method was used to draw survival curve. Log-Rank was used for univariate analysis.Results:(1) Among 29 MPAL cases, there were 1 case with KMT2A rearrangement, 1 case with BCR-ABL1, 13 cases with B/myeloid(B-M) type, 12 cases with T/myeloid(T-M) type and 2 cases with acute undifferentiated leukemia. (2) The common immunophenotypes were CD33 (23 cases, 79%), CD34 (25 cases, 86%) and HLA-DR (20 cases, 69%), and CD19 was positive in 17 cases (59%). (3) In molecular genetics analysis, 8 cases were detected to have abnormal gene fusion, including 1 case with MLL-AF4 fusion gene, 1 case with BCR-ABL1 fusion gene, 3 cases with TEL-AML1 fusion gene, 2 cases with WT1 and 1 case with FLT3-ITD. (4) In cytogenetics analysis, 27 cases obtained chromosome karyotypes, including 14 cases with abnormal karyotypes and 10 cases were complex karyotypes. (5) In treatment efficacy analysis, 27 cases received induction chemotherapy and the complete remission(CR) rate was 85%（23/27）.The 5-year disease free survival(DFS) rate was (71±10)% and 5-year overall survival(OS) rate was (74±10)%. Thirteen of 14 cases received acute lymphoblastic leukemia（ALL） induction therapy achieved CR, while 10 of 12 cases received hybrid induction therapy achieved CR. No significant difference was found in 5 year-OS rates between cases with ALL induction therapy and hybrid induction therapy ((77±15)% vs. (80±13)%, χ2=0.027， P=0.870). Conclusions:MPAL is a rare childhood leukemia and is prone to incorporate complex karyotypes. Induction therapy with ALL or hybrid regimens is a good choice to obtain favorable prognosis.

Objective:To evaluate the predictive role of ETV6-RUNX1 fusion gene in protocol CCLG-ALL-2008 as well as identify the prognostic factors that influence the outcome of ALL with ETV6-RUNX1 fusion gene.Methods:One hundred and seventy-eight patients newly diagnosed with pediatric acute lymphoblastic leukemia with ETV6-RUNX1 rearrangement from April 2008 to April 2015 were enrolled in CCLG-ALL-2008. The follow up period ended in July 2018; we performed retrospective analyses of their data to determine the efficacy of the regimen and the prognostic factors.Results:The median age of the study population (178 pediatric patients) , including 100 boys and 78 girls was 4 (1-13) y, and the median white blood cell count at diagnosis was 9.46 (1.25-239.83) ×10 9/L. Three patients died, and 1 was lost to follow up by the end of the first induction chemotherapy, resulting in an induced remission rate of 97.8% (174/178) . The cumulative incidence of relapse was 15.9% with a median follow up of 73.5 mon. Total 83.3% of the relapse cases were those of isolated bone marrow relapse, while 79.2% of the cases were those of late relapse. The median interval time between relapse and first complete remission was 35.5 mon (range, 1-62 months) . One of the 5 patients with early recurrence and 7 of the 19 with late recurrence cases survived. The 5-year-OS and 5-year-EFS of ETV6-RUNX1 positive children was (89.4±2.4) % and (82.1±6.9) %, respectively. The estimated 10-year-OS and 10-year-EFS of ETV6-RUNX1 positive children was (88.6±2.5) % and (77.3±4.0) %, respectively. The Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. Univariate statistical analysis showed that poor prognostic factors that influenced survival included central nervous system state 2 at diagnosis, poor prednisone response, high risk, gene positivity after induction chemotherapy, as well as MRD positivity and gene positivity at the 12 th week. In the multivariate analysis, only the central nervous system state 2 at diagnosis and MRD positivity at the 12 th week were associated with the outcome. Conclusion:ETV6-RUNX1-positive ALL is a subgroup with a favorable prognosis as per the CCLG-ALL-2008 protocol. Patients with ETV6-RUNX1 should be given more intensive therapy, including hematopoietic stem cell transplantation when they are CNS2 at diagnosis or have high level of MRD at the 12 th week after treatment.