Pathogenic bacteria distribution,drug resistance changes and risk factors of death in patients with acute myeloid leukemia complicated with bloodstream infection / 天津医药

Objective To explore the distribution and drug resistance changes of pathogenic bacteria in adult acute myeloid leukemia(AML)with bloodstream infection,and to analyze risk factors of death of patients.Methods Changes of detection rate of pathogenic bacteria and drug resistance rate of main pathogenic bacteria of 85 patients with AML and bloodstream infection 30 months before confirmed diagnosis(pathogenic bacteria detected from January 2017 to June 2019)and 30 months after diagnosis(from July 2019 to December 2021)were compared.According to the prognosis at 6 months after bloodstream infection,patients were divided into the death group(33 cases)and the survival group(52 cases).Logistic regression analysis was used to analyze risk factors of death in patients with AML complicated with bloodstream infection.Results A total of 98 strains of pathogenic bacteria were detected in 85 patients with AML complicated with bloodstream infection,mainly gram-negative bacteria(65/98,66.33%),followed by Gram-positive bacteria(29/98,29.59%)and fungi(4/98,4.08%).The proportion of fungi(all were candida)detected in the last 30 months was more than that in the first 30 months(P<0.05).There were no significant differences in proportions of gram-negative bacteria and gram-positive bacteria and drug resistance rates of Escherichia coli and Staphylococcus aureus between the late 30 months and the first 30 months(P>0.05).Logistic regression analysis showed that the history of antibiotic use within 1 month before confirmed diagnosis and septic shock were independent risk factors for death in patients with AML complicated with bloodstream infection(P<0.05).Conclusion The main pathogens of adults with AML combined with bloodstream infection are gram-negative bacteria.However,candida infection rate has increased in recent years,and patients with antibiotic use before bloodstream infection and complicated with septic shock are prone to poor prognosis.

Construction of m6A modification related prognostic model in older patients with FLT3 mutated acute myeloid leukemia / 中华老年医学杂志

Objective:To screen m6A modification-related genes, and to establish a prognostic model in patients with FLT3 mutated acute myeloid leukemia(AML), especially in older patients and to evaluate the prognostic efficiency of the model.Methods:Gene expression omnibus(GEO)datasets were used to analyze abnormally expressed m6A enzymes and reading proteins in FLT3 mutated AML; Correlation analysis was used to screen m6A modified-related genes in expression profiles.By integrating TCGA and BEAT data, 83 FLT3 mutated AML patients were included, and 32 of them were older than 60 years.Univariate Cox analysis and Lasso regression were conducted to construct the risk model.Kaplan-Meier curve and time-dependent receiver operating characteristic curve(tROC)were used to evaluate the prognostic efficiency of the model; subgroup analysis was conducted in the older patients.The concordance index(C-index)and calibration curve were used to evaluate the discrimination and accuracy of the model.Results:14 m6A modification enzymes or reading proteins were abnormally expressed in patients with FLT3 mutated AML.Correlation analysis filtered out 2 476 m6A related genes in expression profile.In TCGA and BEAT integrated data, univariate Cox analysis identified 132 prognostic genes.Lasso regression selected seven candidate genes to establish the prognostic risk model, including AKAP9, AVEN, DMCA1, DPYD, FAR2, GPHN and SPECC1L.Kaplan-Meier curve showed that high-risk group of the model had significantly shorter overall survival with a hazard ratio( HR)of 5.08(95% CI: 2.54-10.14, P<0.001).The area under the curve(AUC)in tROC for 1-year survival was 0.83; the C-index of risk model was 0.737.In older patients, the hazard ratio( HR)of the risk model for 1-year overall survival was 3.40(95% CI: 1.25-9.24, P=0.017)with an AUC of 0.79. Conclusions:The risk model based on m6A modified-related genes has some predictive value in assessing the prognosis of patients with FLT3 mutated AML, especially indicative to prognosis prediction in the elderly.

Leucemia aguda bilineal Monocítica/B BCR ABL positivo. Presentación de un caso / Bilinear Acute Monocytic Leukemia/B BCR ABL positive. presentation of a case

RESUMEN Introducción: Las leucemias de fenotipo ambigüo, se clasifican en leucemias indiferenciadas y de fenotipo mixto, éstas a su vez pueden dividirse en bilineales o bifenotípicas y suelen asociarse a mal pronóstico, sobre todo si se acompañan de translocaciones agresivas como la del cromosoma Filadelfia. Reporte de caso Presentamos el caso de una paciente adulta mayor que presentó una leucemia aguda bilineal con la presencia de una población de precursores de linaje monoblástico y otra linfoide B, evaluados por estudios de citometría de flujo, quien además presentó el transcrito BCR-ABL, detectado por estudios de PCR en tiempo real. La paciente cursó con mala evolución y falleció a los 11 días de su diagnóstico. Conclusión: Las leucemias de fenotipo mixto son de mal pronóstico y requieren un diagnóstico precoz por citometría de flujo y Biología molecular para brindar un tratamiento oportuno.

ABSTRACT Background: Leukemias with an ambiguous phenotype are classified as undifferentiated leukemias and mixed phenotypes, these in turn can be divided into bilinear or biphenotypic and are usually associated with a poor prognosis, especially if they are accompanied by aggressive translocations such as the Philadelphia chromosome. Case report: We present the case of an elderly adult patient who presented acute bilinear leukemia with the presence of a population of monoblastic lineage precursors and another, B lymphoid, evaluated by flow cytometry studies, who also presented the BCR-ABL transcript. , detected by real-time PCR studies. The patient had a poor evolution and died 11 days after her diagnosis. Conclusion: Mixed phenotype leukemias have a poor prognosis and require early diagnosis by flow cytometry and molecular biology to provide timely treatment.

Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Venetoclax combined with avapritinib for treatment of refractory/relapsed acute myeloid leukemia with KIT gene mutation: report of 2 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.

Interferon, interleukin 2 combined with lenalidomide for elderly acute myeloid leukemia with minimal residual disease-positive: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the effect of interferon, interleukin 2 (IL-2) combined with lenalidomide in the treatment of acute myeloid leukemia (AML) with minimal residual disease (MRD)-positive.Methods:The clinical data of 1 elderly AML patient with persistent MRD positive treated with interferon, IL-2 combined with lenalidomide in the Affiliated Cancer Hospital of Zhengzhou University in December 2019 were retrospectively analyzed, and the relevant literature was reviewed.Results:The 72-year-old male patient was diagnosed as AML-M 2b with c-kit mutation, the low-risk group according to laboratory related examinations, flow cytometry, genetic testing. The patient did not achieve remission after 1 cycle of standard VA (venetoclax + azacitidine) regimen, and achieved complete remission (CR) after another 1 cycle of IA (idarubicin + cytarabine) induction regimen, followed by consolidation therapy with medium dosage cytarabine and D-CAG (decitabine + cytarabine + aclarubicin + granulocyte colony-stimulating factor) regimen, during which the AML1-ETO fusion gene progressively increased. After programmed death receptor 1 (PD-1) inhibitor-based combination therapy, the AML1-ETO fusion gene remained negative for more than 1 month, and then increased again; subsequently, the patient was treated with the ITI (interferon, thalidomide, and interleukin-2) regimen, and the AML1-ETO fusion gene remained negative for more than 7 months; thalidomide was changed to lenalidomide after the increase again, and AML1-ETO fusion gene remained negative again for 2 years until May 2023. Conclusions:Interferon, IL-2 combined with lenalidomide have a significant therapeutic efficacy in reversing MRD positive and have mild adverse reactions, which can be used as a new option for refractory AML.

Progress in the pathogenesis and the potential treatment targets of EVI1 gene positive acute myeloid leukemia / 白血病·淋巴瘤

Proto-oncogene EVI1 plays an important role in the development of acute myeloid leukemia (AML). AML with EVI1 positive is characterized by abnormal high expression of EVI1 and poor prognosis. The pathogenesis of AML with EVI1 positive has been extensively studied, and the findings suggested that EVI1 can encode a zinc-finger protein that can bind to a variety of DNA. And EVI1 is closely related to the apoptosis, differentiation, proliferation and chemotherapeutic resistance of AML cells. Additionally, with the prevalent use of next-generation sequencing, a number of comutation genes and downstream target genes of AML with EVI1 positive have been discovered. The paper reviews the pathogenesis of AML caused by EVI1 and the potential treatment targets.

Progress of clonal evolutionary basis of FLT3-ITD-mutant acute myeloid leukemia and the effect of its different characteristics on the prognosis / 白血病·淋巴瘤

The incidence of FLT3-internal tandem duplication (ITD) mutation in acute myeloid leukemia (AML) is approximately 20%-30% and FLT3-ITD mutation generally indicates a poor prognosis. Although FLT3 inhibitors have greatly improved the efficacy of AML patients with this type of AML, relapse and drug-resistance increasingly become prominent. ITD mutations lead to dimerization and continuous self-activation of FLT3 in the absence of ligands, and cause non-ligand-dependent phosphorylation. Different characteristics of ITD, including allele ratio, length, insertion site, wild-type mutation content and co-mutated genes, could affect the prognosis of patients. The underlying mechanism of these factors has an important guiding significance for clinical prognosis, drug application and treatment strategy.

Efficacy observation of high-dose non-T-cell depleted PBSC used as grafts for haploidentical HSCT with reduced intensity conditioning in elderly patients with AML/MDS / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of high-dose non-T-cell depleted peripheral blood stem cells (PBSC) used as grafts in haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning (RIC-haplo-HSCT) in the treatment of elderly patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).Methods:The clinical data of AML or MDS 28 patients aged ≥50 years who underwent RIC-haplo-HSCT in the First Affiliated Hospital of Xinjiang Medical University from January 2014 to June 2022 were retrospectively analyzed. All patients received high-dose non-T-cell depleted PBSC as grafts. Anti-CD25 monoclonal antibody and glucocorticoid were added as intensive graft-versus-host disease (GVHD) prophylaxis.Results:All patients achieved hematopoietic reconstruction. The accumulative incidence of grade Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD within 100 d was 22.5% (95% CI 5.1%-39.9%) and 8.2% (95% CI 0-19.2%), respectively. The 3-year cumulative incidence of chronic GVHD was 26.8% (95% CI 7.8%-45.8%), and the incidence of extensive chronic GVHD was 5.9% (95% CI 0-17.1%). The median follow-up time was 35.5 (2-83) months. The 3-year cumulative incidence of relapse and non-relapse mortality was 16.7% (95% CI 2.0%-31.9%) and 12.2% (95% CI 0-25.2%), respectively. The 3-year disease-free survival and overall survival rates were 73.3% (95% CI 56.2%-90.4%) and 79.1% (95% CI 62.2%-96.0%), respectively. Conclusions:High-dose non-T-cell depleted PBSC used as grafts for RIC-haplo-HSCT can achieve good clinical efficacy in elderly patients with AML/MDS.

Clinical features and prognosis of CD7 + relapsed or refractory acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation / 中华检验医学杂志

Objective:To investigate the clinical and molecular features of patients with CD7 +relapsed or refractory acute myeloid leukemia(r/rAML)and the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods:172 r/rAML patients who underwent allo-HSCT in department of hematology, Aerospace Center Hospital between January 1st 2017 and December 31st 2020 were retrospectively analyzed The patients were were divided into CD7 + group( n=75) and CD7 - group( n=97) according to the expression CD7 in the initial immunophenotype. Mann-Whitney U and Chi-square test were used to compare the clinical data, molecular and cytogenetic characteristics of the two groups of patients. Kaplan-Meier method was used to analyze the median progression-free survival (PFS) and median overall survival (OS) of the two groups of patients, and Cox regression screenthe prognostic factors of the patients. Results:The median follow-up time was 19 months. The recurrence rates were 23.71% and 50.67%, respectively in CD7 - and CD7 + group (χ 2=13.428 P<0.001). In relapsed patients, 86.96 percentage of CD7 - group did not express CD7 while 86.84 percentage of CD7 + group expressed CD7. The median PFS was 25 and 5 months in CD7 - and CD7 + group (χ 2=8.695, P=0.003), and the medianOS was 34 and 15 months in CD7 - and CD7 + group (χ 2=2.579, P=0.108). Univariate analysis showed that the CD7 +group, had the lower rates of morphological remission (χ 2=10.014, P=0.002), molecular remission (χ 2=22.809, P<0.001), and more male patients (χ 2=5.281, P=0.022). The incidence of CEBPA double-site mutation was higher (23.4% vs 8.2%, χ 2=8.180, P=0.004) and the rearrangement of RUNX1::RUNX1T1 was lower(4.0% vs18.6%, χ 2=8.362, P=0.004)in CD7 +group than in CD7 -group. Multivariate analysis showed that pre-transplant tumor load was the only prognostic factor for PFS (HR, 1.600; 95% CI, 1.203 to 2.127; P=0.001) and OS (HR, 1.737; 95% CI, 1.273 to 2.369; P<0.001) in r/r AML patients. Conclusion:CD7 expression is a risk factor for poor prognosis in r/r AML patients, and CD7 expression is stable after relapse. Positive CD7 can be used as a target for immune targeted therapy.

Effects of nutritional support on chemotherapeutic efficacy and safety in patients with acute myeloid leukemia / 中国基层医药

Objective:To investigate the effects of nutritional support on chemotherapeutic efficacy and safety in patients with acute myeloid leukemia.Methods:A total of 130 patients with acute myeloid leukemia who received treatment in Lishui Municipal Central Hospital from January 2021 to December 2021 were included in this study. They were divided into a control group and an observation group ( n = 65/group) according to different nutritional support methods. Patients in the control group were given routine intervention, while patients in the observation group were given nutritional support based on routine intervention. These two interventions were administered till 1 month after chemotherapy. Chemotherapeutic efficacy and safety were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [92.3% (60/65) vs. 78.5% (51/65), Z = 4.91, P < 0.05]. After chemotherapy, waist-to-hip ratio, arm girth, and body mass index in the observation group were (0.9 ± 0.1), (25.7 ± 1.2) cm, (21.9 ± 2.1) kg/m 2, respectively, which were significantly greater than (0.8 ± 0.1), (24.4 ± 1.1) cm, (20.6 ± 2.1) kg/m 2 in the control group, respectively ( t = 4.13, 6.63, 3.64, all P < 0.05). Transferrin, albumin, prealbumin, and total serum protein in the observation group were (1.4 ± 0.3) g/L, (27.5 ± 3.1) g/L, (171.3 ± 11.3) mg/L, and (61.2 ± 4.3) g/L, respectively, which were significantly higher than (1.3 ± 0.3) g/L, (25.2 ± 2.9) g/L, (154.3 ± 10.3) mg/L, (56.6 ± 4.0) g/L respectively in the control group ( t = 2.24, 4.48, 8.93, 6.31, all P < 0.05). The scores of emotional state, social status, role cognition, and somatic perception in the observation group were (57.5 ± 4.6) points, (64.5 ± 3.8) points, (56.5 ± 4.1) points, (62.0 ± 4.2) points, which were significantly higher than (47.9 ± 4.2) points, (56.4 ± 3.2) points, (47.7 ± 4.5) points, (55.5 ± 5.4) points in the control group ( t = 12.34, 13.04, 11.55, 7.65, all P < 0.05). The total incidence of adverse reactions in the observation group was 9.2% (6/65), which was significantly lower than 24.6% (16/65) in the control group ( χ2 = 4.43, P < 0.05). Conclusion:Nutritional support can substantially improve chemotherapeutic efficacy in the treatment of acute myeloid leukemia, decrease the incidence of adverse reactions, and is safe. Therefore, nutritional support for patients with acute myeloid leukemia deserves clinical promotion.

Efficacy and safety of AZA combined with HHT and LDAC in the treatment of acute myeloid leukemia patients with 3+ 7 conventional regimen intolerance / 中国医师杂志

Objective:To evaluate the efficacy and safety of azacytidine (AZA) combined with homoharringtonine (HHT) and low-dose cytarabine (LDAC) in the treatment of acute myeloid leukemia (AML) patients with 3+ 7 conventional regimen intolerance.Methods:A retrospective analysis was conducted on the clinical characteristics, efficacy, prognosis, and adverse events of 33 AML patients (15 initially diagnosed and 18 relapsed/refractory) admitted to the Second Xiangya Hospital of Central South University.Results:Among the 33 AML patients treated with this regimen, the median age was 55 years old, 9 patients had a moderate cytogenetic risk, and 18 patients had a high cytogenetic risk. Among the 33 patients, 3 were lost to follow-up and 1 had incomplete data. Among the remaining 29 patients who received AZA+ HHT+ LDAC treatment, the total complete response (CR) rate was 69.0%(20/29), and the total response rate (ORR) was 79.3%(23/29); The median progression free survival (PFS) was 7.0 months. Among the subgroup analysis, including age, gender, Eastern Cooperative Oncology Group (ECOG) score, disease classification, bone marrow progenitor cells, peripheral blood leukocytes, risk stratification, and epigenetic abnormalities, only CR rates and PFS differences were statistically significant among different ECOG scoring groups ( P=0.048; P=0.021). A total of 29 patients underwent 69 AZA+ HHT+ LDAC chemotherapy cycles. Retrospective grading was performed on 69 cycles based on common toxicity criteria for adverse events (CTC AE version 5.0). The most common grade Ⅲ-Ⅳ hematological adverse events were thrombocytopenia (54/69, 78.3%) and granulocytopenia (48/69, 69.6%). Common non hematological adverse events included nausea (19/69, 27.5%), infection (17/69, 24.6%), and hypokalemia (18/69, 26.1%). Conclusions:AZA combined with HHT and LDAC has a good therapeutic effect in the treatment of acute myeloid leukemia, and adverse reaction events are controllable.

One case of myeloid sarcoma with multiple space occupying lesions in the spinal canal / 中华神经科杂志

Myeloid sarcoma (MS) is a tumor mass formed by the proliferation of one or more myeloid primitive cells outside the marrow, which is mostly related to acute myeloid leukemia (AML). It is reported that 2.5% to 9.1% of AML patients have MS, and AML with spinal canal MS is very rare. Spinal canal MS often has an acute onset and is difficult to diagnose. It is easy to cause missed diagnosis and misdiagnosis, which will lead to a delay in accurate diagnosis seriously affecting the treatment and quality of life among these patients. The clinical data, diagnosis and treatment process of a case of MS with multiple space occupying lesions in the spinal canal diagnosed and treated by the Department of Hematology of Peking Union Medical College Hospital are reported, in order to provide reference for clinical workers.

Expression and clinical significance of Flap endonuclease 1 in acute myeloid leukemia / 肿瘤研究与临床

Objective:To investigate the expression level of flap endonuclease 1 (FEN1) in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and its relationship with clinicopathologic features and therapeutic effect, so as to provide a new direction for disease monitoring and targeted therapy in AML patients.Methods:The data of 57 newly treated AML patients and 26 healthy individuals (the healthy control) from the First Clinical College of Guangdong Medical University and Fujian Medical University Union Hospital from November 2018 to December 2020 were retrospectively analyzed. Bone marrow samples of all subjects were collected. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect FEN1 mRNA expression in bone marrow mononuclear cells of all subjects. Bone marrow samples from 9 newly-diagnosed AML patients and 4 healthy controls were collected, and FEN1 protein expression level was detected by using Western blotting. Differences in FEN1 mRNA expression in AML patients achieving different therapeutic effects were compared among AML patients whose data with evaluable efficacy. AML patients were divided into high FEN1 expression group (≥ critical value) and low FEN1 expression group (< critical value), taking the median relative expression level of FEN1 mRNA as the critical value. The correlation of FEN1 expression level with clinicopathologic features, laboratory indicators, cellular and molecular genetic changes in AML patients at initial diagnosis was analyzed.Results:The median relative expression of FEN1 mRNA in newly treated AML patients was higher than that in healthy controls [0.696 (0.025-3.661) vs. 0.246 (0.013-1.237), Z = 1.75, P = 0.041]. Western blotting showed that the expression level of FEN1 protein in AML patients was higher than that in healthy controls. The relative expression of FEN1 mRNA in 15 recurrent AML patients was higher than that in 19 patients patients achieving complete remission (CR) [1.153 (0.047-4.172) vs. 0.259 (0.023-1.148), Z = 2.71, P = 0.009]. The proportion of patients with French-American-British(FAB) type M 5, fever at initial diagnosis and lymph node enlargement in FEN1 high expression group (32 cases) was higher than that in FEN1 low expression group (25 cases) (all P < 0.05). There were no significant differences in the proportion of gender, age, fatigue, pale skin mucosa and large liver and spleen of patients between the two groups (all P > 0.05). At initial diagnosis, the white blood cell count, lactate dehydrogenase, C-reactive protein and bone marrow primitive cell proportion in FEN1 high expression group were higher than those in FEN1 low expression group (all P < 0.05), and the hemoglobin and platelet count in FEN1 high expression group were lower than those in FEN1 low expression group (all P < 0.05). There were no significant differences in procalcitonin level, the proportion of chromosome karyotype, cytogenetic prognosis grade and patients with or without gene mutation between the two groups (all P > 0.05). Conclusions:FEN1 expression is up-regulated in AML patients and further increased in relapsed patients. FEN1 expression in AML patients is associated with adverse clinicopathological features and poor detection results of laboratory indicators, which may become indicators for disease monitoring in AML patients.

Effect of clonal hematopoiesis in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia after chemotherapy / 中华血液学杂志

Objective: To investigate the effect of clonal hematopoiesis (CH) in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia (AML) after chemotherapy. Methods: Retrospective analysis was performed on 86 patients with NPM1(mut) AML newly diagnosed and treated in the First Affiliated Hospital of Soochow University between July 2016 and June 2019. Their clinical data and NGS test results at diagnosis were analyzed. Moreover, bone marrow samples in remission were tested using Sanger sequencing. The log-rank test was used to analyze the difference in hematopoietic recovery, and Cox proportional hazard models were used to analyze the prognostic factors affecting hematopoietic recovery. Results: The median age of the 86 NPM1(mut) AML patients was 50 years (15-69 years). There were 39 males and 47 females. Forty-one patients were induced with intensity chemotherapy ("7 + 3"), whereas 45 patients were treated with low-dose cytarabine-based induction chemotherapy. At diagnosis, The most common mutations in the patients were FLT3, DNMT3A, TET2, and IDH1/IDH2 mutations. CH-associated mutations persisted in 21 patients during remission, and the mutations were DNMT3A, TET2, ASXL1, and IDH1/IDH2. The recovery time of neutrophils in patients with CH-associated mutations in remission was consistent with that in patients without CH in remission (P=0.282) but the recovery time of platelets in patients with CH in remission was significantly longer[26 (95% CI 21-32) days vs 25 (95% CI 23-26) days, P=0.032]. Furthermore, univariate analysis indicated that age, induced chemotherapy program, and CH in remission were risk factors for platelet recovery, whereas multivariate analysis indicated that induced chemotherapy program and CH in remission were independent risk factors for platelet recovery (HR=0.454, P=0.001 and HR=0.520, P=0.027, respectively) . Conclusion: CH in remission delays the hematopoietic recovery of patients with NPM1(mut) AML after chemotherapy.

Minimal residual disease-directed individualized therapy for hematological malignancies / 白血病·淋巴瘤

Minimal residual disease (MRD) has been used for warning of relapse and guiding the therapy selection for hematological malignancies including acute leukemia. Based on MRD-related content reported at the 64th American Society of Hematology (ASH) Annual Meeting, this article discusses the progress of MRD-directed individualized therapy for hematological malignancies with a primary focus on acute myeloid leukemia.

Progress of small molecule targeted therapy for acute myeloid leukemia / 白血病·淋巴瘤

Acute myeloid leukemia (AML) is the most common subtype of acute leukemia in adults with significant heterogeneity. Among hematological malignancies, targeted therapy for AML comes relatively late. Although traditional chemotherapy is still an indispensable part of AML treatment, more and more small molecule targeted drugs have been used in recent years since 2017. This article reviews the progress of small molecule targeted drugs for AML at the 64th American Society of Hematology annual meeting.

Screening and functional verification of key genes in acute myeloid leukemia / 白血病·淋巴瘤

Objective:To explore the key genes related to the development, progression and prognosis of acute myeloid leukemia (AML) based on bioinformatics, and to analyze their functions.Methods:The chip expression profile GSE84881 data set of AML patients including 19 AML samples and 4 normal tissue samples was downloaded from the gene expression omnibus (GEO) database. GEO online tool GEO2R was used to screen the differentially expressed genes (DEG). The DAVID online database was used to make gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEG. The STRING online database was used to analyze the protein interaction (PPI) network of DEG, and the key genes were screened by using the Cytoscape software. The weighted gene co-expression network analysis (WGCNA) was used to build co-expressed network and obtain the central genes.LC-Bio online platform was used to construct Venn diagram and the key genes and central genes in PPI were crossed to finally obtain the true key genes. RNA-seq datasets GSE2191 and GSE90062 of human tissues were downloaded from GEO database to verify the screened key genes. Kaplan-Meier method was used to analyze the effects of key genes on the overall survival (OS) of AML based on the data of GEPIA database.Results:A total of 247 DEG were identified in GSE84881 data set, including 112 up-regulated genes and 135 down-regulated genes. According to the results of GO enrichment analysis, 247 DEG were mainly enriched in the regulation of signal transduction and cell proliferation in the biological process (BP); the cell composition (CC) revealed that these genes were mainly involved in the cytoplasm and exosomes; the molecular function (MF) analysis showed that these genes were mainly enriched in protein binding and calcium binding. Further KEGG pathway enrichment analysis showed that these 247 DEG were mainly involved in NOD-like receptor signal pathway and interleukin 17 (IL-17) signal pathway. And then the 12 key genes were obtained from PPI. WGCNA software was used to screen 13 central genes from GSE84881 dataset and finally 1 real key gene EGF was obtained after taking intersection. Kaplan-Meier method showed that OS time of AML patients in EGF high expression group was decreased than that in EGF low expression group, and the difference was statistically significant( P = 0.044). Conclusions:EGF may be an important diagnosis and treatment target of AML and may become a potential biomarker for clinical treatment and prognosis prediction of AML.

Tislelizumab bridging to umbilical cord blood transplantation therapy for relapsed/refractory acute myeloid leukemia: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To explore the efficacy of tislelizumab combined with umbilical cord blood transplantation (UCBT) in relapsed/refractory acute myeloid leukemia (R/R AML) patients.Methods:The diagnosis and treatment of 1 patient with R/R AML who received tislelizumab bridging to UCBT after the failure of re-induction treatment in the First Affiliated Hospital of Soochow University in November 2021 was retrospectively analyzed.Results:The 59-year-old male patient with R/R AML achieved a complete remission after initial induction chemotherapy regimen of decitabine and venetoclax, and then additional consolidation therapy regimens of decitabine and middle-dose cytarabine, middle-dose cytarabine and idarubicin were performed. The patient relapsed 16 months later and failed to achieve a second remission after re-induction therapy regimens of cladribine, azacitidine, venetoclax combined with chemotherapy, and homoharringtonine, cytarabine combined with granulocyte colony-stimulating factor. Tislelizumab significantly reduced tumor burden and the patient achieved the complete remission after bridging to UCBT. After transplantation, the patient was given maintenance treatment with azacitidine and he had sustained remission without severe transplant-related complications during 9-month follow-up.Conclusions:The use of tislelizumab bridging UCBT can be a potential therapeutic strategy for R/R AML patients.