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1.
Cancer Research and Clinic ; (6): 246-251, 2023.
Article in Chinese | WPRIM | ID: wpr-996220

ABSTRACT

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.

2.
Chinese Journal of Neurology ; (12): 915-917, 2023.
Article in Chinese | WPRIM | ID: wpr-994914

ABSTRACT

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.

3.
Journal of Chinese Physician ; (12): 1159-1164, 2023.
Article in Chinese | WPRIM | ID: wpr-992436

ABSTRACT

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.

4.
Chinese Journal of Hematology ; (12): 845-850, 2023.
Article in Chinese | WPRIM | ID: wpr-1012242

ABSTRACT

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.


Subject(s)
Female , Humans , Male , Middle Aged , Adolescent , Young Adult , Adult , Aged , Clonal Hematopoiesis , Hematopoiesis , Leukemia, Myeloid, Acute/genetics , Mutation , Nucleophosmin , Prognosis , Retrospective Studies
5.
Journal of Leukemia & Lymphoma ; (12): 505-509, 2023.
Article in Chinese | WPRIM | ID: wpr-989012

ABSTRACT

The acute myeloid leukemia and myelodysplastic syndromes are common myeloid neoplasms for which allogeneic hematopoietic stem cell transplantation is one of the main curative therapies. In high-risk patients, the relapse rate can be more than 40%, and patients with post-transplantation relapses have a very poor prognosis, so preventing relapse after transplantation is crucial. The maintenance therapy is a group of interventions to prevent relapse when morphological, molecular biological and cytogenetic results are constantly negative after transplantation. Currently, the commonly used maintenance therapy is the application of demethylating drugs, targeted drugs, etc., but their necessity, medicine plan, adverse effects, multi-drug combinations, and other aspects need to be studied urgently. This article will systematically describe the progress of post-transplantation maintenance therapy for high-risk myeloid neoplasms based on drug classification.

6.
Journal of Leukemia & Lymphoma ; (12): 411-415, 2023.
Article in Chinese | WPRIM | ID: wpr-989001

ABSTRACT

Objective:To explore the clinical short-term efficacy of venetoclax (Ven) combined with azacitidine (AZA) in treatment of newly treated and relapsed/refractory patients with acute myeloid leukemia (AML).Methods:The data of 18 newly treated and relapsed/refractory patients with AML who received Ven+AZA treatment in Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from April 2020 to June 2022 were retrospectively analyzed. The complete remission or complete remission with incomplete recovery of blood cell count (CR/CRi) and objective remission rate (ORR) [calculated as CR/CRi+partial remission (PR)] were analyzed in newly treated and relapsed/refractory patients or patients with different gene mutations. The patients were followed up until June 30, 2022, and the overall survival (OS) of relapsed/refractory patients was analyzed. The occurrence of adverse reactions was summarized.Results:The median age of the 18 patients was 58 years old (23-81 years old), 8 were males and 10 were females; 6 were newly treated and 12 were relapsed/refractory; the median follow-up time was 3 months (1-15 months). In 6 newly treated patients, after the first cycle of Ven+AZA, 5 cases achieved CR/CRi, and the ORR was 83.3% (5/6). In 12 relapsed/refractory patients, after the first cycle of Ven+AZA, 5 cases achieved CR/CRi, 3 achieved PR, and the ORR was 66.7% (8/12). Among the 18 patients, 7 cases had FLT3-ITD/TKD mutation, after the first cycle of Ven+AZA, 1 case achieved CR/CRi, 1 case achieved PR, and the ORR was 28.6% (2/7); 3 cases had NPM1 mutation combined with FLT3-ITD/TKD mutation, 1 case achieved CR/CRi, and the ORR was 33.3% (1/3); 4 cases had IDH1/2 mutation, and 3 cases of them combined with FLT3-ITD/TKD mutation, all of which were non-remission, and the other 1 relapsed/refractory patient combined with K/NRAS mutation achieved CR/CRi; among the 4 cases with K/NRAS mutation, 2 cases combined with FLT3-ITD/TKD mutation, including 1 case of NR and 1 case of PR, and the other 2 cases achieved CR/CRi, the ORR was 75.0% (3/4). Of the 12 relapsed/refractory patients, 6 died by the end of follow-up, with a median OS time of 2.6 months (1- 8 months), including 4 cases of disease progression and 2 cases of disease relapse; the 6 surviving patients had stable disease. All the 18 patients had ≥grade 3 hematologic adverse reactions, and non-hematologic adverse reactions included lung infection, nausea, vomiting and diarrhea.Conclusions:Ven+AZA treatment for newly treated and relapsed/refractory AML patients results in a high response rate with tolerable adverse reactions, but it is not effective in AML patients with FLT3-ITD/TKD mutation.

7.
Journal of Leukemia & Lymphoma ; (12): 385-393, 2023.
Article in Chinese | WPRIM | ID: wpr-988997

ABSTRACT

Objective:To investigate the expression of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in patients with acute myeloid leukemia (AML) and its relationship with clinical features and prognosis, and to examine its effect on PD-1-positive natural killer (NK) cells against AML cells in vitro.Methods:The bone marrow samples of 65 AML patients and the peripheral blood of 32 AML patients diagnosed in Affiliated Cancer Hospital of Zhengzhou University from July 2019 to December 2020 were prospectively collected, and the peripheral blood of 24 healthy people was taken as healthy control. The expression level of PD-L1 in bone marrow tumor cells and expression level of PD-1 in peripheral blood NK cells were detected by flow cytometry. The correlations of PD-1 expression in bone marrow tumor cells and PD-1 expression in NK cells with the clinicopathological features, curative effect and prognosis of patients were analyzed. Flow cytometry was used to detect the expression level of PD-L1 in AML cell line THP-1 (target cells) and the expression level of PD-L1 in NK cell line NKL (effector cells). THP-1 cells treated with and without 25 μmol/L of PD-L1 inhibitor fraxinellone were used as experimental group and control group, and co-cultured with NKL cells at different effector-to-target ratios. The apoptosis of THP-1 cells and the expression of NKG2D in NKL cells were detected by flow cytometry, the cell proliferation status was detected by CCK-8 and the cell proliferation inhibition rate was calculated; the levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of co-culture system were detected by enzyme-linked immunosorbent assay (ELISA).Results:The proportion of AML patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in the healthy control group [38.5% (25/65) vs. 8.3% (2/24), P = 0.029]. The proportion of AML patients with PD-1-positive expression in peripheral blood NK cells was higher than that in the healthy control group [40.6% (13/32) vs. 12.5% (3/24), P = 0.035]. There were no statistical differences in sex, age, hemogram, proportion of primordial cells, risk stratification, chromosomal karyotype, gene mutation (except NPM1 gene), fusion gene and French-American-British cooperative group (FAB) typing between patients with PD-L1 positive and negative in bone marrow tumor cells and between patients with PD-1 positive and negative in peripheral blood NK cells (all P > 0.05). In relapsed/refractory patients, the proportion of patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in newly treated patients [58.8% (10/17) vs. 31.2% (15/48), P = 0.045]. There was no significant difference in the proportion of patients with PD-1-positive expression in peripheral blood NK cells between relapsed/refractory patients and newly treated patients [(38.5% (5/13) vs. 42.1% (8/19), P = 0.837]. There was no statistical difference in complete remission (CR) rate between PD-L1 positive and negative patients [69.6% (16/23) vs. 74.3% (26/35), P > 0.05]. There was no statistical difference in CR rate between PD-1 positive and negative patients [66.7% (8/12) vs. 70.6% (12/17), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-L1 positive and negative patients [12.5% (2/16) vs. 19.2% (5/26), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-1 positive and negative patients [25.0% (2/8) vs. 16.7% (2/12), P > 0.05]. Flow cytometry showed that the positive rate of PD-1 in NKL cells was (67±6)% and the positive rate of PD-L1 in THP-1 cells was (85±5)%. After co-culture with NKL cells, the apoptotic rate and proliferation inhibition rate of THP-1 cells were higher in the experimental group compared with the control group, the expression of NKG2D on the surface of NKL cells was elevated, and the levels of IFN-γ and TNF-α in the co-culture supernatant were increased. Conclusions:In AML patients, the expression of PD-L1 in bone marrow tumor cells is high, and the expression of PD-1 in peripheral blood NK cells is also high. The expression of PD-L1 in bone marrow tumor cells of relapsed/refractory AML patients is higher than that of newly treated patients. Inhibition of PD-L1 expression in THP-1 cells can enhance the tumor killing activity of NKL cells in vitro. The mechanism may be that inhibition of PD-L1 expression in THP-1 cells up-regulates the expression of NKL cell activated receptor NKG2D and promotes the secretion of IFN- γ and TNF- α.

8.
Journal of Leukemia & Lymphoma ; (12): 381-384, 2023.
Article in Chinese | WPRIM | ID: wpr-988996

ABSTRACT

MLL3 is also known as lysine methyltransferase 2C (KMT2C). The mutation of MLL3 can occur in a variety of human cancers, including leukemia, liver cancer, and stomach cancer. The effect of MLL3 in different cancers is also different, for example, MLL3 is carcinogenic in pancreatic and liver cancer, while it acts as a tumor suppressor in acute myeloid leukemia and esophageal squamous cell carcinoma. The effects of genes in tumors depend on certain environment and conditions, and the mechanism of the suppressive effect of MLL3 in leukemia is still not clear. This paper reviews the research progress of the antitumor mechanism of MLL3 in leukemia.

9.
Journal of Leukemia & Lymphoma ; (12): 377-381, 2023.
Article in Chinese | WPRIM | ID: wpr-988995

ABSTRACT

Acute myeloid leukemia (AML) patients with FLT3 mutation have a high risk of recurrence and poor prognosis. The first generation of drugs targeting FLT3 represented by sorafenib show poor selectivity and efficacy in the treatment of AML, whereas the new second-generation FLT3 inhibitors represented by gilteritinib have a stronger inhibitory effect on FLT3, higher specificity and lower off-target toxicity, which greatly improves the outcomes of AML patients with FLT3 mutation. This article reviews the action mechanism and the clinical progress of gilteritinib.

10.
Journal of Leukemia & Lymphoma ; (12): 343-347, 2023.
Article in Chinese | WPRIM | ID: wpr-988991

ABSTRACT

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

11.
Journal of Leukemia & Lymphoma ; (12): 335-342, 2023.
Article in Chinese | WPRIM | ID: wpr-988990

ABSTRACT

Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.

12.
Journal of Leukemia & Lymphoma ; (12): 215-220, 2023.
Article in Chinese | WPRIM | ID: wpr-988974

ABSTRACT

Objective:To explore the prognostic predictive value of detecting minimal residual disease (MRD) after 2 courses of hypomethylating agents (HMA) combined with low-dose induction chemotherapy in patients with acute myeloid leukemia (AML).Methods:The data of 43 newly diagnosed AML patients treated by HMA combined with low-dose induction chemotherapy in Jingjiang People's Hospital of Jiangsu Province from January 2016 to January 2021 were retrospectively analyzed, and the bone marrow MRD levels were detected by multiparametric 10-color flow cytometry (MFC) after 1 course and 2 courses of chemotherapy. Patients were divided into three groups according to MRD levels: the group with negative MRD after 1 course of induction chemotherapy (MRD-1 group), the group with negative MRD after 2 courses of induction chemotherapy (MRD-2 group), and the group without negative MRD after 2 courses of induction chemotherapy (MRD+ group). Kaplan-Meier method was used to draw the progression-free survival (PFS) and overall survival (OS) curves of all patients and each group, and log-rank test was performed to compare them; the influencing factors for OS were analyzed using univariate and multivariate Cox proportional hazards models.Results:Among the 43 patients, 17 patients (39.5%) were in the MRD-1 group, 14 patients (32.6%) were in the MRD-2 group, and 12 patients (27.9%) were in the MRD+ group. There were no statistical differences among the 3 groups in gender, age, hemoglobin level at initial diagnosis, white blood cell count, platelet count, lactate dehydrogenase level, disease subtype, WT1 expression, karyotype, and genetic risk stratification (all P > 0.05). The median follow-up was 15 months (1-67 months). Survival analysis showed a median OS time of 21 months (95% CI 15 months -not reached) in 43 patients and a median PFS time of 12 months (95% CI 9-18 months) in 29 patients included in the PFS analysis; PFS and OS in the MRD-1 and MRD-2 groups were better than those in the MRD+ group (all P < 0.01), and the differences in PFS and OS between the MRD-1 and MRD-2 groups were not statistically significant (both P > 0.05); the median PFS time was 5 months (95% CI 2 months-not reached) in the MRD+ group, the median PFS time was 15 months (95% CI 7 months-not reached) in the MRD-1 group, and the median PFS time was 18 months (95% CI 11 months-not reached) in the MRD-2 group; the median OS time in the MRD+ group was 9 months (95% CI 7 months-not reached), the median OS time was not reached in the MRD-1 group, and the median OS time was 38 months (95% CI 38 months-not reached) in the MRD-2 group. Multivariate Cox regression analysis showed that age ( HR = 1.080, 95% CI 1.004-1.160, P = 0.038), MRD status (MRD-1 vs. MRD+: HR = 0.125, 95% CI 0.031-0.507, P = 0.004; MRD-2 vs. MRD+: HR = 0.146, 95% CI 0.037-0.577, P = 0.006) were independent influencing factors for OS in AML patients. Conclusions:The survival is good in AML patients with MRD negative conversion after both 1 course and 2 courses of HMA combined with low-dose induction chemotherapy, and both are better than that in patients with positive MRD after 2 courses of chemotherapy.

13.
Journal of Leukemia & Lymphoma ; (12): 161-165, 2023.
Article in Chinese | WPRIM | ID: wpr-988968

ABSTRACT

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.

14.
Journal of Leukemia & Lymphoma ; (12): 153-157, 2023.
Article in Chinese | WPRIM | ID: wpr-988966

ABSTRACT

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.

15.
Journal of Leukemia & Lymphoma ; (12): 82-85, 2023.
Article in Chinese | WPRIM | ID: wpr-988957

ABSTRACT

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.

16.
Journal of Leukemia & Lymphoma ; (12): 12-17, 2023.
Article in Chinese | WPRIM | ID: wpr-988946

ABSTRACT

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.

17.
Chinese Journal of Hematology ; (12): 124-131, 2023.
Article in Chinese | WPRIM | ID: wpr-969687

ABSTRACT

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.


Subject(s)
Adult , Humans , Male , Middle Aged , Prognosis , Remission Induction , Retrospective Studies , Leukemia, Myeloid, Acute/drug therapy , Induction Chemotherapy , Recurrence , Hematopoietic Stem Cell Transplantation
18.
Chinese Journal of Hematology ; (12): 366-372, 2023.
Article in Chinese | WPRIM | ID: wpr-984631

ABSTRACT

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.


Subject(s)
Humans , U937 Cells , RUNX1 Translocation Partner 1 Protein , Leukemia/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Oncogene Proteins, Fusion/genetics , Leukemia, Myeloid, Acute/genetics
19.
Chinese Journal of Primary Medicine and Pharmacy ; (12): 1175-1179, 2023.
Article in Chinese | WPRIM | ID: wpr-991881

ABSTRACT

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.

20.
Einstein (Säo Paulo) ; 21: eAO0117, 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1421375

ABSTRACT

ABSTRACT Objective To characterize the immunophenotypic profile of acute leukemias in the population of the state of Bahia, Brazil. Methods This is a descriptive, retrospective study. From 2014 to 2018, 796 new cases of acute leukemia were evaluated. The data were obtained from analysis of reports and records of tests performed by flow cytometry immunophenotyping. All individuals of all age groups diagnosed as acute lymphoblastic leukemia or acute myeloid leukemia were included in the study. Demographic variables and expression of leukemia antigens were evaluated. Results Most cases were diagnosed as acute myeloid leukemia and 42.7% as acute lymphoblastic leukemia. Significant differences were found in expression of markers in acute leukemias when age groups were compared, as well as in demographic characteristics. B-cell acute lymphoblastic leukemia was more prevalent than cases of T-cell origin. Assessing the aberrant markers in acute myeloid leukemias, the non-acute promyelocytic leukemia group presented expression of CD7 and CD56 as the most frequent ones. In B-cell acute lymphoblastic leukemia, the most frequent aberrant markers were CD66c, CD13 and CD33. Conclusion Significant differences were found as to several antigens when comparing adults and children, and these findings may contribute to future studies correlating the phenotypic profile to genetic characteristics and therapeutic response, including specific antigen therapies, which may be better targeted.

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