RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
Abstract Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.