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1.
Chinese Journal of Pediatrics ; (12): 357-362, 2023.
Article in Chinese | WPRIM | ID: wpr-985876

ABSTRACT

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.


Subject(s)
Adolescent , Child , Female , Humans , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chromosomal Proteins, Non-Histone/genetics , Cladribine/therapeutic use , Cytarabine/therapeutic use , Daunorubicin/therapeutic use , Etoposide/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Homoharringtonine/therapeutic use , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/genetics , Oncogene Proteins/genetics , Poly-ADP-Ribose Binding Proteins/genetics , Remission Induction , Retrospective Studies
2.
Journal of Experimental Hematology ; (6): 633-642, 2023.
Article in Chinese | WPRIM | ID: wpr-982109

ABSTRACT

OBJECTIVE@#To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).@*METHODS@#The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.@*RESULTS@#Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).@*CONCLUSION@#D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.


Subject(s)
Aged , Male , Female , Humans , Aged, 80 and over , Decitabine/therapeutic use , Retrospective Studies , Cytarabine/therapeutic use , Prognosis , Mutation , Leukemia, Myeloid, Acute/genetics
3.
Journal of Experimental Hematology ; (6): 364-376, 2023.
Article in Chinese | WPRIM | ID: wpr-982068

ABSTRACT

OBJECTIVE@#To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.@*METHODS@#Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).@*RESULTS@#Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).@*CONCLUSION@#Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.


Subject(s)
Humans , U937 Cells , Cytarabine/therapeutic use , Receptors, Interleukin-8A , NF-kappa B , Proto-Oncogene Proteins c-akt , Phosphatidylinositol 3-Kinases , Leukemia, Myeloid, Acute/genetics , Apoptosis , Cell Proliferation , Apoptosis Regulatory Proteins , Proto-Oncogene Proteins c-bcl-2 , RNA, Messenger , Cell Line, Tumor
4.
Journal of Experimental Hematology ; (6): 407-412, 2022.
Article in Chinese | WPRIM | ID: wpr-928728

ABSTRACT

OBJECTIVE@#To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML).@*METHODS@#98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve.@*RESULTS@#After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone.@*CONCLUSION@#The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.


Subject(s)
Humans , Cytarabine/therapeutic use , ErbB Receptors/blood , Leukemia, Myeloid, Acute/drug therapy , Remission Induction , Transforming Growth Factor beta1/blood
5.
Chinese Journal of Hematology ; (12): 287-292, 2022.
Article in Chinese | WPRIM | ID: wpr-929637

ABSTRACT

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.


Subject(s)
Adult , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Cytarabine/therapeutic use , Hematopoietic Stem Cell Transplantation , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Neutropenia , Prospective Studies , Recurrence , Retrospective Studies
6.
Chinese Journal of Hematology ; (12): 383-387, 2022.
Article in Chinese | WPRIM | ID: wpr-929572

ABSTRACT

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/therapeutic use , Daunorubicin/therapeutic use , Homoharringtonine/therapeutic use , Induction Chemotherapy , Leukemia, Myeloid, Acute/genetics , Nuclear Proteins , Prognosis , Remission Induction , Retrospective Studies
7.
Journal of Experimental Hematology ; (6): 1845-1850, 2021.
Article in Chinese | WPRIM | ID: wpr-922345

ABSTRACT

OBJECTIVE@#To investigate the efficacy of high-risk myelodysplastic syndrome (MDS) patients treated by different doses of decitabine (DAC) and its safety.@*METHODS@#Thirty patients with high-risk MDS were all treated by demethylation drug DAC. According to the doses of DAC, 30 patients were divided into 10-day regimen [6 mg/(m@*RESULTS@#The patients were followed up to May 2020, in the 10-day regimen group, 10 cases achieved complete remission (CR), 3 cases achieved partial remission (PR), and 2 cases were progressive disease (PD). Four cases died, including 1 case for heart failure, 2 cases for respiratory failure and 1 case for serious infection. In the 5-day regimen group, 11 cases achieved CR, 1 case achieved PR, 3 cases were PD. Five cases died, including 2 cases for heart failure and 3 for serious infection. The CR rate and ORR of the patients in the two groups were 66.67% vs 73.33%, 86.67% vs 80.00%, respectively, which showed no significant differences, and the efficacy also showed no significant difference. After treatment, the levels of WBC, NE, Hb and PLT of the patients in 10-day regimen group were higher than those in 5-day regimen. In the 10-day regimen group, there were 11 cases of pneumonia, 2 cases of bacteremia, 1 case of skin infection and 1 case of urinary tract infection. While in the 5-day regimen group, 13 cases of pneumonia, 5 cases bacteremia, 1 case of skin infection and 3 cases of urinary tract infection. There were 2 cases with mild gastrointestinal response in the 10-day regimen group, and 7 cases with obvious nausea and anorexia in the 5-day regimen group. The symptoms were relieved after the treatment of acid suppression, stomach protection and antiemetic. The liver, kidney and heart function were monitored. One case liver function damage and 2 cases cardiac insufficiency were observed in the 10-day regimen group. Seven cases regimen cardiac insufficiency and 4 cases regimen liver function damage were observed in the 5-day regimen group.@*CONCLUSION@#10-day regimen and 5-day regimen are equally effective, but 10-day regimen is less myelosuppressive and more safer, which can be applied in clinical.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Azacitidine/therapeutic use , Cytarabine/therapeutic use , Decitabine/therapeutic use , Myelodysplastic Syndromes/drug therapy , Treatment Outcome
8.
Journal of Experimental Hematology ; (6): 677-684, 2021.
Article in Chinese | WPRIM | ID: wpr-880132

ABSTRACT

OBJECTIVE@#To analysis the relationship between different BMI (body mass index) and the clinical characteristics, laboratory examination indexes of newly diagnosed adult patients with acute myeloid leukemia (AML), so as to investigate the effects of BMI to the efficacy of first induction chemotherapy.@*METHODS@#The clinical data of 145 newly diagnosed adult AML patients treated in the First Hospital of Lanzhou University from August 2015 to August 2019 were retrospective analyzed. According to the guidelines for prevention and control of overweight and obesity in Chinese adults, the BMI (kg/m@*RESULTS@#Among the 145 newly diagnosed adult AML patients, there were 71 males and 74 females. The median age was 50 years old(range 18 to 82 years old). There were 21 patients in underweight group (14.5%), 79 patients in normal weight group (54.5%), and 45 patients in overweight and obese group (31.0%). The patients with higher BMI level showed the older in age(P=0.018). There were significant differences in sex between the patients in each group(P=0.035). In overweight and obese patients, the number of male was significantly higher than female. There were no statistical differences in AML classification, comorbidities(Diabetes, hypertension, coronary heart disease), hospital days, whether secondary AML and FLT3 gene mutation among the patients in different BMI groups. There were significant differences in TG of the patients in the different groups, the overweight and obese patients were higher (P=0.007). There were no significant differences in WBC and Hb counts, ALB, TC, HDL, LDL, or LDH between the patients in each BMI group at newly diagnosed. The complete remission rate of the patients in the low body mass group or overweight and obese group were lower than that in the normal body weight group (P=0.035). The rate of documented infection during the first induction chemotherapy were significantly higher for the patients in low body mass group than those in normal weight group or overweight and obese group (P=0.038). There was no statistical difference in chemotherapy regimens, the number of chemotherapy until CR, febrile neutropenia, bleeding, and the time of neutropenia, liver and kidney toxicity among each BMI group. Multivariate analysis showed that overweight and obese (P=0.012) , FLT3 mutation (P=0.015) were the risk factors affecting the CR rate of the patients. And the patients with secondary AML, high-risk type, and newly diagnosed WBC ≥50×10@*CONCLUSION@#In newly diagnosed adult patients with AML, low body mass, overweight and obesity, and FLT3 mutations were the factors reducing the early efficacy of AML patients. There were more adverse reactions induced by chemotherapy in the low body mass group. Therefore, inappropriate BMI level can be a risk factor for assessing the prognosis of adults with newly diagnosed AML.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Body Mass Index , Cytarabine/therapeutic use , Induction Chemotherapy , Leukemia, Myeloid, Acute/drug therapy , Prognosis , Retrospective Studies
9.
Journal of Experimental Hematology ; (6): 333-338, 2021.
Article in Chinese | WPRIM | ID: wpr-880078

ABSTRACT

OBJECTIVE@#To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML).@*METHODS@#Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M@*RESULTS@#Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M@*CONCLUSION@#The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols , Cladribine/therapeutic use , Cytarabine/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Infusions, Intravenous , Leukemia, Myeloid, Acute/drug therapy , Retrospective Studies , Treatment Outcome
10.
Journal of Experimental Hematology ; (6): 1071-1079, 2021.
Article in Chinese | WPRIM | ID: wpr-888520

ABSTRACT

OBJECTIVE@#To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients.@*METHODS@#The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group [75 mg/(m@*RESULTS@#Median follow-up time of all the patients was 15 months. The CR rate and MRD@*CONCLUSION@#The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.


Subject(s)
Aged , Humans , Antineoplastic Combined Chemotherapy Protocols , Cytarabine/therapeutic use , Daunorubicin , Induction Chemotherapy , Leukemia, Myeloid, Acute/drug therapy , Remission Induction , Retrospective Studies
11.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(3): 252-254, July-Sept. 2020.
Article in English | LILACS | ID: biblio-1134035

ABSTRACT

ABSTRACT Introduction:: Most adults with acute myeloid leukemia (AML) will eventually relapse from their disease. The combination of 7-day cytarabine and an anthracycline on days 1-3 (the so called "7 + 3" regimen) can be considered standard of care of younger patients with AML. However, the treatment of the elderly ineligible for intensive chemotherapy remains a challenge. Low-dose of subcutaneous cytarabine or hypomethylating agents (HMA) have been studied this group. There are no studies investigating physician practice variation in treating AML in Brazil. Methods:: We developed a survey with ten questions in order to explore the approach to AML in Brazil. Results:: The sample size comprised 100 hematologists. Most reported regular (63%) or occasional (29%) treatment of AML patients. Karyotype analysis and polymerase chain reaction were available in 88% and 71% of institutions, respectively. Next generation sequencing analysis was used in 7% of instituitions. Younger patients receive the "7 + 3" protocol with continuous infusion of cytarabine and anthracycline in 98% of cases. The preferred anthracycline is daunorubicin (64%), followed by idarubicin (34%). The most prescribed daunorubicin dose was 60 mg/m2 (56%). Consolidation after CR with high cytarabine doses (HIDAC) was indicated by 84% of hematologists and 70% use 3 g/m2 twice a day for 3 days. Elderly and unfit patients received HMA (47%) as the preferred treatment. Conclusion:: We showed that the most prevalent AML treatments were according to current guidelines. There is room to improve on the availability of diagnostic tools and the capacity to perform bone marrow transplantation.


Subject(s)
Humans , Brazil , Leukemia, Myeloid, Acute/therapy , Surveys and Questionnaires , Bone Marrow Transplantation , Idarubicin/therapeutic use , Daunorubicin/therapeutic use , Anthracyclines/therapeutic use , Cytarabine/therapeutic use
12.
Journal of Experimental Hematology ; (6): 1991-1997, 2020.
Article in Chinese | WPRIM | ID: wpr-880004

ABSTRACT

OBJECTIVE@#To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML).@*METHODS@#A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared.@*RESULTS@#The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups.@*CONCLUSION@#Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.


Subject(s)
Aged , Humans , Aclarubicin , Antineoplastic Combined Chemotherapy Protocols , Azacitidine/therapeutic use , Cytarabine/therapeutic use , Decitabine/therapeutic use , Granulocyte Colony-Stimulating Factor , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Patients , Prospective Studies , Treatment Outcome
13.
Rev. méd. Chile ; 147(1): 9-17, 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-991367

ABSTRACT

Background: Mantle cell lymphoma (MCL) has high relapse and mortality rates. There is a survival benefit when treatment is intensified with cytarabine (AraC), hematopoietic cell transplantation (HCT) and maintenance with rituximab. Aim: To assess the outcomes of patients with MCL treated in a university hospital. Material and Methods: Review of an oncology center database and medical records identifying patients with MCL treated between 2006 and 2017. Death dates were obtained from the death certificate database of the National Identification Service. We analyzed the response rate, overall survival (OS) and progression-free survival (PFS). As a secondary objective, the survival impact of AraC, HCT and maintenance with rituximab, was also analyzed. Results: Information on 20 patients aged 62 ± 11 years, followed for a median of 45 months was retrieved. Eighty-five percent were diagnosed at an advanced stage. The most used first-line regime was R-CHOP in 11 patients, followed by R-HyperCVAD in five. Only 47% achieved complete response. 4-year PFS and OS were of 30 and 77% respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) significantly predicted PFS and OS. Maintenance with rituximab or HCT was associated with better PFS (48 vs 21 months, p < 0.01). The exposure to AraC or HCT, in refractory or relapsed disease, was associated with an increase in PFS from 9 to 28 months (p = 0,02) and 4-year OS from 40 to 100% (p = 0.05). OS increased even more, from 25 to 100% in those with high-risk MIPI (p = 0.04). Conclusions: The incorporation of AraC, HCT and maintenance with rituximab in the therapeutic backbone of MCL, especially for high-risk cases, was associated with improved survival.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Hematopoietic Stem Cell Transplantation/methods , Lymphoma, Mantle-Cell/surgery , Lymphoma, Mantle-Cell/drug therapy , Cytarabine/therapeutic use , Rituximab/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Time Factors , Retrospective Studies , Risk Factors , Treatment Outcome , Sex Distribution , Combined Modality Therapy , Age Distribution , Statistics, Nonparametric , Lymphoma, Mantle-Cell/mortality , Kaplan-Meier Estimate , Progression-Free Survival , Neoplasm Recurrence, Local
14.
Rev. Hosp. Ital. B. Aires (2004) ; 37(4): 142-145, dic. 2017. ilus
Article in Spanish | LILACS | ID: biblio-1095740

ABSTRACT

La infección diseminada por Fusarium se ha convertido en un problema creciente en las personas con neoplasias hematológicas malignas, principalmente en pacientes con leucemias agudas; se describen cada vez más casos en aquellos sometidos a un trasplante de médula ósea. No existe un tratamiento óptimo establecido para la fusariosis diseminada. La mortalidad global comunicada de esta infección oscila entre el 50 y el 80%. Se presenta a continuación el caso de un paciente de sexo masculino de 29 años, con diagnóstico de leucemia mieloide aguda, que presenta como complicación una fusariosis diseminada, y logra sobrellevar un trasplante alogénico de médula ósea en el Hospital Italiano de San Justo (Argentina) de forma exitosa. (AU)


Disseminated fusariosis has become an increasing problem in people with hematopoietic neoplasms, mainly in patients affected by acute leukemias, and even more in those who undergo hematopoietic cell transplantation. There is not an optimal treatment for disseminated fusariosis. The global mortality described in the literature is between 50% and 80%. We introduce a case of a 29 year old patient with diagnosis of acute myeloid leukemia complicated with disseminated fusariosis, who copes with an allogeneic hematopoietic cell transplantation with a successful outcome in the "Hospital Italiano de San Justo" (Argentina). (AU)


Subject(s)
Humans , Male , Adult , Leukemia, Myeloid, Acute/surgery , Bone Marrow Transplantation/trends , Fusariosis/therapy , Azacitidine/adverse effects , Tobacco Use Disorder , Transplantation, Homologous , Leukemia, Myeloid, Acute/complications , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Mitoxantrone/administration & dosage , Mitoxantrone/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Cytarabine/administration & dosage , Cytarabine/therapeutic use , Positron-Emission Tomography , Drug Therapy , Fever , Fusariosis/microbiology , Fusariosis/mortality , Fusariosis/epidemiology , Fusariosis/diagnostic imaging , Myalgia , Voriconazole/administration & dosage , Voriconazole/therapeutic use , Filgrastim/therapeutic use , Marijuana Use , Cocaine Smoking , Terbinafine/therapeutic use , Melphalan/administration & dosage , Melphalan/therapeutic use , Anti-Bacterial Agents/therapeutic use
15.
Clinics ; 71(1): 10-16, Jan. 2016. tab, graf
Article in English | LILACS | ID: lil-771947

ABSTRACT

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.


Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Adenocarcinoma/radiotherapy , Brachytherapy/methods , Californium/therapeutic use , Endometrial Neoplasms/radiotherapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brachytherapy/instrumentation , Combined Modality Therapy , Carmustine/therapeutic use , Cytarabine/therapeutic use , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Follow-Up Studies , Melphalan/therapeutic use , Podophyllotoxin/therapeutic use , Survival Rate , Treatment Outcome
16.
Annals of Laboratory Medicine ; : 399-404, 2016.
Article in English | WPRIM | ID: wpr-59857

ABSTRACT

BACKGROUND: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. METHODS: Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared. RESULTS: The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis. CONCLUSIONS: The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation.


Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Bone Marrow/metabolism , Cytarabine/therapeutic use , Daunorubicin , Karyotype , Leukemia, Myeloid, Acute/drug therapy , Mutation , Nuclear Proteins/genetics , Real-Time Polymerase Chain Reaction , Recurrence , Remission Induction , Retrospective Studies , Sequence Analysis, DNA , fms-Like Tyrosine Kinase 3/genetics
17.
Anon.
Rev. cuba. farm ; 49(4)oct.-dic. 2015.
Article in Spanish | LILACS, CUMED | ID: lil-780756

ABSTRACT

FORMA FARMACÉUTICA: bulbo DENOMINACIÓN COMÚN INTERNACIONAL: arabinósido de citosina. COMPOSICIÓN: cada bulbo contiene 100 mg y 500 mg de arabinósido de citosina en solución. CATEGORÍA FARMACOLÓGICA: antineoplásico, agente citotóxico, antimetabolito, analógo de las pirimidinas. FARMACOCINÉTICA: la biodisponibilidad por VO es escasa (menor que 20 %). La distribución es amplia y rápida por los tejidos. Atraviesa las barreras placentarias y hematoencefálica, alcanza el LCR hasta 40‒50 por ciento de la concentración plasmática. Es metabolizado por citidina desaminasa, dando lugar fundamentalmente a arabinósido de uracilo, que es un metabolito inactivo y a trifosfato de aracitidina (activo). La desaminación se produce en el hígado, plasma y tejidos periféricos. Se elimina por la orina (± 80 por ciento) en las primeras 24 h. La vida media de eliminación terminal es 1-3 h. INDICACIONES: leucemia linfocítica y mielocítica aguda y leucemia meníngea. También se emplea en esquemas de segunda o tercera línea de linfomas no Hodgkin y leucemia mieloide crónica. Eritroleucemia. CONTRAINDICACIONES: hipersensibilidad conocida a la citosina. Pacientes con depresión de la médula ósea, enfermedades debilitantes e infecciones virales recientes como varicela o herpes zoster. USO EN POBLACIONES ESPECIALES: LM: datos no disponibles. E: categoría de riesgo D PRECAUCIONES: LM: no se conoce su excreción por la leche humana; no obstante, se recomienda suspender la lactancia materna durante la administración del fármaco. CARCINOGENICIDAD: grupo de riesgo 3. Los efectos depresores de la médula ósea de la citarabina pueden dar lugar a un aumento de la incidencia de infecciones, retardo en la cicatrización y hemorragia gingival. Deben ser cuidadosamente monitoreados los recuentos hemáticos. Si el recuento de leucocitos arroja CAN menor que 1 000 células/mm3 y las plaquetas están por debajo de 50 000 celulas/mm3, el tratamiento debe ser interrumpido. Los valores pueden continuar bajando aún después de que la administración de citarabina sea suspendida. El tratamiento puede reiniciarse cuando existen signos evidentes de recuperación de la médula ósea. Cuando se administran de forma rápida altas dosis por vía IV, los pacientes pueden presentar náusea y vómito durante algunas horas después de la inyección; este problema se presenta en forma menos severa cuando se administra por infusión. En pacientes con enfermedad hepática previa se deberán suministrar dosis menores de citosina, ya que en el hígado ocurre el proceso de detoxificación de este medicamento. Cuando tiene lugar una lisis celular rápida, se deben tomar las debidas precauciones para evitar hiperuricemia y hiperuricosuria y el riesgo de nefropatía por ácido úrico. La neurotoxicidad está asociada con los tratamientos de altas dosis y pueden presentarse como: toxicidad cerebelar aguda o puede ser severa con convulsiones y/o coma, incluso suele ser retardada, hasta 3‒8 días después que el tratamiento haya comenzado. El riesgo de toxicidad cerebelar se incrementa cuando el aclaramiento de creatinina sea inferior a 60 mL/min, edad mayor de 50 años, lesión preexistente del SNC y niveles de fosfatasa alcalina mayor que tres veces el límite superior normal. La conjuntivitis es prevenida y tratada con gotas de solución salina y/o corticosteroides. Como profilaxis, las gotas oculares deben comenzarse de 6 a 12 h antes de iniciar el tratamiento con la citarabina, y continuar hasta 24 h después de haber finalizado esta. El término de altas dosis se define como dosis IV de 2 a 3 g/m2/dosis, cada 12‒24 h, por 4‒12 dosis o de 36 g/m2 en monoterapia, generalmente combinado con otros agentes utilizados en tratamientos con altas dosis de quimioterapia. Puede presentarse el llamado síndrome de la citarabina que se caracteriza por fiebre, mialgia, dolor óseo, dolor torácico, rash maculopapular, astenia y conjuntivitis, puede ocurrir de 6 a 12 h después de la administración de la citarabina. Puede ser tratado de manera eficaz con...(AU)


Subject(s)
Humans , Lymphoma, Non-Hodgkin/therapy , Leukemia, Lymphoid/therapy , Leukemia, Erythroblastic, Acute/therapy , Leukemia, Myeloid/therapy , Cytarabine/therapeutic use
18.
Journal of Korean Medical Science ; : 1416-1422, 2015.
Article in English | WPRIM | ID: wpr-183080

ABSTRACT

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (> or = 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Mercaptopurine/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/therapeutic use , Disease-Free Survival , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Maintenance Chemotherapy/methods , Methotrexate/therapeutic use , Remission Induction , Treatment Outcome
19.
Rev. cuba. hematol. inmunol. hemoter ; 30(2): 98-107, abr.-jun. 2014.
Article in Spanish | LILACS | ID: lil-714387

ABSTRACT

La leucemia mieloide aguda (LMA) es una enfermedad neoplásica de la médula ósea en la que los pacientes con la translocación (8;21) representan un subgrupo con características clínicas y biológicas específicas. Esta alteración citogenética resulta de la fusión de dos genes, dando lugar a una proteína quimérica formada por un dominio N-terminal del gen AML1 y cuatro dominios C-terminales del gen ETO. Esta proteína tiene múltiples efectos en la regulación de la proliferación, la diferenciación y la viabilidad de las células leucémicas. La translocación puede ser detectada como una sola anomalía genética o como parte de anomalías complejas. A diferencia de otros pacientes, el diagnóstico de LMA con t(8;21) puede ser realizado con menos del 20 por ciento de blastos en la médula ósea. La enfermedad se caracteriza por anomalías genéticas adicionales, las células leucémicas muestran un perfil de expresión global de genes y un perfil de microARNs. Usualmente hay un bajo riesgo de recaída de la leucemia después de altas dosis de citosina arabinósido


Acute myeloid leukemia (AML) is a heterogeneous bone marrow malignancy where patients with the cytogenetic t(8;21) abnormality represent a subset with specific clinical and biological characteristics. The translocation results in an in-frame fusion of two genes, resulting in a fusion protein of one N-terminal domain from the AML1 gene and four C-terminal domains from the ETO gene. This protein has multiple effects on the regulation of the proliferation, the differentiation and the viability of leukemic cells. The translocation can be detected as the only genetic abnormality or as part of more complex abnormalities. In contrast to other AML patients, the diagnosis of t(8;21) AML can be made even when less than 20 percent leukemic blasts are present in the bone marrow. The leukemic cells show specific global gene expression and microRNA profiles; and usually there is a low risk of leukemia relapse after high-dose cytarabine therapy


Subject(s)
Humans , Cytarabine/therapeutic use , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/drug therapy
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