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.
Antineoplastic Combined Chemotherapy Protocols ; Azacitidine/therapeutic use* ; Cytarabine/therapeutic use* ; Decitabine/therapeutic use* ; Humans ; Myelodysplastic Syndromes/drug therapy* ; Treatment Outcome

OBJECTIVE: To explore the clinical efficacy of decitabine for treatment of patients with myelodysplastic syndrome (MDS) and factors predicting the prognosis. METHODS: The clinical data of 87 patients with MDS treated with decitabine were analyzed retrospectively. The hENT1 mRNA expression and TP53 gene mutation were detected by Q-PCR and gene target sequencing, respectively. The relationship of clinical characteristics and molecular indicators with the clinical response to decitabine was analyzed. RESULTS: In treatment for median 4 (2-17) courses, a total 51 patients (58.6%) showed therapeutic responses, including CR in 17 cases, PR in 12 cases, mCR in 9 cases, HI in 13 cases; 36 (41.4%) patients showed non-response. Univariate analysis showed that the patients with the complex karyotype, monosomal karyotype, chomosome 7 abnormality and Plt count doubling after 1 course treatment had a high CR rate, while the patients with relative high risk by IPSS (intermediate risk 2+ high risk), complex karyotype and Plt count doubling after 1 course had much more high overall remission rate (ORR). The expression level of hENT1 mRNA in MDS patients with response was significantly higher than that in patients without response ［(1.78±1.45 (2) vs 0.96±0.97 (2)(P= 0.002)］. Among 51 patients with therapeutic response, the expression level of hENT1 mRNA in CR group was higher than that in non-CR group ［(2.58±1.44 (2) vs 1.39 ±1.3 (2), P= 0.005)］. Among 52 patients in relative high risk (intermediate risk 2 +high risk), the median OS time of patients with high hENT1 mRNA expression was significantly longer than that of patients with low hENT1 mRNA expression (31 vs 12 months)(P<0.001). Among 87 patients received decitabine treatment, the TP53 gene mutation occured in 11 (12.6%) patients. The ORR in patients with TP53 mutation was high (P=0.04), moreover the patients with TP53 mutation more easily gained CR (P<0.001). Multivariate logistic regression model showed that the complex karyotype, Plt count doubling after 1 course treatment, TP53 mulation and high expression of hENT1 mRNA were the independent prognostic factors for predicting the CR after decitabine treatment. CONCLUSION IPSS staging, complex karyotype, Plt count doubling after 1 course treatment and hENT1 mRNA expression, TP53 gene mutation can be used to predict the tharapeutic efficacy of dectitabine for treatment of MDS.
Decitabine ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose decitabine (DAC) alone for treatment of myelodysplastic syndrome (MDS) Methods: Fifty-one patients with meddle- and high-risk MDS were selected, and were randomly divided into A, B and C groups according to the drug regimens: the therapeutic regimen in A group consisted of low dose DAC 10 mg/(m·d)×7 d; the therapeutic regimen in B group: normal dose DAC 20 mg/(m·d) ×5 d; the therapeutic regimen in C group: low dose DAC+CAG DAC 10 mg/(m·d) d 1-5，cytarabine 10 mg/(m·d) q12h d 1-7, aclaromycin 10 mg/d d 1-4，G-CSF 200 μg/(m·d), d 1-7. All patients in 3 groups were treated for 4 circles. The efficacy and response were compared among 3 groups. RESULTS: The complete remission rates (CR%) in A, B and C groups were 18.75%, 22.22% and 23.53% respectively, and the overall response rate (ORR%) in A, B and C groups were 56.25%, 61.11% and 58.82% respectively, without statistical difference among 3 groups (P＞0.05)．After 1 year of follow-up, the survival rate was not significantly different among 3 groups, the blood cell accounts were higher than the basic value. After 1 course of treatment, the inhibition rate of III-IV grade myelosuppression was statistically significantly different among the 3 groups (P＜0.05), and the infection rate among 3 groups also was statistically different, The incidence of myelosuppression and infection in A group was significantly lower than that in B and C groups. The per capita blood transfusion during the four-month treatment was not statistically different among 3 groups. however, that in the A group was lesser than B and C groups. CONCLUSION The therapeutic efficacy of low dose decitabine alone for treatment of MDS is equal to routine dose decitabine and decitabine plus CAG, but the low dose group shows less myelosuppressive and more safe effects.
Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Decitabine ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Treatment Outcome

Decitabine/therapeutic use* ; Hematologic Diseases/therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Recurrence ; Transplantation Conditioning ; Transplantation, Homologous

OBJECTIVE: To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients. METHODS: Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared. RESULTS: There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group. CONCLUSION The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.
Antineoplastic Combined Chemotherapy Protocols ; Decitabine/therapeutic use* ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Treatment Outcome ; Tretinoin/therapeutic use*

OBJECTIVE: To investigate the efficacy and safety of decitabine combined with half-course pre-excitation for the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 44 cases of newly diagnosed elderly AML admitted in our hospital from January 2016 to December 2017 were selected for the retrospective analysis. The patients were randomly divided into 2 groups: pre-excitation therapy group as control and combined therapy group. The 22 patients in pre-excitation therapy group reccived the routine complete course pre-excitation treatment, 22 patients in combined therapy group received the desitabine combined the half course pre-excitation treatment. The therapentic efficacy and adverse reactions during treatment were compared between 2 groups. All patients were followed-up and the survival rate at 6,12 and 24 months was compared between 2 groups. RESULTS: The remission rate(RR) in the combined therapy group was 72.73%, and that in the control group was 50.00%, with significant statistically difference (P<0.05). The median survival time in combined therapy group (17.82±4.19 months) and control group (12.43±3.71 months) was statistically significant (P<0.05). The rate of adverse reactions of digestive tract in combined therapy group was 40.91%, which was higher than that in control group (18.18%), and the difference of two groups was statistically significant (P<0.05). The incidence of adverse reactions in blood system and bone marrow suppression in combined therapy group was 9.09% and 68.18%, which were lower than those in control group (27.27% and 95.45%), with statistically significant differences (P<0.05). There was no statistically significant difference in the incidence of liver dysfunction, cardiac insufficiency and hair loss between the two groups (P>0.05). The incidence of pulmonary infection, intestinal infection and other complications in combined therapy group was 13.64%, which was lower than that in control group 31.82%, and the difference of two groups was statistically significant (P<0.05). No serious complications such as arteriovenous thrombosis occurred in either group, and no patients died during chemotherapy. CONCLUSION Combination of disitamine and half-course prestimulation treatmentis is a safe and effective and elderly patients with AML shown a good tolerance.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; Decitabine ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the relationship of miR-140 expression level with the therapeutic effect of decitabine, and to explore whether the molecular mechanism is dependent on the regulation of TLR4 expression. METHODS: Forty-seven patients with acute myeloid leukaemia (AML) were enrolled in our study and divided into decitabine combination treatment group (22 cases) and traditional treatment group (25 cases). The clinical efficacy was compared between these two groups. Real-time PCR was used to determine the plasma level of miR-140 in AML patients. Decitabine, miR-140 mimic and miR140 inhibitor were used to treat AML HL-60 cells in vitro, the real-time PCR and Western blot were used to detect the expressions of miR-140, TLR4 and NF-κB at both mRNA and protein levels. RESULTS: Compared with traditional treatment group, decitabine combination treatment group showed more significant clinical efficacy. Plasma miR-140 level in both 2 treatment groups both decreased, but the plasma miR-140 level was higher in decitabine combination treatment group as compared with traditional treatment group. Experiment in vitro showed that 0.3 μmol/L decitabine significantly inhibited the HL-60 cell proliferation accompanied by up-regulation of miR-140 expression and down-regulation of expression of TLR4 and NF-κB. These effects induced by decitabine were partly reversed by pretreating the cells with 200 nmol/L miR-140 inhibitor. CONCLUSION Decitabine-induced up-regulation of miR-140 expression may be related with its chemotherapeutic effects, and miR-140/TLR4/NF-κB pathway may partly mediate the pharmacologic action of decitabine.
Decitabine ; therapeutic use ; Down-Regulation ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; MicroRNAs ; NF-kappa B

OBJECTIVE: To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). METHODS: The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. RESULTS: A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. CONCLUSION The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.
Humans ; Middle Aged ; Blast Crisis/drug therapy* ; Homoharringtonine/therapeutic use* ; Decitabine/therapeutic use* ; Interferons/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Treatment Outcome

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.
Aged ; Male ; Female ; Humans ; Aged, 80 and over ; Decitabine/therapeutic use* ; Retrospective Studies ; Cytarabine/therapeutic use* ; Prognosis ; Mutation ; Leukemia, Myeloid, Acute/genetics*

OBJECTIVE: To investigate the efficacy and mechanism of decitabine maintenance therapy in patients with medium and low-risk acute myeloid leukemia(AML). METHODS: The newly diagnosed medium- and low-risk AML patients in the Second Affiliated Hospital of Anhui Medical University from December 2016 to December 2020 were retrospectively analyzed. Seventy-eight AML patients who were still in remission after consolidation treatment were divided into maintenance treatment group (31 cases) and control group (47 cases). The maintenance treatment patients received decitabine at 20 mg/m2 IV daily for 5 days, every three months for 6 cycles, the control group was only observed and tested regularly. Follow-up was completed by telephone or by viewing outpatient or inpatient medical records. Primary indicators were overall survival (OS), and secondary indicators include relapse-free survival (RFS), tolerance, cellular immune function and analysis of risk factors related to survival. RESULTS: Median RFS in maintenance theatment and control groups was 30.1(26.2-33.8) months and 24.3(21.7-30.3) months (P=0.011), median OS 34.7(29.8-39.7) months and 27.7(24.1-31.3) months respectively（P=0.024）, with a statistically significant difference. For the univariate and multivariate Cox regression analysis, only the minimal residual disease (HR=25.185, P<0.001) and the treatment methods (HR=0.124, P<0.001) affected the PFS and OS of patients. In the maintenance treatment group, CD3⁺T cells, CD8⁺T cells and NK cells increased significantly after decitabine maintenance treatment, and the regulatory T cells decreased significantly (P<0.05). Patients had a low incidence of grade 3-4 adverse events, hematological adverse events were mainly neutropenia and thrombocytopenia, non-hematological adverse events were mainly digestive tract symptoms, and the patient was well tolerated. CONCLUSION Maintenance treatment with decitabine provided benefit survival in patients with medium- and low-risk AML and is well tolerated. The mechanism may be inhibition the proliferation of regulatory T cells, induce and enhance the cytotoxic effect of CD8⁺ T cells on tumor antigens.
Antigens, Neoplasm ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; CD8-Positive T-Lymphocytes ; Decitabine/therapeutic use* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Treatment Outcome