OBJECTIVE: To investigate platelet count trajectories after induction therapy with venetoclax combined with azacitidine (VA regimen) in newly diagnosed AML patients and further analyze its clinical significance. METHODS: Clinical date of 50 newly diagnosed AML patients who received VA treatment from March 2020 to July 2023 in Department of Hematology of the First Hospital of Lanzhou University were retrospectively collected. The platelet trajectories after induction chemotherapy were constructed by using group-based trajectory modeling. To study the association between diverse trajectories of platelet counts and compound complete remission (cCR) rate, overall response rate (ORR), minimal residual disease (MRD) negative rate and overall survival (OS) rate. The Cox proportional hazard model was used to evaluate the relationship between platelet trajectory and OS. The logistic regression was used to analyze the influence of individual characteristics on platelet trajectory. RESULTS: Two platelet trajectories were identified based on the model, including platelet slowly increased group (n=31, 62.0%) and platelet rapidly increased group (n=19, 38.0%). There were statistically significant differences in cCR rate, ORR and OS rate between platelet slowly increased group and platelet rapidly increased group (all P < 0.05). The Cox regression analysis showed that platelet rapidly increased group was associated with a decreased risk of mortality compared with platelet slowly increased group (HR=0.153, 95%CI : 0.045-0.527, P =0.003). Logistic regression analysis showed that IDH1/2 mutation (OR =3.908, 95%CI : 1.023-14.923, P =0.046) and platelet transfusion (OR =0.771, 95%CI : 0.620-0.959, P =0.020) were independent influencing factors of platelet trajectory. CONCLUSION The dynamic trajectory of platelet counts in newly diagnosed AML patients who received VA treatment can serve as a significant indicator to observe the efficacy and prognosis. The platelet rapidly increased is an independent protective factor for good prognosis. TheIDH1 /2 mutation and platelet transfusion are independent influencing factors of platelet trajectory.
Humans ; Leukemia, Myeloid, Acute/blood* ; Sulfonamides/administration & dosage* ; Azacitidine/therapeutic use* ; Platelet Count ; Retrospective Studies ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Induction Chemotherapy ; Survival Rate

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the effects of low-dose decitabine on levels of soluble CD44 and GDF11, and hematopoietic function in elderly patients with myelodysplastic syndrome (MDS). METHODS: Ninety-nine patients with senile myelodysplastic syndrome (MDS) admitted to our hospital from October 2015 to October 2017 were divided into group A, B and C according to their treatment, each with 33 cases.The patients in group A were treated with low-dose decitabine, the patients in group B were treated with usual dose of decitabine, and the patients in group C were treated with low-dose decitabine plus G-GSF, cytarabine, and aclarithromycin. The changes of soluble CD44, GDF11 levels and hematopoietic function (sTfR/E) were compared before and after treatment. The clinical remission rate and adverse reaction rate in 3 groups were analyzed. RESULTS: Before treatment, the levels of CD44, GDF11 and sTfR/E were not significantly different between the 3 groups (P＞0.05). After treatment, the levels of CD44 and GDF11 were significantly decreased in these groups, while the serum levels of sTfR/E were significantly increased, and there was no significant difference between the 3 groups (P＞0.05). After treatment, the total effective rates of A, B, and C 3 group were 82.3%, 81.8%, and 78.8%, respectively, without statistically significant difference (P＞0.05). During the treatment, the incidence of non-hemotoxic adverse reactions in group A was 8.8%, significantly lower than that in group B and C (30.3%, 27.3%) (P＜0.05, P＜0.05), the incidence of hemotoxic adverse reactions in group A was 39.4%, significantly lower than that 63.6% and 66.7% in group B and C (P＜0.05, P＜0.05). CONCLUSION Low-dose decitabine alone is effective in treating elderly patients with MDS as compared with conventional dose and combination therapy, moreover can significantly reduce the levels of CD44 and GDF11, improve hematopoietic function and low the adverse reactions. Thereby the low dose of decitabine may be a new choice for clinical treatment of MDS.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; Bone Morphogenetic Proteins ; Decitabine ; administration & dosage ; therapeutic use ; Growth Differentiation Factors ; Hematopoietic Stem Cell Transplantation ; Humans ; Hyaluronan Receptors ; Myelodysplastic Syndromes ; drug therapy ; Treatment Outcome

PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML. MATERIALS AND METHODS: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively. RESULTS: The median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1–14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine. CONCLUSION: Five-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months.
Aged ; Antimetabolites, Antineoplastic/administration & dosage/*therapeutic use ; Azacitidine/*analogs & derivatives/therapeutic use ; DNA Methylation ; Female ; Humans ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Male ; Middle Aged ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo evaluate the clinical efficacy and safety of decitabine and cyclosporine for treatment of low-risk and intermediate-risk-1 myelodysplastic syndrome (MDS) patients.

METHODSThe clinical data of 27 cases of low risk and intermediate-risk-1 MDS during the past 3 years in Tongji hospital were analyzed retrospectively. These MDS patients were divided into 2 groups: decitabine group (11 cases) and cyclosporine group (16 cases). The MDS patients in the 2 groups were treated with ultra low dose of decitabine and cyclosporine A; the curetive efficacy and adverse reactions were evaluated.

RESULTSIn the 11 patients with low-risk and intermediate-risk-1 MDS treated with 2 courses of ultra-low-dose decitabine, 4 cases (36.4%) achieved a hematological improvement, 7 cases (63.6%) showed ineffective, including non-remission in 6 cases (54.5 %) and death in 1 patient (9.1%), total effective rate were 36.4%; 3 cases died within the first year and the overall survival (OS) rate was 72.7%. The causes of death mainly were severe myelosuppression and the associated infection and bleeding. In the 16 patients with low-risk and intermediate-risk-1 MDS treated with cyclosporine (CsA), 10 cases (62.5%) achieved a hematological improvement, 6 cases (37.5%) showed ineffective, the total efficiency of 62.5%; no patients died within 1 year, the 1-year OS was 100%. Changes in neutrophils, hemoglobin and platelet were not significantly different between the two group.

CONCLUSIONThe clinical efficacy of decitabine on low-risk and intermediate-risk-1 MDS has not confirmed to be superior to cyclosporine (P = 0.252). However, the side effects of serious infection and myelosuppression were more severe in decitabine group than that in the cyclosporine group. Moreover, the 1-year overall survival rate in decitabine group is much lower than that in the cyclosporine group (P = 0.027). In regard to the small number of cases and short follow-up time in our this study, the more patients and longer follow-up time are needed to study.

Azacitidine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Cyclosporine ; administration & dosage ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Pancytopenia ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo compare the clinical efficacy and safety among different chemotherapeutic regimens in treatment of refractory/relapsed acute myeloid leukemia (AML).

METHODSThe clinical data of 67 refractory/relapsed AML patients enrolled from September 2008 to April 2013 were collected. The differences of clinical outcome and adverse events among the patients treated with decitabine combined with DAG regimen, CAG regimen or "3+7" regimen were analyzed.

RESULTSAmong 19 patients in decitabine treatment group, 5 (26.3%) achieved complete remission (CR), 4 (21.1%) partial remission (PR), with overall response rate (ORR) of 47.4 %. Of 26 patients in CAG regimen group, 8 (30.8%) achieved CR, 1 (3.8%) PR, with ORR of 34.6%. Of 22 patients in "3+7" regimen group, 4 (18.2%) achieved CR, with ORR of 18.2%. The ORR of decitabine group was significantly higher than that of "3+7" group (P<0.05). However, no significant difference of ORR was observed among the three groups (P>0.05). It was interesting to note that in decitabine group, the marrow blast counts were lower in CR patients compared with those in non-CR patients (P<0.05), while this was not found in "3+7" group (P>0.05) and CAG regimen group (P>0.05). Adverse events in the three groups were similar, mainly including myelosuppression, pulmonary infection, nausea, vomiting and liver dysfunction, and could be well tolerated. Followed- up to September 2013, the median overall survival (OS) of decitabine group, CAG regimen group and "3+7" group after relapse was 7.5, 4 and 3 months, respectively (P>0.05), while significant difference was obtained between decitabine group and "3+7" regimen group (P<0.05).

CONCLUSIONDecitabine combined with DAG regimen is effective and well tolerated in refractory/relapsed AML patients who were unsuitable for intensive chemotherapy and hematopoietic stem cell transplantation, and the patients with low marrow blast counts are more suitable for the application of decitabine combined with DAG regimen.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; administration & dosage ; analogs & derivatives ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Treatment Outcome ; Young Adult

This study was aimed to investigate the effects of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) on DLC-1 gene transcription regulation and molecular biological behaviours in the human multiple myeloma RPMI-8226 cells. The cells were treated respectively with 5-Aza-CdR and TSA alone, or the both combination; the cell proliferation and apoptosis, DLC-1 expression, the protein expression of Ras homolog family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) were examined by CCK-8 method, RT-PCR and ELISA, respectively. The results showed that the 5-Aza-CdR and TSA had cell growth inhibitory and apoptosis-inducing effects in dose-dependent manner (P < 0.05). Compared with a single drug (5-Aza-CdR or TSA alone), the effects were significantly enhanced after treatment with the combination of 5-Aza-CdR and TSA (P < 0.05). DLC-1 was weakly expressed in the control group; the treatment with 5-Aza-CdR alone enhanced its re-expression dose-dependently (P < 0.05). Compared with 5-Aza-CdR alone, 5-Aza-CdR plus TSA enhanced DLC-1 re-expression significantly.Compared with the control, 5-Aza-CdR and TSA significantly decreased RhoA and Rac1 protein expression (P < 0.05). It is concluded that 5-Aza-CdR and TSA can effectively reverse DLC-1 expression of RPMI-8226 cells; TSA has a synergistic effect on its re-expression. 5-Aza-CdR and TSA have significant cell growth inhibitory and apoptosis-inducing effects on RPMI-8226 cells. These effects may be related to the inhibition of Rho/Rho kinase signalling pathway.
Antimetabolites, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; GTPase-Activating Proteins ; metabolism ; Gene Expression ; drug effects ; Humans ; Hydroxamic Acids ; administration & dosage ; pharmacology ; Multiple Myeloma ; genetics ; pathology ; Tumor Suppressor Proteins ; metabolism

This study was purposed to explore the effects of a methylation inhibitor arsenic trioxide (As2O3, ATO) and 5-Aza-2'-deoxycytidine (5-aza-CdR) on the expression of JAK-STAT signal transduction pathway in family members JAK3, TYK2 and hematopoietic cell phosphatase SHP-1 in chronic myeloid leukemia cell line K562 and their roles in pathogenesis of leukemia. The K562 cells were divided into 3 groups:single drug-treated group, combined 2 drugs-treated group, group without drug treatment as control. The concentration of 5-aza-CdR were 0.5, 1, 2 µmol/L; the concentration of ATO was 1, 2.5, 5 µmol/L; the concentration of combined drugs was ATO 1 µmol/L + 5-aza-CdR 0.5 µmol/L, ATO 2.5 µmol/L + 5-aza-CdR 1 µmol/L, and ATO 5 µmol/L + 5-aza-CdR 2 µmol/L. The K562 cells were treated with above-mentioned concentration of drugs for 24, 48 and 72 hours, then the total RNA of cells was extracted, the JAK3, TYK2 and SHP-1 expressions were detected by real-time quantitative-PCR. The results showed that after the K562 cells were treated with ATO and 5-aza-CdR alone and their combination, the expression of SHP-1 mRNA increased, the expressions of JAK3 mRNA and TYK2 mRNA decreased along with increasing of concentration and prolonging of time, displaying the concentration and time-dependency. The SHP-1 negatively related with JAK3 and TYK2. The effect of SHP-1 on JAK3 was significantly higher than that on TYK2. It is concluded that when the K562 cells are treated with ATO and 5-aza-CdR alone and their combination, the expression of SHP-1 is up-regulated and the expressions of JAK3, TYK2 are down-regulated in concentration-and time-dependent manners, moreover the ATO and 5-aza-CdR show synergies demethylation effect. The SHP-1 gene exert effect possibly through inhibiting the JAK/STAT pathway, the JAK3 is affected more than TYK2, the JAK3 may exert more important role in TAK/STAT pathway.
Arsenicals ; pharmacology ; Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; DNA Methylation ; Gene Expression Regulation, Leukemic ; drug effects ; Humans ; Janus Kinase 3 ; metabolism ; K562 Cells ; Oxides ; pharmacology ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; metabolism ; TYK2 Kinase ; metabolism

This study was purposed to compare the clinical efficacy and adverse reactions of low-dose decitabine combined with CAG regimen (aclarubicin, Ara-C, and G-CSF) and CAG regimen alone in intermediate to high-risk myelodysplastic syndromes (MDS), and evaluate the validity and efficacy of the former regimen as new treatment method of intermediate to high-risk myelodysplastic syndromes. A total of 12 patients with intermediate (IR) to high-risk (HR) MDS treated by low-dose decitabine combined with CAG regimen and 10 patients with IR to HR MDS treated by CAG regimen alone were evaluated after treatment of 1 cycle and at least after 2 cycles. The complete remission (CR) after 1 cycle, overall remission rate (ORR), progression free survival (PFS) and overall survival (OS) between them were analyzed. The results showed that 9 patients treated by low-dose decitabine combined with CAG regimen achieved complete remission after 1 cycle, 2 patients achieved partial remission, 1 patient did not show reaction. The complete remission rate was 75.0% and overall response rate was 91.7%. The median time of disease free survival was 9 months (0-27 months). The median overall survival time was 16 months (3-28 months). 4 patients suffered from pulmonary infection after treatment and then were all cured after treatment with anti-infective therapy. The 5 patients treated by CAG regimen alone achieved complete remission,3 patients achieved partial remission, 2 patients showed non-reaction. The complete remission rate was 50.0% and overall response rate was 80.0%. The median time of disease free survival was 6 months(0-18 months). The median overall survival time was 13 months(3-31 months), 4 patients suffered from pulmonary infection, 1 patient suffered from enteric infection and 1 patient suffered from Escherichia coli septicemia after treatment, all of them becomed better after active treatment. Two groups of patients all had no serious adverse reactions, All patients could tolerate, no severe complication-related death occurred in them. The statistical analysis indicated that the patients treated with low-dose decitabine combined with CAG regimen had longer progression free survival time than those treated with CAG regimen alone, and had longer overall survival time but did not have statistically significant. It is concluded that low-dose decitabine combined with CAG regimen has better clinical efficacy for patients with intermediate to high-risk MDS and did not increase risk for them. It is worth to apply in clinic.
Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; administration & dosage ; analogs & derivatives ; Cytarabine ; therapeutic use ; Disease-Free Survival ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Remission Induction ; Treatment Outcome

This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.
Aclarubicin ; administration & dosage ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Azacitidine ; administration & dosage ; analogs & derivatives ; Core Binding Factor Alpha 2 Subunit ; metabolism ; Cytarabine ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; RUNX1 Translocation Partner 1 Protein ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Young Adult