[Outcomes of DNMT3A+ Myelodysplastic Syndrome Patients Treated with Decitabine].

OBJECTIVE: To study therapeutic efficacy and side effects of single decitabine for DNMT3A+ myelodysplastic syndrome (MDS) patients. METHODS: The clinical characteristics, efficacy and side effects of 59 myelodysplastic syndrome patients received the decitabine therapy in our center from January 2015 to December 2018 were retrospectively analyzed. Based on gene mutations, these patients were divided into 2 groups: DNMT3A+ MDS patients (n=27) and DNMT3A- MDS patients (n=32). All patients in two groups were treated with decitabine for 4 circles. The efficacy and side effects in the two groups were compared. RESULTS: The median age of patients in DNMT3A+ MDS group was 56.2 (37-81) which was no statistic difference from DNMT3A- MDS group. And there was no statistical difference including age, white blood cells, hemoglobin and platelet count between the two groups (P＞0.05). The ORR and complete response (CR) rate of DNMT3A+ group were 70.37% and 40.74%, the ORR and CR rate of DNMT3A- group were 40.63% and 21.88% respectively. Significant differences were observed in ORR rate (P=0.035) between two groups. However, significant differences did not found in CR rate (P=0.159) between two groups, The similar adverse reaction was observed in DNMT3A+ and DNMT3A- MDS patients. Among the 59 patients, 21 patients showed TP53+ mutation. DNMT3A+/TP53+ MDS patients (n=13) had similar ORR and CR compared with the DNMT3A-/TP53+ MDS patients (n=8) (P＞0.05). The overall survival (OS) in DNMT3A+ MDS group and DNMT3A- MDS group were 29.1±13.4 months and 27.8±14.4 months, respectively, no significant differences between two groups were observed (P=0.475). CONCLUSION: Decitabine treatment is an effective and safe for DNMT3A+ MDS patients, but not shows better survival advantage.

[Clinical Efficacy of Low-Dose Bortezomib-Based Triple Combination Therapy in the Treatment of Elderly Multiple Myeloma].

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose bortezomib-based triple combination therapy in the treatment of elderly multiple myeloma(MM). METHODS: Fifty-eight patients with elderly multiple myeloma were selected. And according to the drug rigimen the patients were randomly divided into three groups. Group A: patients received low-dose bortezomib(0.7mg/m2) on day 1, 4, 8 and 11; cyclophosphamide (0.5 g/m2) d 1, d 8; dexamethasone d 1-2,d 4-5, d 8-11, d 11-12. Group B: patients received bortezomib (1.3 mg/m2) on day 1, 4, 8 and 11; cyclophosphamide (0.5 g/m2) d 1, d 8; dexamethasone d 1-2, d 4-5, d 8-11, d 11-12. Group C: patients received bortezomib(0.7 mg/m2) on day 1, 4, 8 and 11; dexamethasone d 1-2, d 4-5, d 8-11, d 11-12. All patients in three groups were treated for 4 circles. The efficacy and response of the three groups were compared. RESULTS: The complete remission (CR) rate in the three groups was 31.58%, 38.09% and 27.78%. And the overall response (ORR) rate of the three groups was 68.42%, 66.67% and 55.56%, there was no statistical difference among the three groups (P＞0.05). The Hb level in MM patients with anemia after treatment was higher than the basic value. There were no statistical differences in percapita red blood cell transfusion, the incidence of bone marrow suppression and infection during 4 courses treatment among 3 groups, but the incidence of peripheral neuropathy, gastrointestinal reaction and herper zoster in group A was significantly lower than that in group B and C, moreover there was statistical difference. After the follow-up for 1 year, there was no significant difference in the survival rate among 3 groups. CONCLUSION: The efficacy of low dose bortezomib-based triple combination therapy for the patients with elderly multiple mycloma is same efficacy as of standard dose bortezomib-based triple combination therapy, but the incidence of perpheral neuropathy, gastrointestinal reaction and herper zoster is lower, the patients have better torelonce to low dose bortezomib-based triple combination therapy regimen, suggesting that this therapy possesses the efficacy of less adverse reactions and more high safety in treatment of patients with elderly muitipe myelome.

[Clinical Efficacy and Prognosis of Double-Hit Multiple Myeloma Patients with Deletion P53 Treated with Regimen Based on Bortezomib].

OBJECTIVE: To investigate the clinical efficacy and prognosis of double-hit multiple myeloma patients with deletion P53 treated with regimen based on bortezomib. METHODS: The ethnical data from 186 newly diagnosed MM patients hospitalized in the Department of Hematology of Harrison International Peace hospital from January 2012 to January 2019 were analyzed retrospectively. The fluorescent in situ hybridization (FISH) and G-binding staining were used to detect cytogenetic abnormalities (P53 deletion, lq21 amplification and IgH rearranagement) for analyses of complete remission (CR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients treated with bortezomib for 4 circles. RESULTS: In 186 patients, simple P53 deletion was 14 cases, 1q21 amplification and P53 deletion were found in 11 cases (A group), t (14;16) and P53 deletion in 7 cases (B group), t (4;14) and P53 deletion in 9 cases (C group). The complete remission rate (CR%) of above-mentioned three groups was 27.27%, 28.57% and 33.33% respectively, and the ORR of the three groups was 54.54%, 57.14% and 55.56%, respectively, there was no statistically significant difference between the three groups (P＞0.05). The patients with 1q21 amplification and P53 deletion had shorter OS and PFS time (P=0.041, P=0.046). The double-hit patients with 1q21 amplification showed shorter OS time, compared with the patients with P53 deletion (P=0.027). The double-hit patients with t(14;16) and t(4;14) showed shorter OS time (P=0.871, P=0.276) and PFS time (P=0.955, P=0.379) than those of the patients with P53 deletion. CONCLUSION: P53 deletion and 1q21 amplification are an adverse prognostic factor of early recurrence and short lifetime in patients with newly diagnosed double-hit MM.

[Effects of Low-Dose Decitabine on Soluble CD44, GDF11 Levels and Hematopoietic Function in Elderly Patients with MDS].

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.

[Clinical Efficacy of Low-Dose Decitabine alone for Treatment of Myelodysplastic Syndrome].

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/(m2·d)×7 d; the therapeutic regimen in B group: normal dose DAC 20 mg/(m2·d) ×5 d; the therapeutic regimen in C group: low dose DAC+CAG DAC 10 mg/(m2·d) d 1-5，cytarabine 10 mg/(m2·d) q12h d 1-7, aclaromycin 10 mg/d d 1-4，G-CSF 200 µg/(m2·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.

[Effects of Scutellaria Barbata on VEGF Expression in K562 Cells].

OBJECTIVE: To investigate the anti-angiogenesis effect of Scutellaria barbata extract(SBE) on chronic myeloid leukemia(CML) K562 cell line in vitro. METHODS: The proliferating activity after treating K562 cells with 0.5,1.0,2.0 and 4.0 g/ml SB for 24, 36, 48 hours were assessed by MTT assay. The level of vascular endothelial growth factor(VEGF) in the culture supematant of K562 cells was determined by ELISA; and the expression of VEGF mRNA was detected by RT-PCR. RESULTS: MTT assay showed that SBE could inhibit the proliferation of K562 cells in a dose-dependent manner (r=0.56); ELISA displayed that the concentration of VEGF in K562 cells in blank-control group was most high; after intervention of K562 cells by SBE (0.5,1.0,2.0 and 4.0 g/ml) for 48 h, the concentration of VEGF decreased, the comparison between different groups showed significant differences (P<0.05); after treatment with SBE for 48 h, the expression of VEGF mRNA in K562 cells decreased, the gray scale ratio of target gene/ß-actin declined, and the difference between various groups was statistically significant (P<0.05). Conclution: SBE can inhibit K562 cell proliferation, its action mechanism may related with the VEGF level concentration in K562 cells and down-regulation of VEGF mRNA expression.

[Quantitation of Circulating Cell-free DNA in Patients with Lymphoma and Its Clinical Significance].

OBJECTIVE: To evaluate the value of circulating cell-free DNA (CFDNA) quantification for screening lymphoma, to analyse the relationship of circulating CFDNA with curative effect under standard therapeutic schedule, and to determine whether circulating CFDNA could be applied to monitor and prognosticate lymphoma. METHODS: The peripheral blood samples from 32 patients(21 cases of lymphoma and 11 cases of lymphadenitis) with superficial lymph node enlargement were collected, 9 healthy volunteers were as the normal control. Fluorescent quantitative PCR was used to detect the circulating CFDNA in 3 groups. Then, the relationship of circulating CFDNA with common characteristics of lymphoma was analysed, so as to evaluate the importance of circulating CFDNA to the curative effect and prognosis. RESULTS: The circulating CFDNA level in patients with lymphoma was higher than that in patients with lymphadenitis and healthy volunteers (56.71±50.61) ng/ml vs (19.21±15.52) ng/ml and (8.26±7.06) ng/ml (P<0.05), but the difference between the latter 2 was not statistically significant (P=0.118). The circulating CFDNA level in lymphoma significantly correlated with the level of lactate dehydrogenase(LDH) (P<0.05). ROC analyses revealed that the detection of plasma DNA could discriminate the lymphoma from normal controls with 75% sensitivity, 85% specificity and with a cut-off value of 24.67 ng/ml. The higher circulating CFDNA clearance rate after standard therapy, the higher the rate of complete remission(CR) (P<0.05) and the longer overall survival(P<0.001). CONCLUSION: Elevated circulating cell-free DNA levels may be useful as a screening tool for lymphoma. Circulating CFDNA level may serve as a potential indicator for evaluation of the curative effect and prognosis.

[Genomic Instability in Acute Transformation of Chronic Myelogenous Leukemia].

Chronic myeloid leukemia (CML) is a myeloproliferative disorder, characterized by excessive proliferation of myeloid cells. CML patients in early phase [also known as chronic phase (CP)] usually respond to treatment with tyrosine kinase inhibitors (TKI), some patients respond initially to TKI, but later become resistant, then resulting in the transformation from CP to more advanced phase, which were subclassified as either accelerated phase or blastic phase. At present, the molecular mechanisms of CML have been not yet clear, and acute transformation has been not fully understood, studies have shown that genomic instability promotes the acute conversion of CML. This review discusses the molecular mechanisms leading to the transformation of CML, and some therapeutic approaches.

[Demethylation effect of inhibitor As2O3 on expression of SHP-1 and C-kit genes in leukemia HL-60 cells].

This study was aimed to investigate the expression level of SHP-1 and C-kit genes in acute leukemia HL-60 cells and effect of inhibitor As2O3 demethylation on SHP-1 and C-kit genes expression. RT-PCR was used to detect the expression level of SHP-1 and C-kit mRNA in drug-treated cell group and control group. The methylation specific PCR (MSP) was applied to measure the methylation status of SHP-1 gene in HL-60 cells. The results showed that after being treated with As2O3 the recovery of SHP-1 gene expression was observed in HL-60 cells in which SHP-1 mRNA originally did not expressed, meanwhile the expression level of C-kit mRNA in HL-60 cells with high expression decreased. When HL-60 cells were treated with As2O3 of 1.0, 2.5, 5.0 µmol/L, the demethylation effects was enhanced, the expression of SHP-1 mRNA displayed an ascending tendency, and expression of C-kit mRNA showed an descending tendency in dose-dependent manner (P < 0.05). It is concluded that the absence of SHP-1 mRNA expression in HL-60 cells and recovery of expression after treatment with As2O3 suggest the hypermethylation of SHP-1 gene related with pathogenesis of leukemia, and the abnormal increase of C-kit mRNA expression maybe exist in formation of leukemia. The effect of As2O3 on expression of SHP-1 and C-kit shows dose-dependency, the higher the As2O3 concentration, the higher the SHP-1 expression and the lower the C-kit expression, moreover, the effect of As2O3 shows time-dependency in specific concentration. The SHP-1 mRNA expression negatively relates with C-kit mRNA expression, suggesting that the decrease or absence of SHP-1 expression in leukemia cells weakens the negative regulation on C-kit signaling pathway, thus plays a role in the formation of leukemia.