Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).@*METHODS@#The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared.@*RESULTS@#In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×109/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×109/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage.@*CONCLUSION@#Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.

Analysis of Related Factors Affecting the Nosopoiesis of Childhood Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the related factors affecting the nosopoiesis of childhood acute leukemia from the perspective of indoor environmental exposure, behavior and lifestyle.@*METHODS@#The clinical data of 64 children with acute leukemia were retrospectively analyzed, and 50 healthy children were selected as the control group during the same period. The basic data of children, indoor environment, behavior and lifestyle of parents in 2 groups were recorded. Univariate and multivariate logistic regression analysis were used to analyze the related factors affecting the incidence of childhood acute leukemia, and the OR (95%CI) value was calculated.@*RESULTS@#The unvariate analysis showed that the daily wine-drinking rate of father and pesticide use rate in acute leukemia group were significantly higher than those in control group (P<0.05). Multivariate Logistic regression analysis showed that indoor ventilation during summer sleep of children (OR=0.35, 95%CI: 0.14-0.88) and contact with other children before 3 years old (OR=0.34, 95%CI: 0.18-0.65) were protective factors for provention of childhood acute leukemia (P<0.05). Mothers had a history of exposure to chemical substances (OR=3.68, 95%CI: 1.64-8.27), and children had a history of exposure to chemical substances (OR=3.84, 95%CI: 1.64-9.01), family had internal decoration history after child birth (OR = 1.38, 95%CI: 1.05-1.81) and family uses of pesticides (OR=2.17, 95%CI: 1.08-4.36), all these factors were independent risk factors for acute leukemia (P<0.05).@*CONCLUSION@#Indoor environmental exposure, behavior and lifestyle of children and parents may be closely related with the nosopoiesis of childhood acute leukemia.

Effect of Interferon Combined with Thalidomid on HEL Cell Apoptosis and JAK2V617F Mutation Gene Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of interferon-α2b combined with thalidomid(THD) on the proliferation and apoptosis of HEL cells, and expression of JAK2V617F-mutated gene.</p><p><b>METHODS</b>The cell survival rates were assayed by CCK-8 after HEL cells were treated by interferon-α2b, thalidomid and thalidomid combined with interferon-α2b for 24, 48 and 72 hours, while the apoptosis and expression of JAK2V617F mutation gene were detected by flow cytometry and fluorescence quantitative PCR respectively after treatmemt for 48 hours.</p><p><b>RESULTS</b>IFN-α2b combined with THD could more obviously inhibit the proliferation of HEL cells than IFN-α2b or THD alone for 24 and 48 and 72 hours, and the differences between groups were statistically significant(P<0.05). In addition, the apoptosis-inducing effect of IFN-α2b combined with THD on HEL cells was more obvious than that of IFN-α2b used alone, the differences was statistically significant(P<0.05). Although IFN-α2b combined with THD can decrease the JAK2V617F mutation gene expression more obviously than IFN-α2b alone,but the difference was no statistically significant (P>0.05). And the remaining groups showed statistically significance(P<0.05).</p><p><b>CONCLUSION</b>IFN-α2b combined with THD can obviously inhibit the proliferation and induce apoptosis of HEL cells more than that of IFN-α2b alone, but the effect of reducing JAK2V617F mutation gene expression is not different.</p>

IDH1 Gene Mutation and Its Clinical Significance in patients with Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis.</p><p><b>METHODS</b>Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed.</p><p><b>RESULTS</b>Among the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>The IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.</p>