Multicenter study of venetoclax-based combined regimen in treatment of adult acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.

Serum nuclear magnetic resonance-based metabolomics in patients with diffuse large B-cell lymphoma: a pilot study / 白血病·淋巴瘤

Objective To discover new biomarkers for diffuse large B-cell lymphoma (DLBCL) diagnosis and prognosis using nuclear magnetic resonance (NMR)-based serum metabolomics. Methods High-resolution serum 1H NMR spectra were collected from 7 DLBCL patients and 7 healthy controls. Spectra were processed using stoichiometry pattern-recognition methods [principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA)]. Results Significant difference (P <0.05) in 9 metabolites was observed between DLBCL and healthy control by OPLS-DA (variable interpretation rate R2Y ＝ 99.0 % and prediction rate Q2＝ 94.5 %). Compared with the healthy control group, higher levels of lactate (r ＝0.60, P<0.01), glycine (r ＝0.84, P<0.001), creatine (r ＝0.63, P<0.01), and choline (r ＝0.69, P< 0.01), lower levels of acetate (r＝ -0.88, P< 0.001), high-density lipoprotein (r＝ -0.77, P< 0.001), citrate (r ＝-0.82, P<0.001), glutamine (r ＝-0.53, P<0.05) and phosphocholine/glycerophosphocholine (r ＝-0.62, P<0.001) were detected in the serum samples of DLBCL. Conclusion The results of this study offer an evidence for significant changes between DLBCL patients and healthy people in serum metabolite profiles utilizing NMR-based serum metabolomics.

Inhibition effect of disulfiram combined with Cu on the growth of human Burkitt lymphoma cell xenografts in nude mice / 肿瘤研究与临床

Objective To investigate the effects of disulfiram (DS) combined with Cu on the human Burkitt lymphoma cell xenografts in nude mice.Methods Burkitt lymphoma xenograft was established by subcutaneous injection of Raji cell into nude mice after 2 Gy whole body X-irradiation (1×107 Raji cells were resuspended in 200 μl saline).18 bearing tumor mice were randomly divided into control group,DS group and DS/Cu group.During the experiment,the effects of DS/Cu on the nude mice with tumors were examined,including the tumor volumes,weights and the growth curves of xenograft tumor.Histopathological examination of tumor tissue was observed with optical microscape.The protein expression levels of p-JNK and c-jun were also detected by Western blot.Results Subsequent tumor size and weight in DS or DS/Cu-treated animals were (67.71±2.15) mm3,(33.35±7.74) mm3 and (43.35±4.22) mg,(18.05±2.88) mg.One-way ANOVA analysis indicated that the tumor size and weight in DS or DS/Cu-treated animals were reduced significantly relative to tumors in vehicle-treated animals (F =27.579,P =0.000;F =16.369,P =0.000).Furthermore,multiple comparisons revealed that the DS or DS/Cu-treated animals had significantly reduced tumor size and weight compared with control animals (all P ＜ 0.05).There were significant differences in tumor size and weight between DS or DS/Cu-treated animals (both P ＜ 0.05).Tumor inhibition rates in DS or DS/Cu group were 63.48 ％ and 80.24 ％,respectively.An increase of apoptosis changes in the xenograft tumor cells in DS or DS/Cu treated mice were more significant.Westem blot showed that the p-JNK and c-jun protein expressions in the tumors were improved after the DS or DS/Cu treatment,more obvious in DS/Cu treatment.Conclusion DS/Cu can inhibit the growth of xenografts,and one possible mechanism may involve the regulation of JNK signal pathway.

Clinical features and risk factors for infections in adult acute leukemia after chemotherapy / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical characteristics of infections in adult acute leukemia （AL）patients during chemotherapy in hospital, and identify the risk factors for infections.</p><p><b>METHODS</b>A retrospective study of patients with AL who underwent chemotherapy between July 2010 and Dec 2014 in the First Affiliated Hospital of Xiamen University was conducted. Clinical features and risk factors for infections were analyzed.</p><p><b>RESULTS</b>191 patients with AL received a total of 728 courses of chemotherapies. During these admissions, 385（52.9%) infections episodes occurred. The common infections sites were lower respiratory tract infection（36.3%，153/374）, bloodstream infection（17.1%, 64/374）, oral infection（13.6%，51/374）, and perianal infection（13.4%, 50/374）. 164 strains of pathogenic bacteria were detected. Gram- negative bacteria were recorded in 59.1% of documented pathogens, and Gram- positive bacteria were responsible for 32.9% of infections. Multivariate unconditioned logistic analysis of factors identified consistent independent risk factors for no completely remission（OR=0.142, P< 0.001）, duration of neutropenia longer than 7 days（OR=12.764, P<0.001）, general wards（OR=1.821, P< 0.001）, and hospitalization interval longer than 10 days（OR=0.720, P=0.039）.</p><p><b>CONCLUSION</b>Infections after chemotherapy for AL continues to be common. AL patients with induction chemotherapy or severe neutropenia faced an increased risk of infections by multivariate analysis. And patients with short-term stay or laminar flow wards seem to be less susceptible to infections.</p>

Molecular mechanisms of Survivin gene expression regulated by imatinib / 白血病·淋巴瘤

Objective To investigate the influences of imatinib on Survivin gene expression in bcr-abl-transformed leukemia cells.Methods Firstly,PCR and Western blot were carried out to detected Survivin expression with imatinib treatment in 32Dcl3 and 32D-bcr-abl cell lines.Then the luciferase reporter plasmids containing human Survivin promoter as well as its deletion and site-directed mutation were constructed to identify the essential responsive elements for suppressing Survivin promoter activity by imatinib.Chromatin immunoprecipitation was performed to confirm the binding of c-myc to Survivin promoter.10058-F4,a small molecule c-myc inhibitor,was used to disrupt c-myc activity and evaluate its anti-leukemic effect combined with imatinib.Results Both of mRNA and protein level of Survivin in bcr-abl-transformed cells were downregulated upon imatinib treatment.The decrease of Survivin expression was controlled at the transcriptional level through a mechanism in which imatinib repressed survivin promoter activity by disturbing the interaction between c-myc and E-box elements.Interruption of c-myc activity by 10058-F4 exerted an anti-leukemia effect with enhancing the sensibility of K562/G01 cells to imatinib.Conclusion Imatinib down-regulates Survivin expression through c-myc-mediated transcription and interference with c-myc might be a potential utility for treatment of imatinib resistant leukemia.