Clinical observation of venetoclax-based treatment regimens for acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

Efficacy analysis of decitabine monotherapy or combined with arsenic trioxide in treatment of myelodysplastic syndromes / 白血病·淋巴瘤

Objective To analyze the therapeutic effect and tolerability of decitabine monotherapy or combined with arsenic trioxide for the treatment of patients with myelodysplastic syndromes (MDS). Methods Clinical characteristics of 32 patients with primary MDS in North Hospital of Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University from January 2014 to April 2017 were retrospectively analyzed. The clinical data of these patients were collected, and the patients were followed up. Decitabine combined with arsenic trioxide was used in 23 cases, decitabine (20 mg·m-·2d-1) and arsenic trioxide (0.16 mg/kg) were administrated from day 1 to day 5 and was repeated every 4-6 weeks. For the remaining 9 cases, only decitabine was applied, decitabine(20 mg·m-2·d-1) was administrated from day 1 to day 5 and was repeated every 4-6 weeks. The clinicopathological characteristics and the effect of genetic mutations on the efficacy of treatment were investigated. Results Of the 32 patients with primary MDS, 18 were male and 14 were female. The patients were 17-72 years old with a median age of 56 years old. Genetic analysis revealed 10 cases with TP53 mutations, 8 cases with TET2 mutations, 4 cases with U2AF1 mutations, 3 cases with RUNX1 mutations, 3 cases with ASXL1 mutations, 2 cases with NRAS mutations, 2 cases with DNMT3A mutations and 1 case with JAK2 V617 mutation. The follow﹣up time was 2-23 months with a median follow﹣up time of 8 months. A total of 21 cases (65.6%) attained treatment response. Among them, there were 10 cases (31.3%) with complete remission (CR), 5 cases (15.6%) with bone marrow complete remission (MCR), and 6 cases (18.7%) with hematological improvement. There was no significant difference in the efficiency and CR rate between the combination group and the monotherapy group (P＝0.441, P＝0.681). Ten cases were found to have TP53 mutations, of which 7 cases had CR. Multivariate analysis demonstrated that TP53 mutation was an independent risk factor for CR (P＝ 0.037). All patients developed myelosuppression after treatment, of which 16 cases developed pulmonary infection. Conclusions Decitabine combined with arsenic trioxide in the treatment of MDS is effective and well tolerated. The therapeutic effects of decitabine monotherapy or decitabine combined with arsenic trioxide for treatment of patients with TP53 mutations are better than the average levels.

The clinical significance of serum neopterin and adenosine deaminase in patients with secondary hemophagocytic lymphohistiocytosis / 中华内科杂志

Objective To investigate the significance of plasma neopterin (Npt) and adenosine deaminase (ADA) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).Methods Serum specimens from 39 patients with newly diagnosed sHLH,10 sHLH patients who had achieved clinical remission after treatment,and 15 healthy controls were collected.Serum Npt level was detected by enzyme linked immunosorbent assay (ELISA) and ADA activity was tested by kinetic method.Results Npt and ADA values in sHLH group were significantly higher than those in control group [Npt:(164.6 ± 90.0) nmol/L vs (7.9 ± 3.6) nmol/L; ADA:(117.2 ± 70.2) U/L vs (11.6 ± 4.0) U/L; all P ＜ 0.001].Among the 10 sHLH patients who obtained effective clinical treatment,posttreatment levels of Npt and ADA were significantly lower than pretreatment data [Npt:(17.5 ± 10.9) nmol/L vs (170.6 ± 117.9) nmol/L ; ADA:(22.5 ± 15.5) U/L vs (98.8 ± 52.6) U/L; all P ＜ 0.05].The Npt level in sHLH patients was positively correlated with the levels of serum soluble interleukin-2 receptor (sCD25) and serum ferritin (r =0.526 and r =0.507) ; while ADA activity had linear relationship with the level of lactate dehydrogenase (r =0.646).Receiver operating characteristic (ROC) curve analysis showed that 148.1 nmol/L was the critical value of serum Npt for the diagnosis of lymphoma associated hemophagocytic syndrome (LAHS) and the sensitivity and specificity were 70.0％ and 78.9％,respectively.As to ADA,103.1 U/L was the critical value for the diagnosis of LAHS and the sensitivity and specificity were 75.0％ and 84.2％,respectively.The sensitivity and specificity of combined parameters of Npt and ADA were 90.0％ and 94.7％,respectively.Conclusions It is concluded that Npt and ADA have great importance in the diagnosis and evaluation of therapeutic effect in patients with sHLH.Npt and ADA provide potential evidence to diagnose patients who are suspected with LAHS.

Influence of ceftriaxone and imipenem to sepsis in the rat intestinal flora and bacterial drug resistance / 中国生化药物杂志

Objective To study the influence of ceftriaxone and imipenem to sepsis in the rat intestinal flora and bacterial drug resistance.Methods 8 rats were randomly included in normal control group from 48 healthy SD,and the rest of them were built the endotoxin sepsis model using 15 mg/kg intraperitoneal injection of endotoxin.According to whether to apply antibiotics and application deadlines in 24 h after modeling,40 rats were randomly subdivided into sepsis without treatment group,sepsis ceftriaxone 3 d group,sepsis ceftriaxone 7 d group,sepsis imipenem 3 d group and sepsis imipenem 7 d group(n=8).During ceftriaxone and imipenem injection treatment,in the corresponding time,colon contents were taken for enterobacteriaceae,enterococcus strains of quantitative culture and bacteria and fungi identification. Results After treatment with antibiotics,the number of rat intestinal bacteria decreased significantly(P<0.05).Ceftriaxone selected pseudomonas aeruginosa and enterobacter cloacae,while imipenem selected klebsiella pneumoniae, proteus and excrement enterococcus conditional pathogenic bacteria.All showed the inclination resistance. Conclusion Ceftriaxone and imipenem antibiotics could decrease the original bacteria number,so pseudomonas aeruginosa and excrement enterococcus conditional pathogenic bacteria could become advantage bacterium group,causing intestinal micro ecological environment disruption.

Analysis of ND4 gene mutations in acute myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations.</p><p><b>METHODS</b>Using PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features.</p><p><b>RESULTS</b>There were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05).</p><p><b>CONCLUSION</b>It was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.</p>

Clinical manifestation of the SRSF2 gene mutation in Chinese patients with chronic myelomonocytic leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spliceosome mutations have been recently identified and associated with hematological malignancies. SRSF2, one of components of the splicing machinery, has a high mutation frequency during chronic myelomonocytic leukemia, according to previous reports. However, the relevance of this finding in Chinese populations remains unknown.</p><p><b>METHODS</b>We recruited 50 Chinese patients with chronic myelomonocytic leukemia to analyze the state of SRSF2 and to assess the corresponding clinical features by polymerase chain reaction followed by direct sequencing.</p><p><b>RESULTS</b>Ten of 50 patients (20%) harbored SRSF2 mutations, including five P95R, two 95H, and three P95L point mutations. The patient group was older than the wild type group (P < 0.01). No significant statistical differences were observed with regard to the other clinical characteristics (sex, peripheral blood count, serum lactate dehydrogenase, karyotype, World Health Organization classification, etc.) between these two groups. Two of the patients showed an early evolution to acute myeloid leukemia.</p><p><b>CONCLUSIONS</b>SRSF2 mutations are frequent in chronic myelomonocytic leukemia patients, but show a relatively lower incidence in Chinese patients. Moreover, the mutation can be related to old age and an unfavorable prognosis. Our results provide valuable insights for the development of a diagnostic marker, or for the identification of a therapeutic target for chronic myelomonocytic leukemia.</p>

Abnormalities of chromosome 17 in myeloid malignancies with complex chromosomal abnormalities / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of the abnormalities of chromosome 17 in myeloid malignancies with complex chromosomal abnormalities (CCAs).</p><p><b>METHODS</b>Abnormalities of chromosome 17 were analyzed in 73 patients with myeloid malignancies with CCAs showed by R banding and conventional karyotyping, including 21 acute myeloid leukemia (AML), 36 chronic myeloid leukemia (CML) and 16 myelodysplastic syndrome (MDS). All CCAs were further analyzed by multiplex fluorescence in situ hybridization (M-FISH).</p><p><b>RESULTS</b>Among the 73 myeloid malignancies with CCAs, chromosome 17 was the most frequently involved chromosome. It was found in 46.5% (34/73) of all cases, including 12 AML, 13 CML in blast crisis (BC) and 9 MDS. However, it was not found in the 9 CML cases in chronic phase (CP). The majority of changes were structural rearrangements which were identified in 43.8%(32/73)of all cases, among them the frequency was 52.4% (11/21), 33.3% (12/36) and 56.3% (9/16) in AML, CML and MDS, respectively. Numerical abnormalities were detected in 15.1% (11/73) cases, all were monosomy 17, and the frequency was 25.0% (3/12), 38.5% (5/13) and 33.3% (3/9) in AML, CML and MDS, respectively. Both numerical and structural abnormalities of chromosome 17 were found in 9 cases. Unbalanced translocations involving chromosome 17 were much more frequent than balanced ones. In the 3 groups, 16, 15 and 8 unbalanced translocations were found respectively. Only two kind of balanced translocations including t(15;17) in AML and t(15;17;22) in CML were found. All chromosomes were involved except chromosomes 5, 6 and 22 as partner chromosomes, the most common one was chromosome 15 (8.2%), followed by chromosome 2 (5.4%). Five of the 6 cases with translocation of chromosomes 15 and 17 were acute promyelocytic leukemia, the other case was CML-BC.</p><p><b>CONCLUSION</b>Abnormalities of chromosome 17 were the most frequently involved chromosomal aberrations in myeloid malignancies, and structural rearrangements were more common. All the numerical abnormalities were monosomy 17, unbalanced translocations were much more frequent than balanced ones.</p>

Expression of CD38 in T cells of chronic lymphocytic leukemia / 中华检验医学杂志

Objective To explore the CD38 expression in T-cens(CD38-T)of chronic lymphocytic leukemia(CLL).Methods Multi-parameter flow cytometry was used to detect the expression of CD38,ZAP-70 and CD4/CD8 in 83 CLL patients.Results CD38 was positively expressed in 49.4%(41/83)T-cells(CD38-T)and 50.6%(42/83)tumor cells(CD38-B)of all CLL patients.The expression of the CD38-T was highly correlated with CD38-B(r=0.553,P＜0.01).ZAP-70+CD38+-T and ZAP-70-CD38-T constituted 67.5%(56/83)of CLL patients.There was significant correlation between CD38-T and ZAP-70 (r=0.349,P＜0.01).There was 33.3%(14/42)patients with CD38-T in Binet A patients,and 65.9% (27/41)in Binet B+C patients.There was also significant correlation between CD38-T and Binet B+C(r=0.312,P＜0.05),and CD4/CD8(r=0.453,P＜0.05).Conclusions Aberrant expression of CD38 in T-cells might be of prognostic relevance in CLL Most of the patients with high level CD38-T expression are accompanied with disorder or imbalance of immune function.CD38 expression in T cells might be a new prognostic factor in CLL.