Leukemia/Lymphoma -Pubmed

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First-line treatment failure in childhood acute lymphoblastic leukemia: The polish pediatric leukemia and lymphoma study group experience.

Medicine (Baltimore). 2020 Feb;99(7):e19241

Authors: Zawitkowska J, Lejman M, Drabko K, Zaucha-Prażmo A, Płonowski M, Bulsa J, Romiszewski M, Mizia-Malarz A, Kołtan A, Derwich K, Karolczyk G, Ociepa T, Ćwiklińska M, Trelińska J, Owoc-Lempach J, Niedźwiecki M, Kiermasz A, Kowalczyk J

Abstract
The aim of this study was to evaluate the risk factors of relapse and treatment-related deaths in acute lymphoblastic leukemia (ALL) in children residing in Poland.A total of 1872 patients with newly diagnosed ALL, treated according to the ALL IC-BFM 2002 protocol in 14 Polish pediatric hematology centers from 2002 to 2012 were included in the study. Three-hundred eighty-four patients experienced treatment failure. The last follow-up was 31 December, 2016.Univariate analysis identified factors in each risk group that were significantly different between children whose treatment failed and those who remained in the first remission. Multivariate analysis demonstrated that only the age of 10 years or over at primary diagnosis in the high-risk group was an adverse prognostic factor. To facilitate the analysis, patients were divided into three groups: relapsed children who survived; relapsed children who died; children without relapse who died due to toxicity.Our analysis showed that age older than 10 years is a particular risk factor for the failure of first-line of treatment, both in terms of relapse and treatment-related mortality.

PMID: 32049864 [PubMed - indexed for MEDLINE]

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Clinical efficacy and safety of imatinib treatment in children and adolescents with chronic myeloid leukemia: A single-center experience in China.

Medicine (Baltimore). 2020 Feb;99(7):e19150

Authors: Deng M, Guan X, Wen X, Xiao J, An X, Yu J

Abstract
Chronic myeloid leukemia (CML) is relatively rare in childhood and few studies have reported the clinical use of imatinib (IM) in pediatric CML. In this study, we evaluated the efficacy and tolerability of IM in children and adolescents with CML.We investigated 21 patients under 18 years of age with newly diagnosed CML and treated with IM in Children's Hospital of Chongqing Medical University between May 2014 and February 2018. The disease was staged according to the European LeukemiaNet criteria and the IM dose was determined based on the disease stage. Cumulative responses and survival probabilities were estimated according to the Kaplan-Meier method.The estimated complete hematologic response rate of chronic phase-chronic myeloid leukemia (CML-CP) was 89.5% at 3 months. The complete cytogenetic response rates increased with time, reaching 47.4%, 73.7%, and 80.3% at 6, 12, and 24 months, respectively. The cumulative major molecular response rates were 42.1% and 76.3% at 12 and 24 months, respectively. With a median follow-up time of 33.8 months (range, 3.2-61.7 months), the estimated 2-year overall survival (OS) rate for CML was 95.2% (95% confidence interval [CI], 70.7%-99.3%). None of the CML-CP patients progressed to the accelerated phase or had a blast crisis. The 2-year OS and progression-free survival rates for the CML-CP cohort were both 100%, while the estimated 2-year event-free survival rate was 68% (95% CI, 42.1%-84.2%). None of the patients in this group had treatment-related deaths or IM discontinuation due to drug toxicities, and only 1 patient had a grade III-IV nonhematologic adverse event. Overall, anemia was the most common adverse effect and 42.9% of patients had a decrease in bone mineral density.IM was effective and the adverse effects were well-tolerated throughout the follow-up period in Chinese CML patients under 18 years of age.

PMID: 32049841 [PubMed - indexed for MEDLINE]

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Computed tomography texture analysis for assessment of chemotherapy response of Hodgkin lymphoma.

Medicine (Baltimore). 2020 Feb;99(7):e19146

Authors: Reinert CP, Wanek L, Bösmüller H, Federmann B, Fritz J, Sökler M, Horger M

Abstract
The aim of this study was to test the hypothesis that computed tomography texture analysis (CTTA) is accurate for response assessment of Hodgkin lymphoma (HL).A total of 100 patients with HL were identified. CTTA in baseline and interim staging was performed generating volume of interests in lymphoma tissue from which CTTA features including 1st, 2nd, and higher order textural features were extracted. Baseline and interim 2-deoxy-fluor-glucose positron emission tomography results were used to determine therapy response and compared to CTTA in terms of patient outcome.At interim, 1st-order features yielded a significant drop (e.g., entropy of heterogeneity, P = .01) or a significant rise (deviation, P < .001), whereas 2nd and higher order features decreased (e.g., entropy of co-occurrence matrix, P < .001). Patients achieving complete remission at end of treatment had a significantly lower entropy of heterogeneity at baseline and interim compared to patients achieving partial remission (P < .05).CT textural features change in parallel to metabolic therapy response, and are therefore a feasible diagnostic tool for a more accurate response assessment of HL.

PMID: 32049838 [PubMed - indexed for MEDLINE]

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[Research Advance on Classic Wnt Pathway in Chronic Myelogenous Leukemia--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):350-353

Authors: Cao ZR, Chen XP, Hu J

Abstract
Abstract  Chronic myelogenous leukemia (CML) is a hematological malignancy that seriously threatens the lives of patients. It was found that there are abnormal classic Wnt pathway, that is, Wnt/β-catenin signaling pathways in CML cells, moreover, Wnt/β-catenin signaling pathway is involved in the growth and proliferation of CML cells, and closely relates with the self-renewal ability of CML leukemic stem cells. This review summarizes the recent studies on the relationship between Wnt/β-catenin signaling pathway and CML, and the researches on the targeting inhibition of Wnt/β-catenin signaling pathway in CML treatment, thus to provide new ideas for the treatment of CML.

PMID: 32027302 [PubMed - indexed for MEDLINE]

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[Reaserch Advance on Treatment Strategies for Relapsed/Refractory Hodgkin's Lymphoma--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):343-349

Authors: Jin DC, Zhao L

Abstract
Abstract  Although the majority of patients with Hodgkin's lymphoma (HL) can be cured with upfront treatment, but a fraction of patients with advanced disease will experience refractory or recurrence leading to poor prognosis. How to treat these patients is the focus of current research. High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (HDCT/auto-HSCT) is the standard salvage approach for patients with HL who have relapsed/refractory disease after frontline chemotherapy. In recent years, salvage therapy incorporating newer drugs, such as targeted drugs Brentuximab vedotin (BV), checkpoint inhibitors Nivolumab and Pembrolizumab have shown some efficacy in early clinical trials. In addition, Ibrutinib, Everolimus and other drugs have also shown a promising perspective. In this review, the advances in the therapy strategies for relapsed/refractory HL are discussed and summarized.

PMID: 32027301 [PubMed - indexed for MEDLINE]

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[Reaserch Advance on Bruton Tyrosine Kinase Inhibitors in the Treatment of B-Cell Tumors--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):333-338

Authors: Ji TT, Chen QN, Tao SD, Yu L

Abstract
Abstract  In recent years, development of the targeted drugs according to the biological characteristics of tumors have provided more treatment options for tumor patients. It was found that the overactivation or abnormality of B cell receptor (BCR) signal pathway closely related to the occurrence and development of various B cell tumors, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a key kinase in the BCR pathway, BTK inhibitors have obvious anti-tumor effect when its activity is being inhibitered. Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin's lymphoma (NHL). However, its side effects and drug-resistance also gradually emerged, effective drug combination therapy has shown a certain clinical activity. This reviews summarizes briefly the mechanism and status of BTK inhibitors in the treatment of various B-cell tumors.

PMID: 32027299 [PubMed - indexed for MEDLINE]

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[Research Advances on Abnormal Secretion and Function Abnormality of Exosomes Derived from Lymphoma Cells Caused by Latent EB Virus--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):325-328

Authors: Huang HB, Shen JZ

Abstract
Abstract  The Latent infection cansed by Epstein-Barr virus (EBV) closely relates with the occurrence and development of several kinds of lymphoma. Exosome (EXO) is functional bilayer membrane structural corpuscles which are secreted by cells contain proteins, lipids and nucleic acids. In recent years, researches showed that EXO play an important role in the occurrence and development of tumors. Therefore, the resenrches which compare the differences in quantity and contents of EXO secreted by cells between EBV negative lymphoma and EBV positive lymphoma and the clarify the influence of EXO on biological behaviors of lymphoma cells and immune cells have the important, significance for understanding the mechanisms related with effect of latent EBV on the occurrence and development of lymphoma by exosome pathway. This review focuses on research progress about the effect of latent EBV on amounts, contents and functions of EXO secreted by lymphoma cells.

PMID: 32027297 [PubMed - indexed for MEDLINE]

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[Effect of B4GALT1 on Proliferation of Its Co-cultured Human Acute Myeloid Leukemia Cell Line in Bone Marrow Stromal Cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):283-289

Authors: Pang XC, Li HJ, Wang Y, Guan F, Li X

Abstract
OBJECTIVE: To investigate the effect of bone marrow stromal cell glycosyltransferase B4GALT1 expression on hematopoietic cell proliferation and its upstream regulation mechanism.
METHODS: B4GALT1 was overexpressed in human bone marrow stromal cell line HS5, which was then co-cultured with acute myeloid leukemia cell line KG1a. And its effect on hematopoietic cell proliferation was detected by flow cytometry. Dual luciferase reporter assay, real-time PCR and Western blot were used to predict and validate upstream transcription factors that regulate stromal cell B4GALT1 expression.
RESULTS: Overexpression of B4GALT1 in HS5 significantly promoted the proliferation of KG1a in the co-culture system. B4GALT1 expression in stromal cells positively correlated with upstream c-Jun expression, which was verified by JNK/c-Jun inhibitors.
CONCLUSION: The differential expression of glycosyltransferases and their corresponding glycosylation in the hematopoietic microenvironment play an important role.

PMID: 32027290 [PubMed - indexed for MEDLINE]

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[Clinical Significance of Minimal Residual Disease Monitoring by Multi-parameter Flow Cytometry before Allogeneic Hematopoietic Stem Cell Transplantation for Prognosis of Acute Leukemia Patients].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):262-266

Authors: Liu C, Liu L, Chen JB, Tang XQ, Xiao Q, Zhang HB, Wang JY, Wang L, Zhan Q, Wang X

Abstract
OBJECTIVE: To investigate the clinical significance of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia.
METHODS: 81 cases of patients with AL treated with allo-HSCT in Department of Hematology, the First Affiliated Hospital of Chongqing Medical University form July 2015 to July 2018 was selected and retorspectively analyed. of which 79 patients were in CR and two patients were in non-CR. The CR group was further divided into two groups of MRD+ and MRD- based on the MRD level prior to HSCT.
RESULTS: Among 81 patients, there were statistically significant differences in the three-year overall survival(OS) (CR 82.2%: NCR 0%), cumulative relapse incidence(RI) (CR 17.7%; NCR 100%) and leukemia-free survival rate(LFS) (CR 42.3%: NCR 0%) between CR and NCR group(P<0.05). Among 79 CR patients, MRD was negative in 30 patients while positive in 49 patients, there was significant differences in the three-year overall survival between MRD- and MRD+ group. The results of univariate analysis showed that the MRD+ group showed lower LFS compared with that of MRD- group (10.5% vs 36.2%)(P<0.001,95%CI).
CONCLUSION: MRD- patients shows longer LFS as compared with that of MRD+ patients, therefore, MRD monitoring by MFC before allo-HSCT is very important for the prognosis of the AL patients.

PMID: 32027287 [PubMed - indexed for MEDLINE]

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[Analysis of Decitabine Therapeutic Effeicacy for Patients with Relapsed MDS/AML and High-Risk AML Patients after HSCT].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):248-254

Authors: Wang QY, Liang ZY, Dong YJ, Yin Y, Wang Q, Liu W, Xu WL, Li Y, Ren HY

Abstract
OBJECTIVE: To investigate the therapeutic efficacy of using decitabine as maintenance therapy for patients with relapsed MDS/AML and as prophylactic therapy for patients with high-risk AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS: Clinical data of 10 patients with MDS/AML from November 2016 to May 2018 were analyzed retrospectively. Among 10 patients there were 4 cases of AML, 2 cases of MDS, and 4 cases of AML transformed from MDS (t-AML). The 10 patients were devided into 2 groups: the relapsed group (n=8) and the prophylactic group (n=2). In relapsed group the decitabine was used as maintenance therapy after achieved complete remission (CR) with decitabine chemotherapy. In prophylactic group the decitabine was used as prophylactic therapy if the patients didn't appear the symptom of graft-versus- host-disease (GVHD) during 30 to 45 d after allo-HSCT. Eight patients received G-CSF-mobilized donor lymphocyte infusion (DLI). The dosage of decitabine for maintenance therapy and prophylactic therapy was 5 mg/m2 for 7 to 10 days every 4 to 6 weeks, as 1 cycle, amount to 3 to 7 cycles. The dosage was adjusted by the endurance of patients.
RESULTS: Until Nov 30, 2018, 7 out of 10 patients survived. The average survival time was 15.5±1.9 months. 1-year OS rate was 64.0%. Six patients appeared aGVHD, and four patients appeared cGVHD.
CONCLUSION: The usage of decitabine combined with DLI in patients with relapsed MDS/AML and high-risk AML after allo-HSCT can prolong lives of patients, reduce relapsed rate, and provide the probability for long time survival.

PMID: 32027285 [PubMed - indexed for MEDLINE]

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[Therapeatic Efficacy of Decitabine on Low and Moderate-Risk MDS Patients and the Prognostic Factors].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):214-217

Authors: Shu HE, Fang T

Abstract
OBJECTIVE: To investigate the efficacy of decitabine in the treatment of patients with low-risk and moderate-risk myelodysplastic syndrome (MDS) and to analyze the prognostic factors.
METHODS: A retrospective study was conducted on 47 patients with low and moderate risk MDS treated with decitabine in our hospital. The course of treatment was 20 mg/(m2·d)×5 d injected subcutaneously for 28 d as a course of treatment. After 3 to 4 courses of treatment, the therapeutic response and survival prognostic factors of patients were evaluated.
RESULTS: According to the revised IWG standard, 18 patients (38.3%) achieved CR, 13 patients (27.7%) achieved PR, 7 patients (14.9%) showed hematological improvement, 7 patients (14.9%) died of pulmonary infection or myelosuppression, 2 patients transformed into acute myeloid leukemia. The median survival time of MDS patients was 26 months. The overall effective rate of decitabine regimen was 80.9% (38/47). The independent poor prognostic factors for survival were high IPSS grade, long course of MDS, early treatment for MDS, and elder.
CONCLUSION: The long-term efficacy of decitabine in the treatment of low and moderate-risk MDS is definite. The clinical factors before treatment may predict the efficacy of decitabine in the treatment of MDS.

PMID: 32027279 [PubMed - indexed for MEDLINE]

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[Analysis of RUNX1 Gene Mutation in Patients with Myelodysplastic Syndrome].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):202-208

Authors: Cai XH, Chen MY, Chao HY, Jiang NK, Lu XZ, Han WM, Qin W, Jia ZX

Abstract
OBJECTIVE: To investigate the mutation of RUNX1 gene in patients with myelodysplastic syndrome (MDS) and its correlation with other gene mutations and some clinical parameters.
METHODS: The mutations of RUNX1, DNMT3A, TET2, IDH1/2, NPM1, FLT3-ITD and C-KIT in 170 patients with MDS were detected by direct and indirect sequencing of genomic DNA-PCR amplification products.
RESULTS: The RUNX1 mutation was found in 23 patients (13.5 %, 23/170). Among the 170 patients, other most frequent mutation was TET2 (11.2%, 19/170), followed by mutations in DNMT3A (9.4%, 16/170), NPM1 (8.2%, 14/170), IDH2 (4.1%, 7/170)、FLT3-ITD (2.9%, 5/170), IDH1 (1.7%, 3/170) and c-KIT (0.58%, 1/170). The most common coexisting mutations were TET2 (5/23). The RUNX1-mutated group showed significantly higher leukocyte levels, higher percentages of blast cells, higher incidences of leukemia transformation and lower platelet counts in comparison with RUNX1 non-mutation group (P<0.05). whereas there were no statistically significant difference in age, MDS subtype, karyotype and hemoglobin level between 2 groups (P>0.05). Seventeen patients harboring RUNX1 mutations were followed up and almost 47.05% (8/17) of the patients progressed into acute myeloid leukemia (AML). The rates of transformation into AML in ASXL1-mutation group was significantly higher than that in ASXLL- non-mutation group (47.05% vs 11.7%) (P=0.001).
CONCLUSION: The incidence of RUNX1 mutation is high in MDS patients. The RUNX1-mutated patients have higher leukocyte level, higher percentages of blast cells, higher incidences of leukemia transformation and lower platelet count.

PMID: 32027277 [PubMed - indexed for MEDLINE]

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[Expression and Clinical Significance of MicroRNA-195 in Patients with Diffuse Large B Cell Lymphoma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):160-164

Authors: Liu RD, Zhuang W, Qi JD, Li CC

Abstract
OBJECTIVE: To investigate the expression and clinical significance of microRNA-195 in patients with diffuse large B cell lymphoma(DLBCL).
METHODS: Sixty patients with DLBCL were selected from nearly four years in our hospital, and at the same time 30 healthy people with physical examination of the same period and with the same age in our hospital were choosed as control group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the miR-195 expression of the patients and controls, the relationship between miR-195 expression and clinicopathological characteristics of DLBCL and survival time of patients was analyzed.
RESULTS: The expression level of miR-195 in DLBCL patients was significantly lower than that in the controls (P<0.001). The expression level of miR-195 closely related with tumor diameter, IPI score and Ann Arbor stage of patients with DLBCL. Overall survival(OS) time of DLBCL patients with highly expressed miR-195 was significantly longer than that of patients with low expression (P<0.001).
CONCLUSION: miR-195 expression decrease in DLBCL patients, and miR-195 closely relates with tumor characteristics of patients with DLBCL. DLBCL patients with higher expression of miR-195 show longer overall survival time.

PMID: 32027270 [PubMed - indexed for MEDLINE]

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[Value of Red Blood Cell Distribution Width and Fibrinogen Level for Evaluation of the Therapeutic Efficacy and Prognosis in Patients with Diffuse Large B-Cell Lymphoma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):153-159

Authors: Wang X, Wu CY, Zeng PY, Li LL, Ma CC, Xiang X, Li YQ, Chai Y

Abstract
OBJECTIVE: To investigate the value of red blood cell distribution width (RDW) and fibrinogen (Fib) level for the evaluation of therapeutic efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).
METHODS: The relationship between RDW/Fib at initial diagnosis and efficacy and the clinical outcome was retro-spectively analyzed based on the study of 105 patients with DLBCL. The patients were divided into two groups: low RDW group (≤15%) and high RDW group (>15%), low Fib group (Fib≤4 g/L) and high Fib group (Fib>4 g/L) according to the normal values of RDW and Fib. Therapeutic efficacy, overall survival (OS) time and progression free survival (PFS) time were compared between two groups. The correlation between each factors and efficacy, prognosis was analyzed by univariate and multivariate regression.
RESULTS: The therapeutic efficacy (P<0.001), OS time(P=0.004), and PFS time(P=0.007) were poorer in the high RDW group as compared with the low RDW group. The efficacy (P=0.015) and PFS time(P=0.04) were poorer in the high Fib group as compared with the low Fib group. Multivariate analysis showed that high RDW was the independent risk factor for efficacy of DLBCL patients (OR=3.394, 95% CI 1.093-10.539, P=0.035).
CONCLUSION: High RDW and high Fib associate with poor efficacy in DLBCL patients.

PMID: 32027269 [PubMed - indexed for MEDLINE]

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[Mechanism of Sorafenib and Decitabine Inducing Apoptosis of Diffuse Large B-Cell Lymphoma Cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):146-152

Authors: Zhou Y, Wang X, An YH, Sun WDBMCBAPC, Tong XM

Abstract
OBJECTIVE: To investigate the effect of sorafenib combined with decitabine on the viability and apoptosis of diffuse large B-cell lymphoma cell line OCI-LY1 and its mechanism.
METHODS: Sorafenib at 1.5μmol/L or decitabine at 25μmol/L was used to treat the cells alone or in combination. The viability of OCI-LY1 cells was detected by CCK8 assay; the PI positive cells were observed by fluorescence microscopy; the cell proliferation and ROS levels were measured by flow cytometry; The expression levels of proteins related to apoptosis were detected by Western blot.
RESULTS: Compared with the control group, treatment with sorafenib and decitabine alone or in combination inhibited the cell proliferation, activated ROS formation and induced apoptosis finally. Sorafenib in combination with decitabine produced a synergistic effect. Western blot analysis showed that sorafenib combined with decitabine significantly up-regulated the levels of Bax/Bcl-2, P53, C-Caspase3 and C-PARP and activated apoptosis by inhibiting PI3K-AKT pathway.
CONCLUSION: Sorafenib combined with decitabine induces the apoptosis of diffuse large B-cell lymphoma cell line OCI-LY1 by inhibiting PI3K-AKT pathway and activating P53.

PMID: 32027268 [PubMed - indexed for MEDLINE]

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[Analysis of the Relationship between Cytogenetic Changes and Course Evolution of Patients with CML during TKI Treatment].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):136-140

Authors: Wang K, Liu T, Dai J, Pang YX, Wang Q

Abstract
OBJECTIVE: To analyze the relationship between cytogenetic changes and the progression in the patients with chronic myeloid leukemia (CML) during the treatment with tyrosine kinase inhibitor (TKI).
METHODS: The chromosome G banding of 150 patients with CML treated in our hospital, was carried out to analyze the karyotype by the 24 h short-term culture or direct method of bone marrow cells, and the point mutation of the ABL kinase area was detected, the relationship between cytogenetic changes and the evolution of the disease course was analyzed.
RESULTS: The indirect fluorescence in situ hybridization showed that the BCR-ABL fusion gene of 150 patients was positive, out of which 142 cases showed positive Philadelphia (Ph) (94.67%), 8 cases with Ph negative (5.33%). Among 142 cases with Ph positive on the first diagnosis, and 14 cases (9.86%) with additional chromosome abnormality (9.86%), 4 cases (2.82%) with mutation translocation with 124 cases (87.32%), standard translocation t (9; 22) (q34; Q11) were found. Out of the 14 patients with additional chromosomal abnormalities, 8 cases with "main pathmay" abnormalities, 2 case with -Y abnormalities, and 4 cases with "secondary pathway" abnormalities were observed. During TKI treatment, additional chromosomal abnormalities were found in 46 patients with standard translocation and abnormal number of chromosomes, and the incidence of disease progression and point mutation were higher (P<0.05). Compared with patients with the standard translocation, the disease-free survival rate of the patients diagnosed as CML at 1st visit and with additional chromosome abnormality was significantly decreased (P<0.05), but the overall survival rate showed no significantly different (P>0.05). Compared with patients without additional cvtogenetic aberrations, the disease free and overall survival rate of the patients with additional cytogenetic aberrations during the TKI treatment of CML in chronic phase were significantly decreased (P<0.05).
CONCLUSION: Some CML patients may have additional chromosomal abnormalities during the onset and development of the disease, and these patients are at higher risk of disease progression.

PMID: 32027266 [PubMed - indexed for MEDLINE]

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[Expression Level of TGFβ1 and VEGF Gene in Acute Myeloid Patients and Its Clinical Prognostic Value].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):130-135

Authors: Chen WT, Yao HX, Wu CM, Fu XJ, Huang ZQ

Abstract
OBJECTIVE: To study the expression level of TGFβ1 and VEGF gene in patients with acute myeloid leukemia (AML) and its clinical prognostic value.
METHODS: Seventy-eight AML patients treated in our hospital from July 2016 to September 2018 were selected. After isolation of bone marrow mononuclear cells from the patients, the levels of TGFβ1 and VEGF genes were detected by RT-PCR, and the correlation of TGFβ1 with VEGF genes and clinical characteristics of AML patients was analyzed. OS and EFS of the patients were evaluated by Kaplan-Meier, and Cox risk ratio model was used to analyze the prognostic risk factors of AML patients.
RESULTS: The relative expression level of TGFβ1 gene in AML patients was 0.32±0.04, which was significantly lower than that in control group (P<005). The relative expression level of vascular endothelial growth factor(VEGF) gene in the patients was 2.65±0.15, which was significantly higher than that in the control group (P<0.05). The levels of TGFβ1 and VEGF genes significantly correlated with leukocyte count, hemoglobin, platelet and peripheral blast levels in AML patients (P<0.05). The level of TGFβ1 in AML patients with complete remission was higher than that in patients with partial remission or non-remission (P<0.05). The level of TGFβ1 in AML patients with partial remission was significantly higher than that in patients with non-remission (P<0.05). The level of VEGF in AML patients with complete remission was lower than at in patients with partial remission or non-remission (P<0.05). The level of VEGF in AML patients with partial remission was significantly lower than that in patients with non-remission (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in AML patients with high expression of TGFβ1 were better than those in patients with low expression of TGFβ1 (P<0.05), OS and DFS in AML patients with low expression of VEGF were better than those in patients with high expression of VEGF (P<0.05). Multivariate Cox regression analysis showed that platelet, TGFβ1 and VEGF gene were independent influencing factors of OS (P<0.05). Leukocyte, TGFβ1 and VEGF gene were independent influencing factors of DFS (P<0.05).
CONCLUSION: Decreased expression of TGFβ1 and increased expression of VEGF gene in AML patients closely relate to the poor prognosis of AML patients, which can provide reference for improving clinical efficacy of AML patients.

PMID: 32027265 [PubMed - indexed for MEDLINE]

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[Relation of ASXL2 Gene Mutation with Clinical Characteristics, Prognosis and C-KIT Gene Mutation in AML Patients with AML1- ETO Fusion Gene].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):125-129

Authors: Cui P, Xu D, Xing T, Ren GH, Ma SM

Abstract
OBJECTIVE: To analyze relation of ASXL2 gene mutation with the clinical characteristics, prognosis and C-KIT gene mutation in acute myeloid leukemia (AML) patients with AML1-ETO fusion gene.
METHODS: The clinical data of 63 primary AML patients with AML1-ETO fusion gene were collected and retrospectively analyzed. The mutation of ASXL2 gene was directly sequenced by PCR. The clinical characteristics, C-KIT mutation rate and prognosis were compared between the patients with ASXL2 gene mutation (group A) and non-mutation (group B).
RESULTS: Among 63 patients, 8 (12.70%) cases of ASXL2 mutation gene was detected. Hemoglobin level in peripheral blood of patients in group A was significantly lower than that in group B (P<0.01). There was no significant difference in sex, ages proportion of bone marrow blasts, lymph node enlargement, peripheral blood leukocytes count and platelets between the two groups (P>0.05). The infiltration of central nervous system, liver and spleen was not found in both groups. The expression of CD33 in group A was significantly lower than that in group B (P<0.05), but the results of other immunophenotype analysis were not significantly different between the two groups (P>0.05). The remission rate and median survival time were not significantly different between two groups (P>0.05). The detection rate of C-KIT gene mutation were not significantly different between group A and group B (P>0.05).
CONCLUSION: Among AML patients with AML1-ETO fusion gene, ASXL2 gene mutation accounts for a certain ratio, and the peripheral blood hemoglobin concentration and CD33 expression in these patients are often low. At the same time, ASXL2 gene mutation may not be closely related with C-KIT gene mutation.

PMID: 32027264 [PubMed - indexed for MEDLINE]

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[Expression of MiR-429 in Patients with Acute Lymphoblastic Leukemia and Its Prognostic Value].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):119-124

Authors: Zhang LC, Zhong C, Ma YJ, Liu M, Nong WX

Abstract
OBJECTIVE: To analyze the expression level of miR-429 in patients with acute lymphoblastic leukemia(ALL) and its clinical prognostic value.
METHODS: One hundred and Twenty-six patients with ALL treated in our hospital from April 2016 to February 2018 were selected, and 100 healthy persons in the same period were selected as control group. Bone marrow mononuclear cells were collected. The expression level of miR-429 in bone marrow mononuclear cells was detected by RT-PCR, and the correlation of miR-429 expression with clinical characteristics and therapeutic efficacy was analyzed. Kaplan-Meier method and multi-factorial Cox regression model were used to analyze the correlation between the level of microRNA-429 and the prognosis of ALL patients.
RESULTS: The relative level of miR-429 in ALL patients was 2.47±0.07, which was signifi-cantly higher than that in control group (P<0.05). The level of miR-429 significantly correlated with the leucocyte level(r=0.994), LDH(r=0.992), the ratio of bone marrow primordial cells(r=0.995) and risk grade of ALL patients(r=0.991). The level of miR-429 not correlate with the age, sex, Hb level, Plt level and immunophenotype of ALL patients (P>0.05). The level of miR-429 was not significantly different between CR patients and control group (P>0.05); the level of miR-429 in PR patients was higher than that in control group and CR patients (P<0.05). The level of miR-429 in NR patients was higher than that in other groups (P<0.05). Kaplan-Meier survival analysis showed that the overall survival rate of ALL patients with low expression of miR-429 was better than that of ALL patients with high expression of miR-429 (P<0.05). Univariate Cox regression analysis showed that leukocyte level, ratio of bone marrow primordial cells, Hb and LDH level, risk grading and miR-429 were the factors influencing overall survival rate in ALL patients (P<0.05). Multivariate Cox regression analysis showed that leukocyte level, ratio of bone marrow primordial cells, risk grading, and miR-429 were the factors influencing overall survival rate (P<0.05).
CONCLUSION: The expression of miR-429 is high in ALL patients, which closely relates to the curative effect and pro-gnosis of ALL patients, and can be used as a reference index for evaluation of clinical prognosis of ALL patients.

PMID: 32027263 [PubMed - indexed for MEDLINE]

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[Effect of MiRNA-145 on Apoptosis of Leukemia HuT 78 Cells and Its Mechanism].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):104-109

Authors: Li ZH, Zhang YP, Xing PT, Zhan XR

Abstract
OBJECTIVE: To investigate the effect and mechanism of miRNA-145 on leukemic cell apoptosis.
METHODS: After transfection of miRNA-145 mimic and negative control mimic in leukemia cells by Lipofectamine 2000 liposome, the MTT assay was used to detect the effect of miRNA-145 on cell proliferation. Flow cytometry was used to detect the effect of miRNA-145 on cell cycle and apoptosis. Western blotting assay was used to detect the expression levels of BCL-2, CDK6, Cyclin D1, BAX, PI3K p-PI3K, p-AKT and AKT.
RESULTS: The relative level of microRNA in HuT 78 cells transfected with miRNA-145 was 2.3±02, which was significantly higher than that in blank control group and miRNA-NC group (P<0.05). MTT assay showed that the proliferation level of HuT 78 cells transfected with miRNA-145 mimic was significantly lower than that of blank control and miRNA-NC group (P<0.05). Flow cytometry showed that the cells at G0/G1, S and G2/M phase of HuT 78 cells were significantly decreased after transfection with miRNA-145 mimic (P<0.05). Annexin V/PI double staining assay showed that the apoptosis rate of HuT 78 cells was 17.6%±3.4%,which was significantly higher than that in blank control group and miRNA-NC group (P<0.05). Western blot showed that the expression levels of BCL-2, CDK6 and Cyclin D1 in HuT 78 cells were significantly lower than those in blank control and miRNA-NC group (P<0.05), and BAX expression in HuT 78 cells was significantly higher than that in blank control and miRNA-NC group (P<0.05). Western blot showed that expression of PI3K, p-PI3K, AKT and p-AKT in HuT 78 cells transfected with miRNA-145 mimic were significantly lower than that in blank control and miRNA-NC group (P<0.05).
CONCLUSION: Upregulation of miRNA-145 may inhibit the proliferation of leukemia cells and promote the apoptosis, which may be related with the inhibition of PI3K/AKT signaling pathway.

PMID: 32027261 [PubMed - indexed for MEDLINE]

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[Correlation of Early Minimal Residual Disease Level with Prognosis in AML Patients with NPM1 Mutation Positive after Chemotherapy].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):93-97

Authors: Wang LJ, Li TT, Sun L, Wu XF, Song Q

Abstract
OBJECTIVE: To analyze the correlation of the minimal residual disease level with the prognosis of the AML patients with NPM1 gene mutation positive after chemotherapy.
METHODS: The clinical data of 112 newly diagnosed adult AML patients with positive NPM1 gene were collected and retrospectively analyzed. The correlation of the transcripts of NPM1 gene mutation with prognosis of patients was analyzed.
RESULTS: In 112 AML patients, the median transcript level of NPM1 gene mutation accounted for 83.68% (5.86%-486.57%), FLT3-ITD mutation positive was found in 44 cases (39.29%), chromosomal abnormalities in 22 cases (19.64%) and complete remission in 96 cases (85.71%). Multivariate logistic regression analysis showed that the initial induction therapy and white blood cell count closely related with complete remission (P<0.05). The median follow-up time was 22 (3-36) months, and the 3-year overall survival rate was 66.07% in 112 patients. Multivariate logistic regression analysis showed that both the high level of minimal residual disease at the initial complete remission and the high level of minimal residual disease after consolidation therapy were the independent risk factors for overall survival (P<0.05).
CONCLUSION: In newly diagnosed adult AML patients with NPM1 mutation positive, the early high level of minimal residual disease after chemotherapy closely relates with poor prognosis.

PMID: 32027259 [PubMed - indexed for MEDLINE]

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[Dihydroartemisinin Induces AML cell Apoptosis by Inhibition of PTEN/AKT pathway].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):88-92

Authors: An YH, DU J, Hou ZW, Sun WD, Zhou Y, Yu XX, Wang X, Wang Y, Tong XM

Abstract
OBJECTIVE: To study the effects of dihydroartemisinin (DHA) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.
METHODS: The effects of DHA on the proliferation of acute myeloid leukemia cells and the inhibitory effect of Z-VAD-FMK on the DHA-induced cell apoptosis were detected by CCK-8 assay. The expression level of cleaved-caspased 3 was detected by indirect immunofluorescence. Western blot was used to quantify the protein expression of PTEN, p-Akt, AKT, β-actin, and the apoptosis-associated proteins, such as C-PARP, Cleaved-caspase3 and Caspase3 respectively.
RESULTS: DHA induced the AML cell apoptosis with concentration-dependent manner (rKasumi-1=-0.959, rKG-1=-0.956). The DHA could induce the accumulation of cleaved-caspase 3 and C-PARP in AML cells, activate PTEN gene and inhibited Akt phosphorylation. Apoptosis inhibitor Z-VAD-FMK could partially restored the activity of DHA-inhibited cell proliferation.
CONCLUSION: Dihydroartemisinin induces AML cell apoptosis by inhibition of PTEN/AKT pathway. Dihydroartemisinin is expected to be a safe and effective drug for treatment of acute myeloid leukemia.

PMID: 32027258 [PubMed - indexed for MEDLINE]

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[Analysis of Clinical Features and Prognosis of Patients with Chronic Neutrophil Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):82-87

Authors: Guo YJ, Wang Y, Wang LH, Zuo YB, Niu ZY, Lin FR, Zhang JY

Abstract
OBJECTIVE: To provide clinical basis for the diagnosis and treatment of chronic neutrophilic leukemia (CNL) and to provide possible molecular targets for the treatment.
METHODS: By summarizing the clinical data of 14 patients with CNL, the clinical characteristics, gene mutation types and possible prognostic factors were analyzed.
RESULTS: Among the 14 patients with CNL, males (9 cases) were more than females (5 cases), with a median age of 57 years old. The detection rate of CSF3R mutation was 92.86% (13/14), including 12 cases (85.71%) with T318I mutation and 1 case of Y799X mutation, and only 1 case was not detected for mutation of CSF3R. The ASXL1 mutation was detected in 42.86% (6/14) of the patients, all of which were nonsense mutations, including 4 cases with R693X and 2 cases with E705X, and 14.29% (2/14) of the patients was detected for SETBP1 mutation, all of which were with D868N mutation. No patients with simultaneous ASXL1 and SETBP1 mutations were found, and JAK2 and CALR mutations were not detected. All of the patients had normal karyotypes. These patients' median survival time was 30 months (95%CI 13.19-46.80), and the influence of age over 60 years old was statistically significant (21.83 months vs 35.35 months) (P<0.05).
CONCLUSION: It is difficult to diagnose CNL. CSF3R T618I mutation is its specific mutation, and ASXL1 mutation and SETBP1 mutation have auxiliary diagnostic significance for CNL. The age>60 years old at diagnosis is a factor of unfavourable prognosis.

PMID: 32027257 [PubMed - indexed for MEDLINE]

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[NRAS Gene Expression and Its Clinical Significance in Patients with Acute Myeloid Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):76-81

Authors: Li TT, Li J, Geng YH, Zhang F, Liu L, Yang YL

Abstract
OBJECTIVE: To investigate the mutation rate and distribution of Homo sapiens neuroblastoma RAS viral oncogene homolog (NRAS) gene in the patients with acute myeloid leukemia.
METHODS: The genomic DNA of bone marrow was screened by polymerase chain reaction (PCR) and sequencing for NRAS mutations. At the same time, the mutations of ASXL1, DNMT3A, TET2, CEBPA, FLT3, IDH2, NPM1 and c-KIT genes were also detected to analyze the relation with NRAS mutations.
RESULTS: A total of 11 NRAS mutations were found in 108 patients with initial acute myeloid leukemia and the mutation rate was 10.2%, including 6 cases of G12D, 3 cases of G13D, and 2 cases of G61K. In the mutation group, the peripheral blood leukocyte count was higher (P<0.05), more likely to occur in the M4 subtype, and the M2 subtype was mutually exclusive (P<0.05). Moreover, the mutant group was more likely to express CD13 than the non-mutation group (P<0.05), while no statistic difference was found in age, gender, hemoglobin level, platelet count, lactate dehydrogenase level, bone marrow blast, cytogenetics, complete remission rate and overall survival (P>0.05).
CONCLUSIONS: The mutation of NRAS gene has no effect on the prognosis of AML patients.

PMID: 32027256 [PubMed - indexed for MEDLINE]

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[Analysis of Clinical Characteristics and Therapeutic Efficacy of Patients with Adult Acute Lymphoblastic Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):68-75

Authors: Xu TT, Wang WM, Fu GM, Wang JM, Jiang ZX

Abstract
OBJECTIVE: To explore the clinical characteristics and therapeutic efficacy of patient with adult acute lymphoblastic leukemia(ALL).
METHODS: Seventy-seven ALL patients diagnosed in the first affiliated hospital of Zhengzhou University from 2018 to 2019 were selected. The immunotyping, fusion gene and gene mutation were detected by flow cytometry, real-time quantitative polymerase chain reaction (RT-PCR) and next generation sequencing (NGS).
RESULTS: Among 77 patients with ALL, 66 were B-ALL, 9 were T-ALL. CD7 and cCD3 were the most valuable for the diagnosis of T-ALL, CD19 and cCD79a were the most valuable for the diagnosis of B-ALL, and CD58, CD123 were highly expressed in B-ALL. Three fusion genes: BCR-ABL (20.8%), MLL-AF4 (5.19%) and E2A-PBX1 (2.60%) were detected by RT-PCR and 10 mutant genes were detected by NGS (the total detection rate was 33.47%). The highest mutation rates were IL-7R (6 cases), NOTCH1 (6 cases), TP53 (5 cases) and FLT-3 (4 cases). Patients with IL-7R, NOTCH1 and TP53 mutations showed poor response to induction chemotherapy.
CONCLUSION: The CD123, IL-7R, NOTCH1 and TP53 may be risk factors for prognosis, however, the increase of case number and prolonging of follow-up time are needed to further confirm.

PMID: 32027255 [PubMed - indexed for MEDLINE]

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[Effect of CD56 Expression on Prognosis of AML Patients with AML/ETO Mutation].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):63-67

Authors: Zhao J, Zhang HT

Abstract
OBJECTIVE: To investigate the expression and prognostic significance of CD56 in the patients suffered from acute myeloid leukemia with AML/ETO mutation.
METHODS: The clinical data of 60 newly diagnosed AML patients with AML/ETO from January 2012 to December 2016 were analyzed retrospectively. The clinical characteristics and outcome between CD56+ and CD56- patients were compared.
RESULTS: There were significant differences in CR rate after one course chemotherapy, relapse rate within 1 year and gene mutations between the CD56 positive and negative patients (P<0.05). The RFS and OS of CD56 positive patients were significantly lower than those of CD56 negative patients (P<0.05).
CONCLUSION: The expression of CD56 may be an important factor of poor prognosis in AML patients with AML/ETO.

PMID: 32027254 [PubMed - indexed for MEDLINE]

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[Expression and Significance of BTLA and Its Ligand HVEM in Patients with Chronic Myelomonocytic Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):56-62

Authors: Li C, Geng SX, Li MM, Su F, Chen XM, Deng CX, Huang X, Lai PL, Weng JY, DU X

Abstract
OBJECTIVE: To investigate the expression and significance of B and T lymphocyte weakening factor (BTLA) in patients with chronic myelomonocytic leukemia (CMML).
METHODS: Real-time PCR was used to detect the expression of BTLA and its ligand HVEM mRNA in 11 patients with chronic myelomonocytic leukemia and 11 normal donors. Flow cytometry was used to detect expression of BTLA and its HVEM on the cell surface of peripheral blood T lymphocytes and γδ T cells.
RESULTS: The median values of BTLA and its ligand HVEM mRNA expression in peripheral blood of patients with CMML were 0.009% and 559.4%, respectively, which were significantly lower than those of normal controls (0.053% and 1031%)(P<0.001). The expression level of BTLA and HVEM on cell surface of peripheral lymphocytes was not significantly different from that in normal controls (P=0.3031 and 0.2576), however, the proportion of peripheral blood T lymphocytes in patients with CMML (median: 37.73%) was significantly lower than that in controls (median 69.23%)(P=0.0005). The expression of BTLA on the surface of γδ T cells in peripheral blood of patients with CMML (median: 23.26%) was significantly lower than that of the controls (median: 52.64%) (P<0.05), and there was no significant abnormality in HVEM expression (P=0.2791).
CONCLUSION: The expression of BTLA and its ligand HVEM, the proportion of T lymphocytes and the expression of BTLA on the surface of γδ T cells in patients with CMML are reduced. The effects of these abnormalities on T cell function and prognosis and efficacy of patients need to be further observed.

PMID: 32027253 [PubMed - indexed for MEDLINE]

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[Relationship between Polymorphism in ALOX5, ALOX5AP and Susceptibility to Myeloid Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):40-50

Authors: Mei F, Wang YF, Yang D, Zuo RX, Shen T, Yang TH, Sa YL

Abstract
OBJECTIVE: To investigate the correlation of single nucleotide polymorphisms (SNP) in arachidonate 5-lipoxygenase gene (ALOX5) rs2029253, rs2228064 and rs2228065 sites, 5-lipoxygenase activating protein gene (ALOX5AP) rs10507391, rs4769874 sites with the risk for genesis of adult myeloid leukemia.
METHODS: By the approval from the hospital ethics committee and the informed consent of participants. 150 patients with myeloid leukemia (ML) as ML group and 134 healthy people as the control group were selected. The genomic DNA was extracted from the samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with directly sequencing, PCR-amplified products were applied to test the polymorphism of 5 sites in ALOX5 and ALOX5AP gene.
RESULTS: A allele frequencies of ALOX5 gene rs2029253 site in the ML group and the control group were 43.0% and 34.3%, respectively. And the G allele frequencies in the ML group and the control group were 57.0% and 65.7%, respectively. The genotype distributions of AA, AG and GG in ALOX5 gene rs2029253 site in the ML group were 32.2%, 21.5% and 46.3% respectively. That in the control group were 15.7%, 37.3% and 47.0% respectively. The genotype AA and A allele frequency of ALOX5 gene rs2029253 site were linked with the increased risk of myeloid leukemia (OR=2.26, 95% CI: 1.43-4.56, P<0.05; OR=1.44, 95% CI: 1.02-2.03, P<0.05). And the genotype AG and allele G reduced the susceptibility to myeloid leukemia (OR=0.46, 95% CI: 0.27-0.78, P<0.01; OR=0.69, 95% CI: 0.50-0.98, P<0.05), however, the polymorphisms of ALOX5 gene rs2228064 and rs2228065 site not correlated with the risk of myeloid leukemia (P>0.05). The A allele frequency of ALOX5AP gene rs10507391 site in the ML group and the control group were 30.7% and 36.2% respectirely. The genotype distribution rates of AA, AT and TT in ALOX5AP gene rs10507391 site in the ML group was 1.3%, 58.7% and 40.0% respectively, that in the control group were 9.7%, 53.0% and 37.3% respectively. The genotype AA of ALOX5AP gene rs10507391 site correlated with the decreased risk of myeloid leukemia (OR=0.13, 95% CI: 0.03-0.57, P<0.05), but the polymorphism of ALOX5AP gene rs4769874 site not correlated with the risk of myeloid leukemia (P>0.05).
CONCLUSION: The genotype AA, AG and allele A, G of ALOX5 rs2029253, as well as ALOX5AP rs10507391 may be correlate with the susceptibility to myeloid leukemia.

PMID: 32027251 [PubMed - indexed for MEDLINE]

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[Expression and Prognostic Value of MiR-155 in Patients with Chronic Lymphocytic Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):34-39

Authors: Wang F, Xu W, Gu WY, Li JY

Abstract
OBJECTIVE: To explore the expression of miR-155 in patients with chronic lymphocytic leukemia (CLL) and its correlation with the clinical and biological features in CLL.
METHODS: The expression of miR-155 was detected by quantitative real time polymerase chain reaction (qRT-PCR) in the peripheral mononuclear cells collected from 73 CLL patients and CD19 positive B cells collected from 60 healthy controls, respectively. The expression of miR-155 in CLL patients was compared with the healthy controls, and the correlation of miR-155 expression with the clinical characteristics of CLL patients such as age, sex, Binet stage, cytogenetic and molecular genetic, as well as the relationship of miR-155 expression level with time to treatment (TTT) and overall survival (OS) was further analysed.
RESULTS: The expression of miR-155 was significantly elevated in CLL patients compared with the healthy controls. Further analysis showed that miR-155 expression decreased in the patients with the mutated immunoglobulin heavy chian variable region (IGHV) as compared with the patients unmutated (P<0.05), and its expression was significant higher in the IGHV-39 family (P<0.05). Fluorescence in situ hybridization (FISH) showed that the expression of miR-155 increased in patients with P53 mmutation/deletion and ATM deletion (P<0.05). However, OS and TTT were not different between the patients with high and low expression of miR-155.
CONCLUSION: MiR-155 is increasingly expresses in CLL patients and correlates with poor prognosis, suggesting its important role in the genesis and progress of CLL.

PMID: 32027250 [PubMed - indexed for MEDLINE]

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[BAX Deletion Accelerates Progression of BCR-ABL-Induced B-ALL in Mice].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):29-33

Authors: Shi L, Long YY, Sha MQ, Luo X, Huang P, Chen Y

Abstract
OBJECTIVE: To explore whether BAX plays a role in the development of Philadelphia chromosome-positive leukemia and related mechanisms.
METHODS: Target-gene knockout mice were used as bone marrow cell donors. Retrovirus over-expressing BCR-ABL were packaged. BCR-ABL-induced B-ALL mouse model was established through donor's B cells transfected by the retrovirus and the B cells over-expressing BCR-ABL were given to the receptor mice by tail vein injection. Western blot was used to detect the protein express and flow cytometry was used to analyze the B cell subpopulations in BAX-/- and WT mouse bone marrows. Kaplan-Meier analysis was used to estimate the survival of diseased mice.
RESULTS: BAX deletion caused faster development of BCR-ABL-induced leukemia in vitro and in vivo. BCR-ABL increased BCL-2 expression and enhanced BCL-2/BAX heterodimer formation.
CONCLUSION: The BAX deletion can accelerate the disease progression of BCR-ABL induced B-ALL.

PMID: 32027249 [PubMed - indexed for MEDLINE]

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[Analysis of Clinical Characteristics of Acute B Lymphoblastic Leukemia with EP300-ZNF384 Fusion Gene Positive].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):24-28

Authors: Yao ZL, Li YF, Li M, Li Y, Li WJ, Li HH, Liu YY, Lin SH, Li FW, Zhang J, Jing Y

Abstract
OBJECTIVE: To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease.
METHODS: The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed.
RESULTS: The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy.
CONCLUSION: The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.

PMID: 32027248 [PubMed - indexed for MEDLINE]

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[Clinical Analysis of Dasatinib and Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):18-23

Authors: Li Y, Wang BJ, Liu W, Liang ZY, Yin Y, Dong YJ, Wang Q, Sun YH, Xu WL, Ren HY

Abstract
OBJECTIVE: To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS: Clinical data of 19 newly diagnosed as Ph+ ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed.
RESULTS: There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively.
CONCLUSION: First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of Ph+ALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.

PMID: 32027247 [PubMed - indexed for MEDLINE]

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[Comparision of Mutational Spectrum between Elderly and Young Adults with Acute Myeloid Leukemia Based on Next Generation Sequencing].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):12-17

Authors: Wang WM, Li YF, Sun L, Jiang ZX, Wan DM, Ma J, Gan SL, Wang F, Cao WJ, Sun H

Abstract
OBJECTIVE: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS).
METHODS: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (<60 years old) were compared.
RESULTS: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively.
CONCLUSION: The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

PMID: 32027246 [PubMed - indexed for MEDLINE]

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[Clinical Characteristics and Prognosis of U2AF1 Mutation in Patients with Acute Myeloid Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):7-11

Authors: Zhao TY, Guan LX, Zheng WS, Wang ML, Cheng LC, Hu YL, Xu YY, Gu ZY, Dou LP

Abstract
OBJECTIVE: To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis.
METHODS: A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed.
RESULTS: The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01).
CONCLUSION: The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.

PMID: 32027245 [PubMed - indexed for MEDLINE]

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[Efficacy of Arsenic Trioxide Combined with ATRA and Chemotherapy for Relapsed Acute Promyelocytic Leukemia Patients].

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):1-6

Authors: Li Y, Liu KQ, Gong BF, Wang Y, Wei H, Lin D, Liu BC, Zhou CL, Wei SN, Zhang GJ, Liu YT, Gong XY, Wang JX, Mi YC

Abstract
OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients.
METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed.
RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications.
CONCLUSION: For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

PMID: 32027244 [PubMed - indexed for MEDLINE]

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Authors: Rendeiro AF, Krausgruber T, Fortelny N, Zhao F, Penz T, Farlik M, Schuster LC, Nemc A, Tasnády S, Réti M, Mátrai Z, Alpár D, Bödör C, Schmidl C, Bock C

Abstract
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease. To define the underlining regulatory dynamics, we analyze high-resolution time courses of ibrutinib treatment in patients with CLL, combining immune-phenotyping, single-cell transcriptome profiling, and chromatin mapping. We identify a consistent regulatory program starting with a sharp decrease of NF-κB binding in CLL cells, which is followed by reduced activity of lineage-defining transcription factors, erosion of CLL cell identity, and acquisition of a quiescence-like gene signature. We observe patient-to-patient variation in the speed of execution of this program, which we exploit to predict patient-specific dynamics in the response to ibrutinib based on the pre-treatment patient samples. In aggregate, our study describes time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring.

PMID: 31996669 [PubMed - indexed for MEDLINE]

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Current Risk Estimate of Breast Implant-Associated Anaplastic Large Cell Lymphoma in Textured Breast Implants.

Plast Reconstr Surg. 2020 02;145(2):446e

Authors: Sheena Y, Smith S, Dua S, Morgan M, Ramakrishnan V

PMID: 31985673 [PubMed - indexed for MEDLINE]

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Breast implant-associated anaplastic large cell lymphoma: A comprehensive review.

Cancer Treat Rev. 2020 Mar;84:101963

Authors: Marra A, Viale G, Pileri SA, Pravettoni G, Viale G, De Lorenzi F, Nolè F, Veronesi P, Curigliano G

Abstract
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized non-Hodgkin lymphoma of T-cell origin. Despite the low incidence of this new disease, the increasing use of breast implants for cosmetic or post-mastectomy reconstruction purposes places BIA-ALC as an emerging and compelling medical challenge. The real BIA-ALCL pathogenesis has not been fully uncovered so far, while different putative causal factors have been proposed. Breast implants with textured surfaces seem to be associated with nearly all cases of BIA-ALCL, while the real the risk of disease development has not been well estimated so far. Late onset, persistent seroma around breast implant represents the classical clinical presentation. Most of the BIA-ALCL patients presents with localized disease, which confers an excellent prognosis. Unlike other non-Hodgkin lymphomas, surgical excision of the mass has a key role in the treatment. For patients with advanced and disseminated diseases, the treatment did not differ from other types of T-cell lymphoma. For these reasons, BIA-ALCL represents an emerging disease which requires multidisciplinary team approach to well define diagnostic workup and treatment for each patient. This review article aims to summarize available data on BIA-ALCL. First, we will outline available data on BIA-ALCL epidemiology, pathogenesis, diagnostic work-up, and treatment. Second, we will point out the potential psychological implications as well as the risk of perception distortion for women with breast implants, especially for those with previous breast cancer. Lastly, we will summarize the current national recommendations regarding textured breast implants and discuss the diagnostic-therapeutic algorithm for BIA-ALCL management.

PMID: 31958739 [PubMed - indexed for MEDLINE]

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[Myelodysplastic syndromes].

Internist (Berl). 2020 Feb;61(2):175-184

Authors: Giagounidis A

Abstract
Myelodysplastic syndromes (MDS)-previously called "preleukemias"-are clonal diseases of the pluripotent hematopoietic stem cell. Their hallmark is peripheral cytopenias. Early forms are characterized by dysplasia of mature cells in the peripheral blood or erythropoiesis, granulopoiesis or megakaryocytes in the bone marrow, and later stages tend to accumulate blasts. About 30% transform into acute myeloid leukemia. MDS are diseases of the elderly and are prognostically divided into lower and higher risk diseases. Median survival times vary accordingly between 6 months and 10 years. Chromosomal abnormalities are identified in 50% of patients, and single or multiple gene mutations occur in 80%. They are the driving force leading to abnormalities in differentiation and to the accumulation of blasts in the bone marrow. Therapeutic options include supportive care, erythropoiesis-stimulating agents, demethylating agents, and allogeneic stem cell transplantation.

PMID: 31925478 [PubMed - indexed for MEDLINE]

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Preparation and Characterization of Fe3O4@MTX Magnetic Nanoparticles for Thermochemotherapy of Primary Central Nervous System Lymphoma in vitro and in vivo.

Int J Nanomedicine. 2019;14:9647-9663

Authors: Dai X, Yao J, Zhong Y, Li Y, Lu Q, Zhang Y, Tian X, Guo Z, Bai T

Abstract
Background: Primary central nervous system lymphomas (PCNSL) are extranodal malignant non-Hodgkin lymphomas (NHL) that arise exclusively in central nervous system (CNS). Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype.
Purpose: To evaluate whether nano drug-loading system-mediated magnetic-targeted thermochemotherapy could produce a better therapeutic effect than single chemotherapy while reducing the use of chemotherapeutic drugs.
Methods: Six groups (control, Fe3O4, MTX, Fe3O4@MTX, Fe3O4 with hyperthermia and Fe3O4@MTX with hyperthermia) were set. Tumor cell apoptosis in each treatment group was detected by flow cytometry. Apoptosis-related gene expressions Caspase-3, Bax and Bcl-2 were detected by qPCR and Western blot; intracranial tumor model of PCNSL was established by intracranial injection of OCI-LY18 tumor cells into BALB/c-Nude mice. Magnetic resonance imaging (MRI) was used to monitor tumor progression and H&E staining was used to observe pathological changes of the tumor tissue.
Results: In vitro, compared with chemotherapy alone, apoptosis rate of Fe3O4@MTX mediated thermochemotherapy group was significantly increased, and expression of apoptosis-inducing gene Caspase-3 and Bax were significantly upregulated in OCI-LY18 cells, while expression of apoptosis-inhibiting Bcl-2 gene was significantly downregulated. In vivo, MRI showed successful generation of intracranial tumor, and tumor volume was significantly smaller in combined thermochemotherapy group than in single chemotherapy group. H&E staining result of tumor tissues in each group was consistent with MRI; tumor cells were significantly reduced in thermochemotherapy group. Expression of apoptosis-related gene Caspase-3 and Bax were significantly upregulated in tumor tissues, while expression of Bcl-2 gene was significantly downregulated.
Conclusion: These results demonstrated in vivo and in vitro that the combined thermochemotherapy of Fe3O4@MTX MNPs was superior to the single MTX chemotherapy with less dosage, which may promote apoptosis of DLBCL cells through the mitochondrial apoptotic pathway and provided a new way for the treatment of PCNSL.

PMID: 31824157 [PubMed - indexed for MEDLINE]

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Diagnosis of West Nile virus encephalitis in a returned traveller.

Med J Aust. 2019 12;211(11):501-502.e1

Authors: Whyler NC, Teng JC, Brewster DJ, Chin R, Cox I, Druce J, Prince HM, Sheffield DA, Teh E, Sarode V

PMID: 31736076 [PubMed - indexed for MEDLINE]

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AMPK activation induced by promethazine increases NOXA expression and Beclin-1 phosphorylation and drives autophagy-associated apoptosis in chronic myeloid leukemia.

Chem Biol Interact. 2020 Jan 05;315:108888

Authors: Medeiros HCD, Colturato-Kido C, Ferraz LS, Costa CA, Moraes VWR, Paredes-Gamero EJ, Tersariol ILS, Rodrigues T

Abstract
Relapse and drug resistance is still major challenges in the treatment of leukemia. Promethazine, an antihistaminic phenothiazine derivative, has been used to prevent chemotherapy-induced emesis, although there is no report about its antitumor potential. Thus, we evaluated the promethazine cytotoxicity against several leukemia cells and the underlying mechanisms were investigated. Promethazine exhibited potent and selective cytotoxicity against all leukemia cell types in vitro at clinically relevant concentrations. Philadelphia positive chronic myeloid leukemia (CML) K562 cells were the most sensitive cell line. The cytotoxicity of promethazine in these cells was triggered by the activation of AMPK and inhibition of PI3K/AKT/mTOR pathway. The subsequent downstream effects were NOXA increase, MCL-1 decrease, and Beclin-1 activation, resulting in autophagy-associated apoptosis. These data highlight targeting autophagy may represent an interesting strategy in CML therapy, and also the antitumor potential of promethazine by acting in AMPK and PI3K/AKT/mTOR signaling pathways. Since this drug is currently used with relative low side effects, its repurposing may represent a new therapeutic opportunity for leukemia treatment.

PMID: 31682805 [PubMed - indexed for MEDLINE]

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Reducing risk in thiopurine therapy.

Xenobiotica. 2020 Jan;50(1):101-109

Authors: Marinaki AM, Arenas-Hernandez M

Abstract
The thiopurine drugs azathioprine and mercaptopurine are effective in the treatment of disorders of immune regulation and acute lymphoblastic leukaemia. Although developed in the 1950s, thiopurines remained relevant in the anti-tumour necrosis factor biologic era, finding widespread use as a co-immunomodulator. Step changes in the management of patients treated with thiopurines have reduced the incidence of severe, sometimes life-threatening toxicity. Testing for thiopurine methyltransferase (TPMT) deficiency directs a safe initial dose for therapy. The introduction of red cell thioguanine nucleotide (TGN) monitoring provides a basis for dose adjustment and the identification of patients with high levels of red cell methylmercaptopurine (MMP) and an increase in the MMP:TGN ratio. These patients are at risk for hepatotoxicity and where TGN levels are sub-therapeutic, non-response to therapy. Switching thiopurine hypermethylators to low-dose thiopurine and allopurinol combination therapy resolves hepatoxicity and increases sub-therapeutic TGN levels to regain clinical response. NUDT15 variants are a common cause of severe myelotoxicity in Asian populations where the frequency of TPMT deficiency is low. There is increasing evidence that testing for NUDT15 and TPMT deficiency in all populations prior to the start of thiopurine therapy is clinically useful and should be the first step in personalising thiopurine therapy.

PMID: 31682552 [PubMed - indexed for MEDLINE]

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Eglerisine, a Novel Sesquiterpenoid Tropolone from Dulacia egleri with Antiproliferative Effect against an Acute Myeloid Leukemia Lineage.

Planta Med. 2020 Jan;86(1):55-60

Authors: R de Novais LM, Ferreira LF, de Sousa PT, Ribeiro TAN, Jacinto MJ, Dos Santos CHC, de Carvalho MG, Torquato HFV, Paredes-Gamero EJ, Silva VCP

Abstract
Chemical investigation of the stems of Dulacia egleri resulted in the isolation of eglerisine (1: ), a compound with a rare sesquiterpenoid tropolone skeleton. Its structure was determined by analysis of spectrometric and spectroscopic data, including HRESIMS, 1D, and 2D NMR. The antiproliferative effects of eglerisine were tested in human leukemia lineages. In the Kasumi-1 lineage, an acute myeloid leukemia cell line, eglerisine reduced cell metabolism, as determined by the resazurin assay. Eglerisine did not induce cell death by either apoptotic or necrotic mechanisms. However, a reduction of the absolute number of cells was observed. Eglerisine induced cell cycle arrest after 72 h of treatment by phosphorylation of H2AX histone, reducing the S phase and increasing the G2 phase of the cell cycle.

PMID: 31622995 [PubMed - indexed for MEDLINE]

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Plasmablastic lymphoma presenting as a brachial artery aneurysm associated with haemodialysis arteriovenous access ligation in a renal transplant patient.

J Vasc Access. 2020 Jan;21(1):120-124

Authors: Franchin M, Amaglio C, Cervarolo MC, Piffaretti G, Uccella S, Iovino D, Ietto G, Carcano G, Tozzi M

Abstract
INTRODUCTION: Plasmablastic lymphoma is a rare and aggressive neoplasm, generally associated with immunodeficiencies and related to latent Epstein-Barr virus infection. This case is the first reported case of plasmablastic lymphoma relapse in aneurysmatic brachial artery wall.
CASE DESCRIPTION: We describe the case of male patient who underwent cadaveric donor kidney transplant when he was 61 years old and radio-cephalic distal arteriovenous fistula ligation 8 months later. After 8 years, he developed gingival plasmablastic lymphoma treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone regimen with subsequent remission. During follow-up, a mid-forearm vascular access was created because of the worsening of renal function. Twenty-two months later, the patient showed a symptomatic 20 mm brachial artery aneurysm with radiological signs of imminent rupture, for which he was surgically treated. The histological evaluation of the brachial artery specimen revealed a relapse of plasmablastic lymphoma in the arterial wall and in an adjacent lymph node.
CONCLUSION: Brachial artery aneurysms are a rare complication in kidney transplant recipients after ligation of arteriovenous access for haemodialysis. Here, we report a case in which this condition is associated with an even rarer plasmablastic lymphoma. A common aetiology, due to immunosuppressive therapy, is postulated for the two coexisting diseases.

PMID: 31244374 [PubMed - indexed for MEDLINE]

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Treatment-associated outcomes of patients with primary ocular adnexal MALT lymphoma after accurate diagnosis.

Int J Clin Oncol. 2019 Dec;24(12):1620-1628

Authors: Masuda Y, Takeuchi K, Kodama T, Fujisaki T, Imaizumi Y, Otsuka E, Ozaki S, Hasebe S, Yakushijin Y

Abstract
BACKGROUND: Differentiation between primary ocular adnexal mucosa-associated lymphoid tissue (POA-MALT) lymphoma and reactive lymphoid hyperplasias sometimes may be difficult. We have examined the treatment-associated mortality of POA-MALT lymphoma after confirmed diagnosis and evaluated their proper treatments.
PATIENTS AND METHODS: From 1991 through 2016, cases of POA-MALT lymphoma were retrospectively analyzed based on their pathological and molecular/immunological diagnoses.
RESULTS: A total of 78 cases with POA-MALT lymphoma with a median age of 66 years were analyzed over median/mean observations of 6.4/7.1 years. Forty-four patients (56%) were diagnosed with IgH gene clonality and 10 patients (13%) were diagnosed with flow cytometric analysis in addition to the pathological decision. The rest (24 patients, 31%) were diagnosed employing pathological decisions of hemato-pathologists and clinical decisions. All patients, except cases of watchful waiting, achieved complete remission. After initial treatment, 68 patients (87%) presented disease-free during the observation period. As treatment, a radiotherapy-based strategy was followed with 15 patients (19%, group A). Immuno-chemotherapy was administered to 24 patients (31%, B). Surgical extraction only was selected for 36 patients (46%, C). Watchful waiting was selected with three patients (4%). Recurrence after the initial treatment was found in one patient (7%) out of A, in three patients (13%) out of B, and in six patients (17%) out of C, respectively. Progression-free survivals at 5 and 10 years were 100 and 100% in A, 95 and 75% in B, and 88 and 81% in C, respectively. The recurrence rates between the patients who were diagnosed with only pathological decision (n = 24) and the patients who were diagnosed with molecular and immunological procedures (n = 54) did not show any statistical differences.
CONCLUSION: Our results indicate that radiotherapy-based treatment strategies for patients with POA-MALT lymphoma show a low rate of recurrence and may improve their prognosis even after the accurate diagnosis. However, contamination of the cases with reactive (polyclonal) lymphoid hyperplasia into those with MALT lymphoma should be carefully removed to avoid unnecessary treatment for malignancies that do not exist.

PMID: 31172332 [PubMed - indexed for MEDLINE]

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