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Significance of WT1 gene detection in the prognosis of acute myeloid leukemia patients with normal karyotype after hematopoietic stem cell transplantation

Yanjun SUN ; Yang XU ; Jiannong CEN ; Huiying QIU ; Suning CHEN ; Aining SUN ; Depei WU

Journal of Leukemia & Lymphoma.2019;28(4):198-204. doi:10.3760/cma.j.issn.1009_9921.2019.04.002

Objective To investigate the monitoring significance of WT1 gene level in the prognosis of acute myeloid leukemia (AML) patients with normal karyotype after hematopoietic stem cell transplantation (HSCT). Methods The clinical data of 115 AML patients with normal karyotype who were treated with HSCT from July 2009 to March 2017 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. The dynamic detection of bone marrow WT1 gene was carried out by using reverse transcription_polymerase chain reaction (RT_PCR). According to the relative expression level median of WT1 gene before transplantation, the whole patients were divided into the two groups (

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Clinical features of different isoforms of PML鄄RARα fusion gene in patients with acute promyelocytic leukemia

Ping WENG ; Shuxia ZHANG ; Xiaofang CHEN ; Shujuan XU ; Jiangrui GUO ; Zhipeng HE ; Yong WU

Journal of Leukemia & Lymphoma.2019;28(4):205-209. doi:10.3760/cma.j.issn.1009_9921.2019.04.003

Objective To explore the clinical features and prognosis of different PML_RARα fusion gene isoforms in acute promyelocytic leukemia (APL). Methods The clinical data of 78 patients initially diagnosed with APL in Fujian Medical University Union Hospital from February 2013 to July 2016 were collected. The clinical features and prognosis of different PML_RARα fusion gene isoforms were analyzed. Results There were 32 females (41%) and 46 males (59%) in 78 patients, with a median age of 40 years old (13-68 years old). The most common PML_RARα fusion gene was L type (48.7%, 38/78), followed by S type (46.2%, 36/78) and V type (5.1%, 4/78). The patients with white blood cell count more than 10×109/L (high_risk) occurred mostly in S type (61.1%, 22/36), compared with V type and L type, and there were statistically different (χ 2 ＝ 7.683, P < 0.05). A total of 78 patients included 8 cases (10.2%) of combined CD34 positive, 17 cases (21.8%) of combined FLT3_ITD mutation, 12 cases (15.4%) of combined DNMT3A mutation and 9 cases (11.5%) of additional chromosomal abnormalities. There were no significant differences in CD34 positive, FLT3_ITD, DNMT3A, and the incidence of additional chromosomal abnormalities among the three different isoforms (P＞0.05). The most common occurrence of retinoic acid syndrome (RAS) during treatment was S type (21/36), while rare for L type and V type (χ2＝ 7.633, P< 0.05). There were no statistical differences in the complete remission (CR) rate and disease_free survival rate among the patients with different PML_RARα isoforms (P＞0.05). Conclusions The clinical characteristics of different PML_RARα fusion gene isoforms are different, including most_common L type, more_common V type and S type in high risk groups; complicated RAS is commonly found in S type during the treatment. And different isoforms have no effect on the CR and DFS rate.

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Efficacy and prognosis analysis of chemotherapy regimens including decitabine in treatment of newly elderly patients with acute myeloid leukemia

Huanhuan TIAN ; Yuying LI ; Jingnan SUN ; Long SU ; Hai LIN ; Yehui TAN ; Sujun GAO

Journal of Leukemia & Lymphoma.2019;28(4):210-214. doi:10.3760/cma.j.issn.1009_9921.2019.04.004

Objective To explore the efficacy and prognostic factors of chemotherapy regimens including decitabine in treatment of elderly patients newly diagnosed with acute myeloid leukemia (AML). Methods The clinical data of 47 elderly patients newly diagnosed with AML (except M3) who received chemotherapy regimens including decitabine in the First Hospital of Jilin University from February 2013 to November 2017 were retrospectively analyzed, including 11 patients treated with single decitabine and 36 patients treated with decitabine combined with low_dose chemotherapy group. The treatment outcome and the impact of different factors on the prognosis were also analyzed. Results Of 47 patients, there were 15 males and 32 females, and the median age was 65 years old (60-83 years old). The overall response rate of decitabine plus low_dose chemotherapy group for 1 course was higher than that of single decitabine group [80.6% (26/36) vs. 27.3% (3/11), χ 2 ＝ 8.693, P＝ 0.003], and the former showed less courses to acquire remission than the latter (u＝ 3.133, P＝ 0.002); however, there was no significant difference in the median overall survival (OS) time between the two groups (14 months vs. 12 months, P＝ 0.950). Univariate analysis indicated that the median OS time in the complete remission (CR) group was longer than that in the non_CR group (17 months vs. 5 months, P <0.01). The median OS time of the elderly patients with primary AML was longer than that of the patients with secondary AML (16 months vs. 6 months, P＝ 0.01). Cox multifactor analysis showed that failing to achieve CR was identified as an independent adverse influencing factor ( HR＝0.180, 95% CI 0.085-0.382, P< 0.01). The incidence of neutropenia with fever in the patients treated with decitabine plus low_dose chemotherapy group was higher than that in single decitabine group [69.4% (25/36) vs. 36.4% (4/11), χ2＝3.902, P＝0.048]. Conclusion For newly elderly AML patients, chemotherapy regimens including decitabine are safe and effective.

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Acute promyelocytic leukemia with NPM鄄RARα fusion gene positive: report of one case and review of literature

Jiawei WU ; Mengqiao GUO ; Shenglan GONG ; Gusheng TANG ; Min LIU ; Jing DING ; Yuesheng ZHANG ; Jianmin WANG ; Jianmin YANG ; Hui CHENG

Journal of Leukemia & Lymphoma.2019;28(4):215-218. doi:10.3760/cma.j.issn.1009_9921.2019.04.005

Objective To investigate the diagnosis, treatment and prognosis of acute promyelocytic leukemia (APL) with NPM_RARα fusion gene positive. Methods One APL patient with NPM_RARα fusion gene positive who was diagnosed by using morphology, immunology, cytogenetics, molecular biology and multiplex fluorescence in situ hybridization in Changhai Hospital in November 2014 was retrospectively analyzed, and the patient was induced with retinoic acid and treated with DA (daunorubicin + cytarabine) regimen, followed by 4 courses of cytarabine consolidation therapy. Results Abnormal promyelocyte accounted for 0.64 by morphology. And the group of cells expressed myeloperoxidase (MPO), CD13, CD15, CD117, and CD7, CD11c, CD79a, CD123 weakly expressed or not by immunophenotype analysis; karyotype analysis showed 45, XY, t(5;17), 7p-,-16[8]/46, idem,+20[5]/45, idem,-8,+20[2]/46, XY[5]; the fusion gene screening showed that the expression level of NPM_RARα was 416.98% compared with that of APL; molecular complete remission was obtained after the consolidation therapy, but the patient relapsed after 34 months. Finally, the patient died of abnormal coagulation and respiratory failure, with overall survival of 35 months. Conclusion APL with NPM_RARα fusion gene positive is a rare type of acute leukemia, and the main treatment method is retinoic acid combined with myeloid chemotherapy regimen, which has a favorable efficacy but a poor prognosis.

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Mixed鄄phenotypic acute leukemia with SET鄄NUP214 fusion gene positive and extramedullary infiltration: report of one case and review of literature

Xiaoli MA ; Xian ZHANG ; Fang WANG ; Yunchao SU ; Xue CHEN ; Yang ZHANG ; Yu ZHANG ; Mingyu WANG ; Wei ZHANG ; Jing ZHANG ; Daijing NIE ; Jiaqi CHEN ; Mingyue LIU ; Ming LIU ; Hongxing LIU

Journal of Leukemia & Lymphoma.2019;28(4):219-222. doi:10.3760/cma.j.issn.1009_9921.2019.04.006

Objective To investigate the clinical and molecular biological characteristics of mixed_phenotypic acute leukemia (MPAL) with SET_NUP214 fusion gene positive and extramedullary infiltration. Methods The clinical characteristics, diagnosis and treatment of one MPAL patient with SET_NUP214 and extramedullary infiltration who was admitted to Hebei Yanda Ludaopei Hospital in November 2017 were analyzed, and the literature was reviewed. Results The patient was diagnosed as MPAL with extramedullary infiltration. Gene detection found SET exon7_NUP214 exon17 fusion positive accompanied with PHF6, SRSF2 and NRAS mutations. After intensive chemotherapy, the patient achieved complete remission, and then received hematopoietic stem cell transplantation (HSCT), followed by early extramedullary relapse after transplantation, and achieved secondary remission after consolidation chemotherapy. Conclusions MPAL with SET_NUP214 fusion gene positive and extramedullary infiltration has a poor prognosis, and it is easy to relapse. Currently, HSCT is the best available treatment strategy for such patients.

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Decitabine combined with full鄄dose and long鄄term pre鄄excitation regimen for treatment of relapsed/refractory acute myeloid leukemia: a clinical study of 32 cases

Ying LIU ; Ruihua MI ; Lin CHEN ; Qingsong YIN ; Fangfang YUAN ; Yuanyuan XIONG ; Xudong WEI

Journal of Leukemia & Lymphoma.2019;28(4):223-226. doi:10.3760/cma.j.issn.1009_9921.2019.04.007

Objective To observe the clinical efficacy and adverse events of decitabine combined with full_dose and long_term pre_excitation regimen as a induction therapy for relapsed/refractory acute myeloid leukemia (AML). Methods A total of 32 patients with relapsed/refractory AML in Henan Provincial Cancer Hospital from May 2013 to February 2018 were enrolled. All the patients were treated with decitabine combined with full_dose and long_term pre_excitation regimen, including 15 patients who received decitabine combined with CAG regiemtn, and 17 patients who received decitabine combined with CHAG regimen: 25 mg decitabine, intravenous drip, from day 1 to day 3; cytarabine (10-15 mg/m2) administered subcutaneously every 12 h one time, from day 4 to day 17 or more; homoharringtonine (1 mg/m2) intravenous drip, administered intravenously from day 4 to day 10 or more; aclacinomycin (8-10 mg/m2), intravenous drip, administered intravenously from day 4 to day 11 or more; granulocyte colony_stimulating factor (G_CSF) (100-200 μg/m2), subcutaneous injection, and it began 1 day before chemotherapy, adjusted according to the blood cell count; the therapeutic effect and adverse reactions of the patients were observed. Results There were 29 patients (90.6% ) with complete remission (CR), 3 patients (9.4% ) with partial remission (PR), and the overall response (CR+PR) rate was 100.0% (32/32). In decitabine combined with CAG regimen group, 13 patients achieved CR; in decitabine combined with CHAG regimen group, 16 patients achieved CR, and there was no statistically significant difference in the efficacy between the two groups (P＝0.589). The main adverse reactions were agranulocytosis, thrombocytopenia, secondary infection and fever, and no serious adverse events occurred. Conclusion Decitabine combined with full_dose and long_term pre_excitation regimen has a favorable efficacy and safety, which provides a new therapy for relapsed/refractory AML.

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Relationship between WT1 gene mutation and prognosis of acute myeloid leukemia: a Meta鄄analysis

Jing XU ; Zhifang XU ; Jinjun HU ; Hongwei WANG

Journal of Leukemia & Lymphoma.2019;28(4):227-232. doi:10.3760/cma.j.issn.1009_9921.2019.04.008

Objective To summarize the relationship between WT1 gene mutation and prognosis of acute myeloid leukemia (AML). Methods The related literatures were searched in PubMed, Google Scholar and Cochrane Library databases, and the deadline was April 2, 2018. The Meta_analysis was performed by using Review Manager 5.2 software. Results A total of 9 literatures were included. Meta analysis showed that for the pediatric AML patients, the overall survival (OS) time in the WT1 gene mutated group was shorter than that in the wild_type group ( HR＝1.41, 95% CI 1.07-1.87, P＝0.01). For the total AML patients, the relapse_free survival (RFS) time in the WT1 gene mutated group was shorter than that in the wild_type group ( HR＝2.21, 95% CI 1.15-3.93, P＝0.02), but there was no significant difference in OS and disease_free survival (DFS) time between the two groups ( HR＝1.65, 95% CI 0.97-2.80, P＝0.06; HR＝0.46, 95% CI 0.08-2.57, P＝0.38). For the AML patients with normal karyotype and adult AML patients, there was no difference in OS time between the WT1 gene mutated group and wild_type group ( HR＝ 2.66, 95% CI 0.57-12.31, P＝ 0.21;HR＝ 2.10, 95% CI 0.70-6.30, P＝ 0.18). Conclusion WT1 gene mutation is a risk factor affecting OS of pediatric AML patients and RFS of general AML patients.

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Progress of clonal hematopoiesis of indeterminate potential

Yubin DING ; Yufeng TANG ; Xudong TANG

Journal of Leukemia & Lymphoma.2019;28(4):245-247. doi:10.3760/cma.j.issn.1009_9921.2019.04.014

Clonal hematopoiesis is a common aging_associated biological state. The incidence of malignant neoplasms for the patients with clonal hematopoiesis of indeterminate potential (CHIP) is 0.5%-1% every year. Potential factors of clonal progression in hematopoietic cells have been summarized, including disordered endogenous immunity caused by the augmentation of proliferative pressure, chromosomal instability caused by telomeres short; the amplification of clonal stem cells, acquisition of new mutations, and aging_associated changes in hematopoietic stem cells, including altered DNA damage response, an altered transcriptional program and epigenetic alterations while failing to support healthy hematopoiesis. CHIP is a vascular risk factor driven by interactions between clonal monocytes_macrophages and the endothelium, as well as a neoplastic progression risk factor driven by the acquisition of additional somatic mutations in the context of many other influences on hematopoiesis and clonal balance. Strategies to reduce the clonal burden associated with CHIP and to inhibit the key inflammatory pathways leading to atherosclerosis could improve the prognosis of the patients.

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Autophagy and acute leukemia treatment

Xinyue LIANG ; Dengju LI

Journal of Leukemia & Lymphoma.2019;28(4):248-251. doi:10.3760/cma.j.issn.1009_9921.2019.04.015

Autophagy plays an important dual role in the occurrence and development of acute leukemia, inducing the apoptosis of leukemia cells to suppress the development of acute leukemia, and protecting the leukemia cells to sustain the survival and to resist the apoptosis induced by chemotherapy drugs. Some studies have showed that the drug sensitivity of acute leukemia cells can be improved by regulating autophagy to induce the apoptosis of leukemia cells, and thus, regulating autophagy is expected to be an effective therapeutic strategy of refractory/relapsed acute leukemia. This article reviews the recent progress of autophagy and acute leukemia treatment.

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Progress of exosomes in leukemic microenvironment

Yujing YANG ; Xuezhong ZHANG

Journal of Leukemia & Lymphoma.2019;28(4):251-254. doi:10.3760/cma.j.issn.1009_9921.2019.04.016

Exosomes belong to microvesicle structures widely distributed in many body fluids secreted by a variety of living cells, which can carry biological information molecules such as nucleic acids, proteins and lipids derived from parental cells, being the communication carriers among cells. Exosomes play a critical role in cancer progression and participate in tumor cell proliferation, tumor migration, immune escape and angiogenesis. In hematologic system, exosomes involve in the crosstalk between leukemia cells and the surrounding environment, promote the formation of leukemia microenvironment and act as immunomodulators, which will be a potential direction for its therapeutic research. This article reviews the biological characteristics of exosomes and their roles in leukemic tumor microenvironment and immune regulation.

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