Pub Date : 2020-01-25DOI: 10.3760/CMA.J.ISSN.1009-9921.2020.01.007
Wenli Zhang, C. Hou, Meng-jun Shan, Yin Liu, Dong Wang, Qiao Cheng, Yang Xu, Depei Wu
Objective To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML). Methods The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared. Results There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS (HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS (HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse (HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS (HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS (HR = 2.308, 95%CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05). Conclusions The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor. Key words: Leukemia, myeloid, acute; Elderly; Hematopoietic stem cell transplantation; Prognosis
{"title":"Prognostic analysis of allogeneic hematopoietic stem cell transplantation in treatment of elderly patients with acute myeloid leukemia","authors":"Wenli Zhang, C. Hou, Meng-jun Shan, Yin Liu, Dong Wang, Qiao Cheng, Yang Xu, Depei Wu","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.007","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.007","url":null,"abstract":"Objective \u0000To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML). \u0000 \u0000 \u0000Methods \u0000The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared. \u0000 \u0000 \u0000Results \u0000There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS (HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS (HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse (HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS (HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS (HR = 2.308, 95%CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05). \u0000 \u0000 \u0000Conclusions \u0000The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor. \u0000 \u0000 \u0000Key words: \u0000Leukemia, myeloid, acute; Elderly; Hematopoietic stem cell transplantation; Prognosis","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"30-36"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41798539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To investigate the clinical efficacy of second-generation tyrosine kinase inhibitor dasatinib monotherapy in the treatment of relapsed and refractory Philadelphia chromosome positive (Ph+) acute leukemia. Method: Data were collected from 2 patients with relapsed and refractory Ph+acute leukemia treated with dasatinib monotherapy at Luoyang Central Hospital affiliated to Zhengzhou University in February 2015 and February 2016, and their efficacy and prognosis were analyzed. Literature review was also conducted. The results showed that both patients were male, aged 1 and 21 years, respectively. Two patients achieved complete remission (CR) after single drug consolidation therapy with dasatinib. One patient survived for a long time after reaching CR, and one patient relapsed after 5 months of CR. Conclusion: The single drug consolidation therapy with dasatinib has a good relief effect on Ph+acute leukemia and can prolong the survival time of patients. Dashatinib monotherapy can be used as a consolidation therapy for Ph+acute leukemia patients who have not undergone hematopoietic stem cell transplantation.
{"title":"Dasatinib alone for treatment of relapsed/refractory philadelphia chromosome-positive acute leukemia sustained remission: report of two cases and review of literature","authors":"Shuanglin Wang, Shuli Guo, Xiaoyan Xu, Huirui Wang","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.013","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.013","url":null,"abstract":"目的 \u0000探讨二代酪氨酸激酶抑制剂达沙替尼单药治疗复发难治费城染色体阳性（Ph+）急性白血病的临床效果。 \u0000 \u0000 \u0000方法 \u0000收集2015年2月和2016年2月郑州大学附属洛阳中心医院收治的应用达沙替尼单药治疗的2例复发难治Ph+急性白血病患者资料，分析其疗效和预后，并进行文献复习。 \u0000 \u0000 \u0000结果 \u00002例患者均为男性，年龄分别为1、21岁。2例患者经达沙替尼单药巩固治疗后均获得完全缓解（CR），1例达CR后长期生存，1例CR 5个月后复发。 \u0000 \u0000 \u0000结论 \u0000达沙替尼单药巩固治疗Ph+急性白血病有较好的缓解效果，可延长患者生存时间。达沙替尼单药可作为未进行造血干细胞移植的Ph+急性白血病患者的巩固治疗方案。","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"57-60"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45004502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective To investigate the drug resistance of kaempferol reversed adriamycin (ADM)-resistant K562/ADM cells in chronic myelogenous leukemia (CML) and its related mechanism. Methods Methyl thiazolyl tetrazolium (MTT) method was used to detect the toxicity of ADM on K562 and K562/ADM cells for 24 h. The half inhibitory concentration (IC50) of ADM and the drug resistance multiple for 24 h were calculated. MTT method was used to detect the toxicity of kaempferol on K562/ADM cells for 24 h. The 5% inhibitory concentration (IC5) and 10% inhibitory concentration (IC10) of kaempferol for 24 h were calculated to determine the concentration of kaempferol in the subsequent experiments. And the cells untreated by the kaempferol were selected as the control group. The cell inhibition after the treatment of ADM for 24 h of the blank control group and kaempferol intervention group was detected by using MTT method. And then the cell inhibition for 24 h and ADM IC50 for 24 h in the above groups were calculated. The ratio of IC50 in the blank control group and kaempferol group was the reversal drug resistance multiple of kaempferol. The fluorescence intensity of ADM in K562/ADM cells treated by kaempferol was detected by using flow cytometry. Western blotting was used to detect the expressions of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), phosphorylated p38 (p-p38), and total p38 (t-p38) protein in K562/ADM cells after the treatment of kaempferol, the specific inhibitor of p38-MAPK signaling pathway SB202190, and the combination of kaempferol and SB202190. Results After the treatment of ADM for 24 h, the IC50 value of K562 and K562/ADM cells was (0.9±0.6), (28.1 ±3.5) μg/ml, respectively. The drug resistance multiple of K562/ADM cells on the treatment of ADM for 24 h was 31.16 compared with the K562 cells. MTT method showed that kaempferol inhibited the proliferation of K562/ADM cells in a dose-dependent manner. According to the IC5 and IC10, 0.5 μmol/L and 1.0 μmol/L kaempferol were determined to do the subsequent experiments. After the combined interaction of kaempferol and ADM for 24 h, the ADM IC50 of K562/ADM cells in the blank control group, 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was (33.7±5.7), (21.4±0.6), (15.9±1.8) μg/ml, respectively (F = 30.85, P 0.05); SB202190 could reduce the relative expressions of P-gp, MRP1 and p-p38 protein (all P 0.05). Conclusions Kaempferol can decrease the relative expressions of P-gp and MRP1 in K562/ADM cells by inhibiting p38-MAPK pathway, so as to increase the concentrations of ADM and to reverse the drug resistance of K562/ADM cells. Key words: Leukemia, myelogenous, chronic; Drug resistance, neoplasm; Kaempferol; Doxorubicin; P-glycoprotein; Multidrug resistance-associated protein 1; p38; MAP kinase; K562/ADM cells
{"title":"Kaempferol in reversing drug resistance of chronic myelogenous leukemia K562/ADM cells and its related mechanism","authors":"Yingxue Liu, Xiu-hong Jia, Lin Li, Huiying Yin, Cong Zhu, Pei-feng Duan","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.006","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.006","url":null,"abstract":"Objective \u0000To investigate the drug resistance of kaempferol reversed adriamycin (ADM)-resistant K562/ADM cells in chronic myelogenous leukemia (CML) and its related mechanism. \u0000 \u0000 \u0000Methods \u0000Methyl thiazolyl tetrazolium (MTT) method was used to detect the toxicity of ADM on K562 and K562/ADM cells for 24 h. The half inhibitory concentration (IC50) of ADM and the drug resistance multiple for 24 h were calculated. MTT method was used to detect the toxicity of kaempferol on K562/ADM cells for 24 h. The 5% inhibitory concentration (IC5) and 10% inhibitory concentration (IC10) of kaempferol for 24 h were calculated to determine the concentration of kaempferol in the subsequent experiments. And the cells untreated by the kaempferol were selected as the control group. The cell inhibition after the treatment of ADM for 24 h of the blank control group and kaempferol intervention group was detected by using MTT method. And then the cell inhibition for 24 h and ADM IC50 for 24 h in the above groups were calculated. The ratio of IC50 in the blank control group and kaempferol group was the reversal drug resistance multiple of kaempferol. The fluorescence intensity of ADM in K562/ADM cells treated by kaempferol was detected by using flow cytometry. Western blotting was used to detect the expressions of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), phosphorylated p38 (p-p38), and total p38 (t-p38) protein in K562/ADM cells after the treatment of kaempferol, the specific inhibitor of p38-MAPK signaling pathway SB202190, and the combination of kaempferol and SB202190. \u0000 \u0000 \u0000Results \u0000After the treatment of ADM for 24 h, the IC50 value of K562 and K562/ADM cells was (0.9±0.6), (28.1 ±3.5) μg/ml, respectively. The drug resistance multiple of K562/ADM cells on the treatment of ADM for 24 h was 31.16 compared with the K562 cells. MTT method showed that kaempferol inhibited the proliferation of K562/ADM cells in a dose-dependent manner. According to the IC5 and IC10, 0.5 μmol/L and 1.0 μmol/L kaempferol were determined to do the subsequent experiments. After the combined interaction of kaempferol and ADM for 24 h, the ADM IC50 of K562/ADM cells in the blank control group, 0.5 μmol/L kaempferol group and 1.0 μmol/L kaempferol group was (33.7±5.7), (21.4±0.6), (15.9±1.8) μg/ml, respectively (F = 30.85, P 0.05); SB202190 could reduce the relative expressions of P-gp, MRP1 and p-p38 protein (all P 0.05). \u0000 \u0000 \u0000Conclusions \u0000Kaempferol can decrease the relative expressions of P-gp and MRP1 in K562/ADM cells by inhibiting p38-MAPK pathway, so as to increase the concentrations of ADM and to reverse the drug resistance of K562/ADM cells. \u0000 \u0000 \u0000Key words: \u0000Leukemia, myelogenous, chronic; Drug resistance, neoplasm; Kaempferol; Doxorubicin; P-glycoprotein; Multidrug resistance-associated protein 1; p38; MAP kinase; K562/ADM cells","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"23-29"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44058790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-25DOI: 10.3760/CMA.J.ISSN.1009-9921.2020.01.009
X. Hua, Biao Wang, Wei Wu, Z. Shangguan, Liang Tang
Objective To investigate the causes of ineffective platelet transfusion in patients with hematologic malignancies during myelosuppression and the therapeutic effect of rituximab. Methods A total of 180 patients with different hematologic malignancies in the First People's Hospital of Changzhou from January 2017 to December 2018 were selected. And the incidence of ineffective platelet transfusion during myelosuppression was observed. The changes of T and B lymphocyte subgroups and platelet counts before and after rituximab therapy in acute leukemia patients with platelet antibody-positive were compared, and the incidence of ineffective platelet transfusion with different platelet suspensions was analyzed. Results The ineffective platelet transfusion was observed in 45 of 180 patients (25.0%) during myelosuppression, including 30 (27.8%) of 108 patients with acute leukemia, 10 (23.3%) of 43 patients with myelodysplastic syndrome, 2 (13.3%) of 15 patients with malignant lymphoma, and 3 (21.4%) of 14 patients with multiple myeloma. The incidence of ineffective platelet transfusion in patients transfused with irradiated leukocyte depleted apheresis platelets (17.0%, 16/94) was lower than that in those with apheresis platelets (33.7%, 29/86), and the difference was statistically significant (χ2 = 6.68, P = 0.01). In 8 acute leukemia patients with platelet antibody-positive and the ineffective platelet transfusion after rituximab therapy, the increase of platelet count was observed in 5 patients. The differences of levels of CD19, CD20, CD4 and platelet count before and after treatment with rituximab were statistically significant (all P < 0.05). Conclusions The incidence of ineffective platelet transfusion is the highest in acute leukemia patients. Transfusion of human leukocyte antigen-matched platelets can improve the effect of platelet transfusion. Rituximab is effective in the ineffective platelets transfusion caused by immune factors. The incidence of ineffective platelet transfusion in irradiated leukocyte depleted apheresis platelets is lower compared with that in apheresis platelets. Key words: Hematologic neoplasms; Myelosuppression; Platelet transfusion; Medical futility
目的探讨恶性血液病患者骨髓抑制期输血小板无效的原因及利妥昔单抗的治疗效果。方法选取常州市第一人民医院2017年1月至2018年12月收治的180例不同类型恶性血液病患者。观察骨髓抑制期间血小板输注无效的发生率。比较血小板抗体阳性急性白血病患者利妥昔单抗治疗前后T、B淋巴细胞亚群及血小板计数的变化，并分析不同血小板混悬液输注无效血小板的发生率。结果180例骨髓抑制患者中45例(25.0%)出现血小板输注无效，其中急性白血病108例30例(27.8%)，骨髓增生异常综合征43例10例(23.3%)，恶性淋巴瘤15例2例(13.3%)，多发性骨髓瘤14例3例(21.4%)。输注放射性白细胞耗竭单采血小板患者血小板输注无效发生率(17.0%，16/94)低于输注单采血小板患者(33.7%，29/86)，差异有统计学意义(χ2 = 6.68, P = 0.01)。8例急性白血病患者血小板抗体阳性，经利妥昔单抗治疗后输血小板无效，其中5例患者血小板计数升高。利妥昔单抗治疗前后CD19、CD20、CD4、血小板计数差异均有统计学意义(P < 0.05)。结论急性白血病患者血小板输注无效发生率最高。输注人白细胞抗原匹配的血小板可改善血小板输注的效果。利妥昔单抗对免疫因素引起的血小板输注无效有效。照射后白细胞耗竭的单采血小板输注无效的发生率低于单采血小板输注无效的发生率。关键词:血液肿瘤;Myelosuppression;血小板输血;医疗徒劳
{"title":"Study on the ineffective platelet transfusion in patients with hematologic malignancies during myelosuppression","authors":"X. Hua, Biao Wang, Wei Wu, Z. Shangguan, Liang Tang","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.009","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.009","url":null,"abstract":"Objective \u0000To investigate the causes of ineffective platelet transfusion in patients with hematologic malignancies during myelosuppression and the therapeutic effect of rituximab. \u0000 \u0000 \u0000Methods \u0000A total of 180 patients with different hematologic malignancies in the First People's Hospital of Changzhou from January 2017 to December 2018 were selected. And the incidence of ineffective platelet transfusion during myelosuppression was observed. The changes of T and B lymphocyte subgroups and platelet counts before and after rituximab therapy in acute leukemia patients with platelet antibody-positive were compared, and the incidence of ineffective platelet transfusion with different platelet suspensions was analyzed. \u0000 \u0000 \u0000Results \u0000The ineffective platelet transfusion was observed in 45 of 180 patients (25.0%) during myelosuppression, including 30 (27.8%) of 108 patients with acute leukemia, 10 (23.3%) of 43 patients with myelodysplastic syndrome, 2 (13.3%) of 15 patients with malignant lymphoma, and 3 (21.4%) of 14 patients with multiple myeloma. The incidence of ineffective platelet transfusion in patients transfused with irradiated leukocyte depleted apheresis platelets (17.0%, 16/94) was lower than that in those with apheresis platelets (33.7%, 29/86), and the difference was statistically significant (χ2 = 6.68, P = 0.01). In 8 acute leukemia patients with platelet antibody-positive and the ineffective platelet transfusion after rituximab therapy, the increase of platelet count was observed in 5 patients. The differences of levels of CD19, CD20, CD4 and platelet count before and after treatment with rituximab were statistically significant (all P < 0.05). \u0000 \u0000 \u0000Conclusions \u0000The incidence of ineffective platelet transfusion is the highest in acute leukemia patients. Transfusion of human leukocyte antigen-matched platelets can improve the effect of platelet transfusion. Rituximab is effective in the ineffective platelets transfusion caused by immune factors. The incidence of ineffective platelet transfusion in irradiated leukocyte depleted apheresis platelets is lower compared with that in apheresis platelets. \u0000 \u0000 \u0000Key words: \u0000Hematologic neoplasms; Myelosuppression; Platelet transfusion; Medical futility","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"41-44"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43543747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-25DOI: 10.3760/CMA.J.ISSN.1009-9921.2020.01.002
Z. Cao, Jun Ma
Chronic myeloid leukemia (CML) has made a milestone progress due to the development of the first generation tyrosine kinase inhibitor(TKI). Nowadays, most clinical trials in CML focus on discontinuation, even the second discontinuation, and the third generation TKI against T315I mutation. The conventional treatments are more focused on decreasing BCR-ABL transcripts rapidly. At the same time, the treatment management of some special patients has been valued. Key words: Leukemia, myelogenous, chronic, BCR-ABL positive; Drug therapy, combination; Tyrosine kinase inhibitor; Digital polymerase chain reaction; Discontinuation trial
{"title":"Diagnosis and treatment progress of chronic myeloid leukemia","authors":"Z. Cao, Jun Ma","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.002","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.002","url":null,"abstract":"Chronic myeloid leukemia (CML) has made a milestone progress due to the development of the first generation tyrosine kinase inhibitor(TKI). Nowadays, most clinical trials in CML focus on discontinuation, even the second discontinuation, and the third generation TKI against T315I mutation. The conventional treatments are more focused on decreasing BCR-ABL transcripts rapidly. At the same time, the treatment management of some special patients has been valued. \u0000 \u0000Key words: \u0000Leukemia, myelogenous, chronic, BCR-ABL positive; Drug therapy, combination; Tyrosine kinase inhibitor; Digital polymerase chain reaction; Discontinuation trial","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"6-8"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47980183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-25DOI: 10.3760/CMA.J.ISSN.1009-9921.2020.01.004
Hongxing Liu, Xiaosu Zhou, Fang Wang, P. Cao, Jiancheng Fang
The new wave of artificial intelligence pushed by deep learning algorithms has dramatically promoted the development of big data analysis technology. On the other hand, advances in life sciences represented by high-throughput genome sequencing have provided massive medical data. Artificial intelligence technology has also provided a powerful tool for hematological malignancy research. This article introduces related research progress in the 61st American Society of Hematology Annual Meeting. Key words: Hematologic neoplasms; Artificial intelligence; High-throughput nucleotide sequencing; Big data
{"title":"Progress of big data analysis and artificial intelligence technology for hematologic neoplasms","authors":"Hongxing Liu, Xiaosu Zhou, Fang Wang, P. Cao, Jiancheng Fang","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.004","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.004","url":null,"abstract":"The new wave of artificial intelligence pushed by deep learning algorithms has dramatically promoted the development of big data analysis technology. On the other hand, advances in life sciences represented by high-throughput genome sequencing have provided massive medical data. Artificial intelligence technology has also provided a powerful tool for hematological malignancy research. This article introduces related research progress in the 61st American Society of Hematology Annual Meeting. \u0000 \u0000Key words: \u0000Hematologic neoplasms; Artificial intelligence; High-throughput nucleotide sequencing; Big data","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"17-19"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44361364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective To investigate the expressions of tissue factor (TF) and vascular endothelial growth factor (VEGF) in diffuse large B-cell lymphoma (DLBCL) and their clinical significances. Methods The clinical data of 80 cases of DLBCL diagnosed at the Second People's Hospital of Lianyungang from January 2010 to December 2017 were collected, and 30 cases of reactive hyperplasia of lymph node (RLN) were selected as the controls. The expressions of TF and VEGF in the two groups were detected by using immunohistochemical staining. Results The positive rate of TF and VEGF in the DLBCL group was higher than that in the RLN group [TF: 86.3% (69/80) vs. 50.0% (15/30) ; VEGF: 90.0% (72/80) vs. 53.3% (16/30) ; both P 0.05). The positive rate of TF in DLBCL patients with B symptom, increased LDH, physical status grade ≥2, and extranodal lesion number >1 was higher (all P 1 was higher (all P < 0.05). The positive rate of TF in international prognostic index (IPI) high-risk group was higher than that in low-risk group (P < 0.01); the positive rate of VEGF in IPI high-risk group and middle-high-risk group was higher than that in low-risk group (all P < 0.01). The expressions of TF (r = 0.491, P < 0.01) and VEGF (r = 0.529, P < 0.01) were positively correlated with IPI. The overall survival rates of TF and VEGF low-expression group were higher than those of TF and VEGF high-expression group (both P < 0.05). Conclusion The expressions of TF and VEGF are highly expressed in DLBCL, which is associated with the IPI. It can provide a reference value in evaluating prognosis of DLBCL. Key words: Lymphoma, large B-cell, diffuse; Vascular endothelial growth factors; Tissue factor; International prognostic index
{"title":"Expressions of tissue factor and vascular endothelial growth factor in diffuse large B-cell lymphoma and their clinical significances","authors":"Ya-jun Jiang, Gui-hua Zhu, Yao He, Xingxing Chai, Xiaoyun Yang, Fanjing Meng, Wan-chuan Zhuang","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.010","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.010","url":null,"abstract":"Objective \u0000To investigate the expressions of tissue factor (TF) and vascular endothelial growth factor (VEGF) in diffuse large B-cell lymphoma (DLBCL) and their clinical significances. \u0000 \u0000 \u0000Methods \u0000The clinical data of 80 cases of DLBCL diagnosed at the Second People's Hospital of Lianyungang from January 2010 to December 2017 were collected, and 30 cases of reactive hyperplasia of lymph node (RLN) were selected as the controls. The expressions of TF and VEGF in the two groups were detected by using immunohistochemical staining. \u0000 \u0000 \u0000Results \u0000The positive rate of TF and VEGF in the DLBCL group was higher than that in the RLN group [TF: 86.3% (69/80) vs. 50.0% (15/30) ; VEGF: 90.0% (72/80) vs. 53.3% (16/30) ; both P 0.05). The positive rate of TF in DLBCL patients with B symptom, increased LDH, physical status grade ≥2, and extranodal lesion number >1 was higher (all P 1 was higher (all P < 0.05). The positive rate of TF in international prognostic index (IPI) high-risk group was higher than that in low-risk group (P < 0.01); the positive rate of VEGF in IPI high-risk group and middle-high-risk group was higher than that in low-risk group (all P < 0.01). The expressions of TF (r = 0.491, P < 0.01) and VEGF (r = 0.529, P < 0.01) were positively correlated with IPI. The overall survival rates of TF and VEGF low-expression group were higher than those of TF and VEGF high-expression group (both P < 0.05). \u0000 \u0000 \u0000Conclusion \u0000The expressions of TF and VEGF are highly expressed in DLBCL, which is associated with the IPI. It can provide a reference value in evaluating prognosis of DLBCL. \u0000 \u0000 \u0000Key words: \u0000Lymphoma, large B-cell, diffuse; Vascular endothelial growth factors; Tissue factor; International prognostic index","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"45-49"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43322616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-25DOI: 10.3760/CMA.J.ISSN.1009-9921.2020.01.008
Yu Zhang, Yang Zhang, Fang Wang, Mingyu Wang, Hong Liu, P. Cao, Xiaoli Ma, Xue Chen, W. Teng, Xian Zhang, Mangju Wang, Hongxing Liu
Objective To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL). Methods A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams. Results There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. Conclusions ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor. Key words: Leukemia, biphenotypic, acute; Mutation; Tyrosine kinase inhibitor
{"title":"Characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor in patients with mixed phenotype acute leukemia","authors":"Yu Zhang, Yang Zhang, Fang Wang, Mingyu Wang, Hong Liu, P. Cao, Xiaoli Ma, Xue Chen, W. Teng, Xian Zhang, Mangju Wang, Hongxing Liu","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.008","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.008","url":null,"abstract":"Objective \u0000To analyze the incidence and mutation characteristics of FLT3 gene mutation and clinical efficacy of tyrosine kinase inhibitor (TKI) in patients with mixed phenotype acute leukemia (MPAL). \u0000 \u0000 \u0000Methods \u0000A total of 48 patients with MPAL who were admitted to Hebei Yanda Lu Daopei Hospital from June 2015 to February 2018 were retrospectively analyzed. The common mutated 58 genes in hematologic malignancies were detected by using amplicon-targeted next generation sequencing, of which internal tandem duplication (ITD) and point mutation occurred in the hotspot region of exon 14, 15 and 20 in FLT3 gene. Multiplex polymerase chain reaction (PCR) analysis was used to detect 35 gene fusions in hematological neoplams. \u0000 \u0000 \u0000Results \u0000There were 7 cases of FLT3 mutation in 48 MPAL patients, which were all ITD mutations. The median length of the inserts of FLT3-ITD was 48 bp, and one MPAL patient carried 2 multiple length inserts simultaneously, and the median variant allele frequency (VAF) was 40.5% (7.9%-84.7%). There were no statistically significant differences in clinical and genetic characteristics between FLT3 mutation-positive and FLT3 mutation-negative MPAL patients (both P > 0.05). Among 7 FLT3 mutation-positive MPAL patients, 4 cases were often accompanied with RUNX1 mutation. A total of 4 MPAL patients with FLT3-ITD-positive received sorafenib or sunitinib combined chemotherapy, and 3 of them achieved complete remission. \u0000 \u0000 \u0000Conclusions \u0000ITD mutation is the main part in the FLT3 mutation of MPAL patients. FLT3-ITD-positive MPAL patients are often accompanied with RUNX1 mutation, which may benefit from targeted therapy with FLT3 kinase inhibitor. \u0000 \u0000 \u0000Key words: \u0000Leukemia, biphenotypic, acute; Mutation; Tyrosine kinase inhibitor","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"37-40"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48842234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-25DOI: 10.3760/CMA.J.ISSN.1009-9921.2020.01.012
Jing Yang, Jian Wang, Yaqin Mu, Xiying Wang, Lijuan Zhang, Xuping Wang, L. Diao, Wen-sheng Ge, Wenyuan Jiang, Xiaodong Wang
Objective To explore the effect of high mobility group box-1 protein (HMGB1) on the balance of Th17/Treg in patients with immune thrombocytopenia (ITP). Methods A total of 30 patients who were first diagnosed as ITP in the Fifth People's Hospital of Datong from July 2017 to April 2018 were selected as the case group, and another 30 healthy volunteers in the corresponding period were taken as the control group. The proportion of Th17 and Treg cells was detected by using flow cytometry, and the concentration of HMGB1, interleukin (IL)-17 and transforming growth factor β (TGF-β) in plasma was tested by using enzyme-linked immunosorbent assay (ELISA). Isolated peripheral blood mononuclear cells (PBMC) were cultured in vitro. After the treatment with recombinant human HMGB1 (rhHMGB1), real-time polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression changes in Treg cell transcription factor intracellular forkhead helix transcription factor 3 (Foxp3) and Th17 cell transcription factor retinoid related orphan receptor γt (RORγt). The differences of indicators in Treg cell transcription factor peripheral blood between the case group and the control group were compared, and the balance correlation between HMGB1 and Th17/Treg was analyzed. Results Compared with the healthy control group, the proportion of Th17 cells and the expression level of HMGB1 and IL-17 in peripheral blood of ITP patients were increased (all P < 0.01), while the proportion of Treg cells and the level of TGF-β were decreased (all P < 0.01). The proportion of Th17 cells and the expression level of IL-17 and HMGB1 in peripheral blood of ITP patients were positively correlated with the concentration of HMGB1 (all P < 0.01); the proportion of Treg cells and the level of TGF-β were negatively correlated with the expression level of HMGB1 (all P < 0.01). In vitro experiments, the expression of intracellular RORγt mRNA was increased compared with the negative control group (1.50±0.24 vs. 0.93±0.22, t = 9.612, P < 0.01), and the expression of Foxp3 mRNA was decreased compared with the negative control group after the stimulation of PBMC by rhHMGB1 (0.72±0.19 vs. 1.08±0.18, t = 7.387, P < 0.01). Conclusion The high level of HMGB1 in the peripheral blood of ITP patients induces Th17/Treg imbalance and aggravates inflammatory reactions, which may be an important cause of ITP. Key words: Immune thrombocytopenia; High mobility group box 1 protein; Th17/Treg balance; In vitro culture
{"title":"Regulatory role of high mobility group box-1 protein in the balance of Th17/Treg in peripheral blood of immune thrombocytopenia patients","authors":"Jing Yang, Jian Wang, Yaqin Mu, Xiying Wang, Lijuan Zhang, Xuping Wang, L. Diao, Wen-sheng Ge, Wenyuan Jiang, Xiaodong Wang","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.012","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.012","url":null,"abstract":"Objective \u0000To explore the effect of high mobility group box-1 protein (HMGB1) on the balance of Th17/Treg in patients with immune thrombocytopenia (ITP). \u0000 \u0000 \u0000Methods \u0000A total of 30 patients who were first diagnosed as ITP in the Fifth People's Hospital of Datong from July 2017 to April 2018 were selected as the case group, and another 30 healthy volunteers in the corresponding period were taken as the control group. The proportion of Th17 and Treg cells was detected by using flow cytometry, and the concentration of HMGB1, interleukin (IL)-17 and transforming growth factor β (TGF-β) in plasma was tested by using enzyme-linked immunosorbent assay (ELISA). Isolated peripheral blood mononuclear cells (PBMC) were cultured in vitro. After the treatment with recombinant human HMGB1 (rhHMGB1), real-time polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression changes in Treg cell transcription factor intracellular forkhead helix transcription factor 3 (Foxp3) and Th17 cell transcription factor retinoid related orphan receptor γt (RORγt). The differences of indicators in Treg cell transcription factor peripheral blood between the case group and the control group were compared, and the balance correlation between HMGB1 and Th17/Treg was analyzed. \u0000 \u0000 \u0000Results \u0000Compared with the healthy control group, the proportion of Th17 cells and the expression level of HMGB1 and IL-17 in peripheral blood of ITP patients were increased (all P < 0.01), while the proportion of Treg cells and the level of TGF-β were decreased (all P < 0.01). The proportion of Th17 cells and the expression level of IL-17 and HMGB1 in peripheral blood of ITP patients were positively correlated with the concentration of HMGB1 (all P < 0.01); the proportion of Treg cells and the level of TGF-β were negatively correlated with the expression level of HMGB1 (all P < 0.01). In vitro experiments, the expression of intracellular RORγt mRNA was increased compared with the negative control group (1.50±0.24 vs. 0.93±0.22, t = 9.612, P < 0.01), and the expression of Foxp3 mRNA was decreased compared with the negative control group after the stimulation of PBMC by rhHMGB1 (0.72±0.19 vs. 1.08±0.18, t = 7.387, P < 0.01). \u0000 \u0000 \u0000Conclusion \u0000The high level of HMGB1 in the peripheral blood of ITP patients induces Th17/Treg imbalance and aggravates inflammatory reactions, which may be an important cause of ITP. \u0000 \u0000 \u0000Key words: \u0000Immune thrombocytopenia; High mobility group box 1 protein; Th17/Treg balance; In vitro culture","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"53-56"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69843299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Refractory EB virus-associated hemophagocytic lymphohistiocytosis: report of one case and review of literature","authors":"Yin Chen, Jingtao Liu","doi":"10.3760/CMA.J.ISSN.1009-9921.2020.01.015","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1009-9921.2020.01.015","url":null,"abstract":"目的 \u0000提高对难治性EB病毒相关性噬血细胞淋巴组织细胞增生症（EBV-HLH）的临床认识和治疗水平。 \u0000 \u0000 \u0000方法 \u0000报道三门峡市中心医院2018年7月收治的1例儿童难治性EBV-HLH的临床表现、实验室检查、诊治经过，并进行相关文献复习。 \u0000 \u0000 \u0000结果 \u0000该患儿治疗开始时以积极抗感染、营养心肌、保肝等对症支持治疗，患儿病情进展迅速，对各种治疗反应差，立即予以HLH-2004化疗方案进行治疗，化疗2周仍反复发热，EBV-HLH相关指标无好转，EBV-DNA、细胞因子水平下降不明显，后因多脏器衰竭死亡。 \u0000 \u0000 \u0000结论 \u0000难治性EBV-HLH患儿起病急，病情爆发后进展迅速，病死率较高，多数患者由于EBV感染再激活所致，早期识别此类患儿，及时行造血干细胞移植是目前唯一有效的治疗手段。","PeriodicalId":16246,"journal":{"name":"Journal of Leukemia and Lymphoma","volume":"29 1","pages":"63-64"},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43145608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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