Expressions of programmed death 1 and its ligand in acute myeloid leukemia patients and their effect on anti-tumor effect of programmed death receptor 1-positive natural killer cells in vitro / 白血病·淋巴瘤

Objective:To investigate the expression of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in patients with acute myeloid leukemia (AML) and its relationship with clinical features and prognosis, and to examine its effect on PD-1-positive natural killer (NK) cells against AML cells in vitro.Methods:The bone marrow samples of 65 AML patients and the peripheral blood of 32 AML patients diagnosed in Affiliated Cancer Hospital of Zhengzhou University from July 2019 to December 2020 were prospectively collected, and the peripheral blood of 24 healthy people was taken as healthy control. The expression level of PD-L1 in bone marrow tumor cells and expression level of PD-1 in peripheral blood NK cells were detected by flow cytometry. The correlations of PD-1 expression in bone marrow tumor cells and PD-1 expression in NK cells with the clinicopathological features, curative effect and prognosis of patients were analyzed. Flow cytometry was used to detect the expression level of PD-L1 in AML cell line THP-1 (target cells) and the expression level of PD-L1 in NK cell line NKL (effector cells). THP-1 cells treated with and without 25 μmol/L of PD-L1 inhibitor fraxinellone were used as experimental group and control group, and co-cultured with NKL cells at different effector-to-target ratios. The apoptosis of THP-1 cells and the expression of NKG2D in NKL cells were detected by flow cytometry, the cell proliferation status was detected by CCK-8 and the cell proliferation inhibition rate was calculated; the levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of co-culture system were detected by enzyme-linked immunosorbent assay (ELISA).Results:The proportion of AML patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in the healthy control group [38.5% (25/65) vs. 8.3% (2/24), P = 0.029]. The proportion of AML patients with PD-1-positive expression in peripheral blood NK cells was higher than that in the healthy control group [40.6% (13/32) vs. 12.5% (3/24), P = 0.035]. There were no statistical differences in sex, age, hemogram, proportion of primordial cells, risk stratification, chromosomal karyotype, gene mutation (except NPM1 gene), fusion gene and French-American-British cooperative group (FAB) typing between patients with PD-L1 positive and negative in bone marrow tumor cells and between patients with PD-1 positive and negative in peripheral blood NK cells (all P > 0.05). In relapsed/refractory patients, the proportion of patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in newly treated patients [58.8% (10/17) vs. 31.2% (15/48), P = 0.045]. There was no significant difference in the proportion of patients with PD-1-positive expression in peripheral blood NK cells between relapsed/refractory patients and newly treated patients [(38.5% (5/13) vs. 42.1% (8/19), P = 0.837]. There was no statistical difference in complete remission (CR) rate between PD-L1 positive and negative patients [69.6% (16/23) vs. 74.3% (26/35), P > 0.05]. There was no statistical difference in CR rate between PD-1 positive and negative patients [66.7% (8/12) vs. 70.6% (12/17), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-L1 positive and negative patients [12.5% (2/16) vs. 19.2% (5/26), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-1 positive and negative patients [25.0% (2/8) vs. 16.7% (2/12), P > 0.05]. Flow cytometry showed that the positive rate of PD-1 in NKL cells was (67±6)% and the positive rate of PD-L1 in THP-1 cells was (85±5)%. After co-culture with NKL cells, the apoptotic rate and proliferation inhibition rate of THP-1 cells were higher in the experimental group compared with the control group, the expression of NKG2D on the surface of NKL cells was elevated, and the levels of IFN-γ and TNF-α in the co-culture supernatant were increased. Conclusions:In AML patients, the expression of PD-L1 in bone marrow tumor cells is high, and the expression of PD-1 in peripheral blood NK cells is also high. The expression of PD-L1 in bone marrow tumor cells of relapsed/refractory AML patients is higher than that of newly treated patients. Inhibition of PD-L1 expression in THP-1 cells can enhance the tumor killing activity of NKL cells in vitro. The mechanism may be that inhibition of PD-L1 expression in THP-1 cells up-regulates the expression of NKL cell activated receptor NKG2D and promotes the secretion of IFN- γ and TNF- α.

Progress of small molecule targeted therapy for acute myeloid leukemia / 白血病·淋巴瘤

Acute myeloid leukemia (AML) is the most common subtype of acute leukemia in adults with significant heterogeneity. Among hematological malignancies, targeted therapy for AML comes relatively late. Although traditional chemotherapy is still an indispensable part of AML treatment, more and more small molecule targeted drugs have been used in recent years since 2017. This article reviews the progress of small molecule targeted drugs for AML at the 64th American Society of Hematology annual meeting.

Safety and efficacy of upfront autologous transplantation as a consolidation therapy for progressive nasal type extranodal NK/T-cell lymphoma / 中华器官移植杂志

Objective:To evaluate the efficacy and safety of upfront autologous hematopoietic stem cell transplantation(auto-HSCT)as a consolidation therapy of progressive nasal type extranodal NK/T-cell lymphoma, (ENKL).Methods:From January 2012 to June 2021, clinical data were retrospectively reviewed for 28 patients with advanced-stage ENKL on chemotherapy of asparaginase-containing regimen followed by upfront auto-HSCT as a consolidation therapy.The median age at transplantation was 34.5(14-61)years.There were 19 males and 9 females.Clinical types were nasal(n=22)and non-nasal(n=6). Clinical stages were Ann Arbor III(n=15)and IV(n=13). Clinical risks were intermediate(n=8)and high(n=20)according to the Prognostic Index for Natural-Killer cell lymphoma-Epstein-Barr virus(PINK-E).Results:Hematopoietic reconstruction was performed.Median time of neutrophil engraftment was 10(8-17)days and 13(10-22)days for platelet.Median follow-up time was 59.5 months and 5-year OS/PFS 70.0%(95% CI: 50.60%-89.40%)and 59.1%(95% CI: 39.11%-79.10%). And 5-year cumulative recurrence and non-recurrence mortality rates were 35.42%(95% CI: 19.11%-59.39%)and 4.2%(95% CI: 2.16%-29.87%). Conclusions:Asparaginase-based chemotherapy followed by auto-HSCT is both safe and efficacious for progressive ENKTL.

Effects of autologous hematopoietic stem cell transplantation as the first-line consolidation therapy for high-risk diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the long-term efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) as the first-line consolidation therapy for high-risk diffuse large B-cell lymphoma (DLBCL) in the rituximab era.Methods:From January 2010 to June 2017, 113 DLBCL patients admitted to Henan Cancer Hospital who had complete remission (CR) after rituximab combined with chemotherapy were enrolled. Among 113 patients, 40 cases received auto-HSCT as the first-line consolidation treatment after chemotherapy (transplantation group) and 73 cases received chemotherapy only (non-transplantation group). The clinical data of 113 patients were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and OS and PFS were compared between both groups.Results:The 2-, 3- and 5-year OS rates of transplantation group and non-transplantation group were 90.0% vs. 91.8%, 84.9% vs. 80.1%, 80.9% vs. 72.8%, respectively, and the difference in OS was statistically significant of both groups ( P = 0.457); the 2-, 3- and 5-year PFS rates were 85.0% vs. 85.0%, 82.2% vs. 61.8%, 82.2% vs. 60.0%, respectively, and the difference in PFS was statistically significant of both groups ( P = 0.046). None of the patients in the transplantation group experienced early transplantation-related death. Conclusions:In the era of rituximab treatment, the first-line auto-HSCT consolidation therapy could improve the PFS of high-risk DLBCL patients who are sensitive to chemotherapy, and it may improve the OS with a good safety.

Clinical characteristics and therapeutic effect of TP53 variant in patients with acute leukemia / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL).@*METHODS@#The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed.@*RESULTS@#The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant.@*CONCLUSION@#The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.

Risk factors of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemia / 中华内科杂志

Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.

Progress of venetoclax in treatment of acute myeloid leukemia / 白血病·淋巴瘤

Venetoclax is an important breakthrough in the treatment of acute myeloid leukemia (AML) in recent years. A chemo-free treatment of inducing apoptosis drugs combined with hypomethylating agents is used in the management of AML, which brings hope of long-term survival for the elderly patients or patients who cannot tolerate intensive chemotherapy. However, there are still some patients who are resistant to venetoclax-based regimens. This article introduces the new progress of venetoclax in the treatment of AML in combination with reports at the 62nd American Society of Hematology (ASH) Annual Meeting.

Progress of myeloid-derived suppressor cells in myelodysplastic syndrome / 白血病·淋巴瘤

Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSC) within the bone marrow microenvironment. The proliferation and activation of MDSC lead to the dysfunction and depletion of natural killer cells and CD8 + T cells, and the recruitment of inflammatory cells and factors leads to the further accumulation of genetic abnormalities in MDS patients, leading to the progression of MDS. The accumulation of inflammatory cytokines in the tumor environment induces the expression of programmed death receptor 1 (PD-1) in hematopoietic stem cells and hematopoietic progenitor cells and the overexpression of programmed death receptor ligand 1 (PD-L1) in MDSC, and the interaction of PD-1/PD-L1 leads to the apoptosis of MDS hematopoietic progenitor cells and ineffective hematopoiesis. The experiments and clinical studies targeting MDSC have confirmed that correcting or reversing the bone marrow microenvironment of immune disorders in MDS is a therapeutic strategy to restore effective hematopoietic function.

New advances in targeted therapy and immunotherapy of acute myelogenous leukemia / 白血病·淋巴瘤

Acute myelogenous leukemia (AML) is a highly heterogeneous malignant hematologic disease, and it is mainly treated with traditional chemotherapy, but the efficacy is limited and the patients with worse performance status and comorbidities can not be treated with chemotherapy. Gene changes play an important role in the diagnosis and prognosis of AML, and these gene changes also provide targets for molecular targeted therapy. Meanwhlie, immunotherapy has achieved certain curative effects in AML and has a promising prospect. In this review, targeted therapy and immunotherapy of AML reported in 61st American Society of Hematology (ASH) Annual Meeting are summarized.

Analysis of efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in treatment of relapsed/refractory acute myeloid leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

New advances in targeted therapy and immunotherapy of acute myelogenous leukemia / 白血病·淋巴瘤

Acute myelogenous leukemia (AML) is a highly heterogeneous malignant hematologic disease, and it is mainly treated with traditional chemotherapy, but the efficacy is limited and the patients with worse performance status and comorbidities can not be treated with chemotherapy. Gene changes play an important role in the diagnosis and prognosis of AML, and these gene changes also provide targets for molecular targeted therapy. Meanwhlie, immunotherapy has achieved certain curative effects in AML and has a promising prospect. In this review, targeted therapy and immunotherapy of AML reported in 61st American Society of Hematology (ASH) Annual Meeting are summarized.

Pathogenic bacteria and drug sensitivity analysis of chronic suppurative otitis media and cholesteatoma in plateau area / 中国耳鼻咽喉头颈外科

OBJECTIVE To invest igate the distribution of pathogenic bacteria and the antibiotic susceptibility of otitis media in plateau areaandto guide clinical drug application rationally. METHODS Middle ear secretions were collected from 218 inpatients and outpatients(220 ears) with otitis media in our department from December 2016 to January 2018 and were performed by isolation and identification of pathogenic bacteriaand drug sensitivity test. RESULTS 1. 152 strains of microbes were isolatedincluding 125 casesof bacterial infection and 8 cases of fungal infection. 2. The gram-positive bacteria in middle ear effusions of chronic suppurative otitis media was higher than those of cholesteatoma, of which Staphylococcus aureuswas the most frequently isolated pathogen. While Pseudomonas aeruginosa was the highest in cholesteatoma. 3. The antibiotic sensitivity of pathogenic bacteria varies from strain to strain. CONCLUSION Staphylococcus aureusand Pseudomonas aeruginosa were the main pathogenic bacteria. Common pathogenic bacteria were resistance to penicillin and levofloxacin, which were commonly used in clinic. Therefore, bacterial culture should be carried out and rational drug use should be guided.

Chronic myelogenous leukemia combined with solid malignant neoplasms: report of eight cases and review of literature / 白血病·淋巴瘤

Objective To explore the clinical features of chronic myelogenous leukemia (CML) combined with solid malignant neoplasms. Methods The clinical data of 8 CML patients with solid malignant neoplasms who were admitted to the Affiliated Tumor Hospital of Zhengzhou University, the Central Hospital of Nanyang City, the First Affiliated Hospital of Science and Technology University of Henan, and the Central Hospital of Xinxiang City from August 2006 to August 2018 were analyzed retrospectively. The clinical features, treatment and prognosis of the patients were summarized with the review of literature. Results Among the 8 patients, 3 were male and 5 female, aged 40-76 years, with a median of 50 years old. Seven cases were in CML chronic phase, and 1 was in accelerated phase. Seven patients were treated with tyrosine kinase inhibitor (TKI), and only 1 patient was treated with hydroxyurea. In 8 patients, two cases presented with synchronous multiple primary cancer (SMPC), 6 cases presented with heterochrony multiple primary cancer (HMPC). two patients received the operation, 1 patient received the operation and chemotherapy, 4 patients received chemotherapy, and 1 patient received the isotope treatment. One SMPC patient died and another one was under treatment, and 6 HMPC patients were under treatment. ConclusionsThe relationship between CML and solid malignant neoplasm is under discussion, but patients with CML and solid malignant neoplasm are not unusual. Clinicians should raise awareness to avoid misdiagnosis. The treatment should follow the two main lines that are comprehensive treatment and individualized treatment.

A comparative study of unrelatedversus matched-sibling donor allogeneic hematopoietic stem cell transplantation for leukemic children / 中华器官移植杂志

Objective To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemic children .Methods Clinical data of 54 leukemic children undergoing allo-HSCT were retrospectively analyzed from May 2006 to March 2018 .According to the source of donor ,they were divided into matched sibling donor allo-HSCT group (MSD ,n = 27 ) and unrelated donor group (URD ,n= 27) .The clinical outcomes of leukemic children receiving URD allo- HSCT were assessed and those in MSD allo-HSCT group were enrolled as control .Results One patient with refractory AML was not implanted in URD group and the remaining 53 cases were successful in hematopoietic reconstitution .The time of neutrophil and platelet ,the incidence of acute graft-versus-host disease (aGVHD ) , chronic GVHD (cGVHD ) , generalized cGVHD and their transplant-related complications including pulmonary complications ,hemorrhagic cystitis between two groups were not statistically different (P> 0 .05) .The incidence of serious aGVHD ,cytomegalovirus (CMV) and EB virus (EBV) infection was significantly higher in URD group than that in MSD group (P< 0 .05) .The proportion of non-recurrent deaths in URD and MSD groups was 80％ and 31 .3％ respectively and the difference between two groups was statistically significant ( P = 0 .041) .The 3- year disease-free survival rate (DFS) of URD group and MSD group was (52 .9 ± 9 .8 )％ ,(38 .5 ± 8 .7 )％ and the overall 3-year survival rate (OS) was (57 .9 ± 9 .5)％ and (46 .5 ± 9 .7)％ respectively . The inter-group difference was not statistically significant ( P > 0 .05 ) .Conclusions In leukemic children ,although the incidence of complications post URD allo-HSCT is significantly increased , the prognosis is comparable to MSD allo-HSCT .It is a good choice when there is no suitable sibling donor .

Clinical efficacy and safety of low﹣dose decitabine subcutaneous injection combined with arsenicals in treatment of medium﹣and high﹣risk myelodysplastic syndromes / 白血病·淋巴瘤

Objective To explore the clinical efficacy and safety of low﹣dose decitabine subcutaneous injection combined with arsenicals in the treatment of medium﹣ and high﹣risk myelodysplastic syndromes (MDS). Methods Eight cases of medium﹣ and high﹣risk MDS without allogeneic hematopoietic stem cell transplantation in the Affiliated Cancer Hospital of Zhengzhou University and Xinhua Area Hospital of Pingdingshan City from January 2015 to August 2018 were retrospectively analyzed. The patients were given subcutaneous injection of low﹣dose decitabine combined with arsenicals. The specific regimen was as follow:0.1-0.2 mg/kg of decitabine, subcutaneous injection 2 times/week, 4 weeks in total; arsenic injection 10 mg/time or 0.16 mg/kg, intravenous administration, 1 time/d, 4 weeks; compound Huangdai tablets 60 mg/kg per day, 3 times orally. The efficacy and adverse reactions were observed. Results In 8 patients, there were 5 male and 3 female, with an average age of 61.4 years old (44-80 years old) Eleven cases were refractory anemia with excess blasts (RAEB), 6 cases were RAEB﹣2, 1 case was refractory cytopenia with multilineage dysplasia (RCMD) with bone marrow fibrosis (MF). Three of the patients had previously received treatment with decitabine. All patients completed the treatment successfully and no treatment﹣related deaths occurred. By the end of follow﹣up, 2 patients had complete remission, 4 patients had complete bone marrow remission with hematologic improvement, 1 patient had stable disease, and 1 patient had disease progression. For 2 patients who had been treated with decitabine regimen, the regimen of re﹣administered decitabine plus arsenic was still effective. Eight patients had more than level 2 of myelosuppression, except for one patient with intestinal infection due to unclean diet and one patient with mild pulmonary infection. The remaining 6 patients had no associated infection and heart, liver, kidney and other adverse reactions. Conclusion Low﹣dose decitabine subcutaneous injection combined with arsenicals is safe and could be a new treatment for the medium﹣ and high﹣risk MDS.

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 / 白血病·淋巴瘤

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.

Progress of immunotherapy of acute myelogenous leukemia / 白血病·淋巴瘤

Acute myelogenous leukemia (AML) is a highly heterogeneous malignant hematologic disease, and its clinical treatment mainly includes traditional chemotherapy, but the efficacy is limited and the patients with worse performance status and comorbidities can not be treated with chemotherapy. In recent years, immunotherapy has achieved certain curative effects in AML which shows a promising prospect. This review introduces immunotherapy of AML reported in 60th American Society of Hematology (ASH) Annual Meeting.

Molecular targeted therapy for acute myeloid leukemia / 白血病·淋巴瘤

In recent years, genetic alterations have played a crucial role in the diagnosis and prognostic stratification of acute myeloid leukemia (AML) and provided targeted spots for molecular targeted therapy. Due to the limitations of traditional chemotherapy, more and more targeted drugs are going to clinic or undergoing clinical trials. This article introduces several molecular targeted agents reported in the 60th American Society of Hematology (ASH) Annual Meeting.

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells combined with umbilical mesenchymal stem cells in patients with refractory severe aplastic anemia-Ⅱ / 中华内科杂志

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.

The influence of additive clonal chromosome abnormalities in Ph negative cells on the efficacy of chronic myeloid leukemia / 中华内科杂志

Objective@#To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells (CCA/Ph-) on the efficacy of chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKI) treatment.@*Methods@#The clinical data of 28 CML patients with CCA/Ph- treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively. The univariate analysis was carried out by Kaplan-Meier method. Multivariate analysis was done by Cox proportional risk model.@*Results@#A total of 28 CCA/Ph-patients were recruited including 17 males and 11 females with median age of 42.5 years old. The most common CCA/Ph-were trisomy 8 (60.7%), monosomy 7 (14.3%). 64.3% CCA/Ph-were transient and 35.7% recurrent (more than 2 times). Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients. As to the efficacy, 89.3% patients achieved major cytogenetic response (MCyR), 25% with major molecular response (MMR). The median follow-up time was 26.5 months. Treatment failure (TF) of TKI occurred in 32.1% patients with median duration of response 8 (1-41) months. Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph-and cytopenia (all P<0.05). The MMR rate was also significantly correlated with cytopenia (P<0.05). Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate (RR=3.868, 95%CI 1.216-12.298, P=0.022) .@*Conclusions@#Cytopenia in CCA/Ph-appears to be an independent risk factor of MMR in CML patients with TKI treatment. The recurrent CCA/Ph-may link to higher treatment failure rate. Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.