Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma / 中华血液学杂志

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents / 中国实验血液学杂志

OBJECTIVE@#To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment.@*METHODS@#The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse.@*RESULTS@#170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（P<0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（P=0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse.@*CONCLUSION@#The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

Analysis on Clinical Characteristics and Prognosis of 47 Patients with Extranodal NK/T Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and prognostic factors of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of patients with ENKTL from November 2009 to November 2019 was collected and retrospectively analyzed to clarify the clinical features of ENKTL, and evaluate the factors that affected survival and prognosis.@*RESULTS@#Forty-seven patients with ENKTL were collected, median age was 40 (12-82) years old, and more common in males than females, at the ratio of 1.47∶ 1. The median follow-up was 28 (1-112) months, and 5-year overall survival (OS) rate was 49.3%. The 5-year OS rates of the subjects with ECOG performance stage 0-1 and ≥2 were 51.6% and 0 (P=0.001), respectively. The 5-year OS rates of International Prognostic Index (IPI) score 0-1 and ≥2 were 60.0% and 40.6% (P=0.027), respectively. The 5-year OS rates of Ann Arbor staging Ⅰ/Ⅱ and stage Ⅲ/Ⅳ were 61.3% and 31.7% (P=0.005), respectively. The 5-year OS rates of the patients with presentation of B symptoms and without presentation of B symptoms were 79.0% and 30.1% (P=0.013), respectively. The 5-year OS rates of plasma EBV-DNA level < 5×10@*CONCLUSION@#ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens are independent prognostic factors for OS of patients with ENKTL.

Clinical Characteristics and Prognosis Affecting-Factors of the Patients with Burkitt Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and treatment outcome of patients with Burkitt lymphoma.@*METHODS@#The clinical data of 27 patients with Burkitt Lymphoma were collected and retrospectively analyzed, the clinical characteristics, laboratory data, survival and the factors affecting the prognosis were also analyzed.@*RESULTS@#Among the 27 patients (mainly for adults), the median age was 30 (15-83) years old, the ratio of male and female was 3.5∶1. There was no EB virus infection in all the patients, 92.6% of the patients showed extranodal organs involvement, 40.7% of them were leukemic stage, 85.2% patients belonged to Ⅲ and Ⅳ stage, 74.1% patients belonged to high/high-middle risk according to IPI index. In the terms of molecular biology, five patients were treated with next-generation sequencing test, and the MYC gene mutations were detected out in alt the patients, and the most common mutations were CCND3, ID3 and TP53. The overall response rate (ORR) for all the patients was 85.2%, the complete response (CR) rate was 63.0%, and the partial response rate was 22.2%, the 5-year progression-free survival rate and overall survival rate of the patients was 76.6% and 76.6%, respectively, which showed that the efficacy of the patients in high-dose methotrexate treatment group was higher than that in the non-high high-dose methotrexate treatment group. For the patients treated with LMB89 chemotherapy, the CR was 78.6%, ORR was 100%, the 5-year survival rate was 92.9%, which was superior to the patients treated with other regimens. Auto-hematopoietic stem cell transplantation as consolidation treatment could improve the prognosis for those patients who could not tolerate high-dose chemotherapy. Univariate analysis showed that ECOG score, the level of LDH>500 U/L, WBC level, CNS involvement, short-term effect and LMB89 regimen were the risk factors affecting the prognosis of the patients.@*CONCLUSION@#The adult Burkitt lymphoma are highly aggressive. For the patients in high-dose methotrexate treatment group, especially LMB89 regimen can improve the survival of the patients, and to choose HSCT as a consolidation treatment can be a choice for those patients who could not tolerate high-dose chemotherapy.

Inhibitory Effect of S1PR2 Antagonist JTE-013 on Proliferation of Chronic Myeloid Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of sphingosine-1-phosphate receptor 2 (S1PR2) specific antagonist JTE-013 on the proliferation of human chronic myeloid leukemia (CML) cell line K562.@*METHODS@#K562 cells were treated with JTE-013 (0, 0.5, 1, 5, 10, 20 μmol/L) for 24 and 48 hours respectively, CCK8 assay was used to detect the cell viability. K562 cells were treated with JTE-013 (0, 5, 10, 20 μmol/L) for 24 hours, propidium iodide (PI) DNA staining was used to analyze the cell cycle, Western blot was used to determine the levels of P21 and Cyclin D1 protein expression.@*RESULTS@#JTE-013 inhibited the proliferation of CML cell line K562 in a dose dependent manner (r=-0.971). The proliferation rate of CML cells showed that the activity of CML cells decreased gradually with the increase of JTE-013 concentration (r=-0.971). The detection demonstrated that JTE-013 suppressed tumor cell proliferation through cell cycle arrest in G/G phase. Further detection of the protein expressions of G phase regulators showed that level of P21 increased, and expression of Cyclin D1 decreased.@*CONCLUSION@#JTE-013, a S1PR2 antagonist, can inhibit the proliferation of human CML K562 cells, which may be achieved by arresting the cells in G/G phase.

Clinical Efficacy of Allo-HSCT on FLT3-ITD Positive AML Patients / 中国实验血液学杂志

OBJECTIVE@#To detect the expression levels of FAM19A5 in patients with mantle cell lymphoma (MCL), and to determine the relationship between FAM19A5 and the prognosis of MCL patients.@*METHODS@#Twenty-five MCL patients were choosen in the study, cytometric bead assay was used to detected the concentration of FAM19A5 in serum and immunohistochemical analysis were used to detect the expression levels of FAM19A5 in lymph nodes. The relationship of the FAM19A5 expression in serum and tissue were analyzed, the relationship of FAM19A5 and clinical characteristics of MCL patients, treatment and prognosis of MCL patients was analyzed.@*RESULTS@#The average serum concentration of FAM19A5 in MCL patients was 90.55±38.24 (ng/ml), which was significantly higher than that in control (P=0.0461). The proportion of high, medium, and low expression of FAM19A5 in lymph nodes was 32%, 36% and 32%, respectively, which showed significant difference from that in control group (P=0.001). The expression of FAM19A5 in serum and lymph nodes showed significant correlation (r=0.8683，P=0.001). The serum concentration of FAM19A5 showed positive correlation with the proportion of Ki67 (P=0.0222, r=0.4554). The mean survival time without relapse/death of MCL patients with high, middle and low expression of FAM19A5 was 17, 27 and 37.5 months, respectively，which showed significant statistical difference (P=0.0360). ROC curve analysis showed that serum concentration of FAM19A5 could predict the therapeutic effect in MCL patients, the cut-off value was 91.49 ng/ml. The proportion of recurrent/death in AML patients with FAM19A5 ＞91.49 ng/ml was significantly higher than that in patients with FAM19A5＜91.49 ng/ml (P=0.0156).@*CONCLUSION@#The expression level of FAM19A5 is increased in MCL patient, and patients with high expression of FAM19A5 are more likely to relapse or die. FAM19A5 may be a new prognostic marker and potential therapeutic target for MCL.

Detection of BCR/ABL Fusion Gene and ASS1 Gene Deletion by Using Tricolor Dual-fusion Probe / 中国实验血液学杂志

OBJECTIVE@#To analyze the significance of various abnormal signal patterns appreared in CML and B-ALL patients by using BCR/ABL/ASS1 tricolor dual-fusion probe, and to explore its application value in detecting BCR/ABL fusion gene and ASS1 gene deletion.@*METHODS@#50 newly diagnosed CML patients and 50 newly diagnosed B-ALL patients were detected by fluorescence in situ hybridization (FISH) with BCR/ABL/ASS1 tricolor dual-fusion probe. Meanwhile, karyotype analysis was performed on all the patients using the 24 hours short-term culture and R-banding.@*RESULTS@#Among the 50 CML patients, Ph was found in 49 cases, 5 normal interphase karyotype was observed in 1 case. FISH detection showed that BCR/ABL fusion gene existed in all patients (100%), while the positive signal pathway showed that 1R1G2B2F was observed in 39 cases (78%), 2R1G2B1F in 2 cases (4%) and 1R1G2B1F in 6 cases (12%), simultaneous existence of 1R1G1B1F and 1R1G2B3F in 1 case (2%), 2R1G1B1F in 1 case (2%) 1R1G3B3F in 1 case (2%). FISH detection also showed that the karyotype of 6 case at ASS1 gene deletion (1R1G1B1F) all were simple t (9; 22) translocation, and other abnormalities not were observed. Among 50 cases of B-ALL, Ph was found in 13 cases, the numerical aberration and structural aberration of non t (9; 22) in 16 cases, normal karyotype in 20 cases, absence of mitotic phase in 1 case. FISH detection showed that 16 cases (32%) had BCR/ABL fusion gene including 13 cases (26%) of 1R1G2B2F, 1 case (2%) of stimultaneous exitance of 1R1G2B2F and 1R1G3B3F 1 case (2%) of 2R1G1B1F, 1 case (2%) of 1R1G3B2F. FISH detection also showed that 3 cases had BCR/ABL fusion gene, including 1 case with ASS1 gene deletion (2R1G1B1F), 1 case with classical t (9; 22) translocation (1R1G2B2F) and 1 case with BCR/ABL fusion gene and increase of ASS1 gene copy (1R1G3B3F).@*CONCLUSION@#Tricolor dual-fusion FISH probe for detecting BCR/ABL fusion gene and ASS1 gene deletion is simple, rapid, sensitive and stable. It can detect various forms of molecular fusion and avoid the false positive results due to coincidental overlap of signals generated by D-FISH probe and ES-FISH probe. In addition, this detection method not only can directly observe the presence or absence of ASS1 gene deletion, but also improve the reliability of the positive results of newly diagnosed BCR/ABL fusion gene and accuracy of monitoring results of minimal residual disease for the subsequent visit.

Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19 / 北京大学学报(医学版)

OBJECTIVE@#To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19).@*METHODS@#Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups.@*RESULTS@#The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and NK cells, CD4+/CD8+ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8+ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8+ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs. 19 : 21 : 0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant (P=0.043).@*CONCLUSION@#The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

Clinical Characteristics and Prognosis of 84 Elderly Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the prognostic factors of elderly AML patients, as well as the application and prognostic value of comprehensive geriatric assessment（CGA） in elderly AML patients in China, so as to determine a suitable comprehensive assessment method that can predict survival and guide treatment of patients in Chinese people.@*METHODS@#Retrospective analysis was performed on the medical records of 84 AML patients aged over 60 years old, and diagnosed in our department from October 2007 to December 2017, and the clinical, pathological and comprehensive evaluation of related prognostic factors was analyzed.@*RESULTS@#The median age of all patients was 70 (60-91) years old, ratio of male to female was 1.9∶1 (55∶29) , the median OS time was 9 (1-125) months, 1 year OS rate was 35.3%, and 5 year OS rate was 12.6%. The age grouping, remission of induction chemotherapy, whether refractory/relapse, WBC count grouping at initial diagnosis, levels of lactate dehydrogenase and creatinine were risk factors for OS. Remission of induction chemotherapy, whether refractory/relapse, WBC count grouping and co-infections at initial diagnosis, levels of lactate dehydrogenase, and ECOG score were the risk factors for DFS. In the assessment of comorbidities, the two score classifications of charlson comorbidity index(CCI) were the risk factor of OS, however,whose effects for DFS were not statistically different. The effects of 3 score classifications of hemaotopoietic cell transplantation comorbidity index (HCT-CI), 4 score classifications of comulative illness kating scale for geriatrics (CIRS-G) and 3 score classifications of CIRS-G on OS and DFS were not statistically different. The impact of the ACA index on OS and DFS was statistically significant in elderly patients. All indexes related with patients self factors and disease-related factors were no independent prognostic factors for OS and DFS, so the judgment of prognosis needs to be comprehensively evaluated.@*CONCLUSION@#The prognosis and treatment selection of elderly AML patients should be combined with traditional clinical and pathological prognostic factors as well as comprehensive assessment of the elderly patients.

Expression and Clinical Significance of CXCR3 in Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of chemokine receptor CXCR3 in mantle cell lymphoma (MCL).@*METHODS@#Flow cytometry was used to detect CXCR3 in lymph nodes and extranodal tissues in 25 newly diagnosed MCL patients. The correlation of the expression of CXCR3 level with clinical features and prognostic factors was analyzed.@*RESULTS@#Twenty-five tumor submitted specimens all expressed CXCR3 at varied degrees. The expression levels of CXCR3 in lymph nodes (LN) and bone marrow (BM) were higher than those in peripheral blood (PB), and the expression intensity in BM positively correlated with the involved tumor numbers. The absolute values of lymphocytes and hemoglobins level in PB of CXCR3high group were significantly lower than those in CXCR3low group (all P0.05). The overall response rate (ORR) in CXCR3low group was significantly higher than that in CXCR3high group (P=0.001). The expression level of CXCR3 in MCL cells of the effective group was significantly lower than that before treatment (P=0.038), and the CXCR3 expression in the ineffective group was significantly higher than that before treatment (P=0.002). After following up, it was found that the 3-year overall survival (OS) time and progression-free survival (PFS) time in CXCR3high group were significantly shorter than those in CXCR3low group (all P<0.05).@*CONCLUSION@#The expression level of CXCR3 in MCL closely relates with early metastasis and prognosis. CXCR3 can be used as one of the indicators for clinical efficacy and prognosis evaluation.

Efficacy of anti-CD19 CAR-T cell therapy in 10 refractory recurrent B cell malignancies / 中华血液学杂志

Objective: To investigate the outcomes of anti-CD19 CAR-T cell for relapsed and refractory B cell malignancies. Method: Ten patients with relapsed and refractory B cell acute lymphocytic leukemia (B-ALL) and non-Hodgkin's lymphoma (NHL), diagnosed in the Department of Hematology of Peking University third Hospital from December 2015 to July 2017, were treated with anti-CD19 CAR-T cell therapy, and the efficacy and safety were analyzed. Results: Efficacy was assessed on the 28th day after cell infusion, including 66.7% (4/6) of complete remission (CR) for patients with ALL, 16.7% (1/6) of partial remission (PR), and 83.3% (5/6) of overall response rate (ORR). For NHL patients, CR was 33.3% (1/3) and most of the lesions disappeared in a patient with mantle cell lymphoma, but residual lesion presented persistent state. After infusion of anti-CD19 CAR-T cells, the main side effect was cytokine release syndrome (CRS) and fever. One patient presented with aphasia and the other one had multiple organ failure, which were improved after treatment. No patients died of CRS. Conclusion: anti-CD19 CAR-T cell for relapsed and refractory B cells hematological malignancies is safe, and the most problematic side effect is CRS, which can be controlled by therapy.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia with FLT3-ITD Mutation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of acute myeloid leukemia(AML) patients with FLT3-ITD(Fms-like tyrosine kinase3, intenal tandem duplication) mutation and their response to treatment.</p><p><b>METHODS</b>Retrospective analysis of 128 newly diagnosed AML (except type M3) patients was performed between January 2014 and July 2017. Patients were divided into FLT3-ITD mutated group and non-mutated group. Mutation detection was carried out by using polymerase chain reaction(PCR) and gene sequencing analysis. Standard 3 + 7 or CAG regimen were taken as the first induction chemotherapy, 4 cases received sorafenib, overall survival (OS) was calculated by Kaplan-Meier.</p><p><b>RESULTS</b>Ninety-seven patients can be evaluable for clinical data available; 4 patients were FLT3-TKD mutated, which accounted for 4.1%; 19 patients were FLT3-ITD mutated, which accounted for 19.59%(19/97). Median white blood cell count (WBC), percentage of peripheral blasts and LDH value were significantly higher in FLT3-ITD group than those in non-mutated group [64.65(1.07-587.92)×10/L vs 39.68 (0.45-203.81) ×10/L](P<0.01), [69.62(16-99)% vs 36.35(0-92) %](P<0.01 ) and [LDH 526(124-2 729)U/L vs 265(20-1977)U/L](P<0.05), respectively. The frequency of coexisting NPM1 mutation was higher in FLT3-ITD group than that in non-mutated group [36.8(7/19)% vs 6.8 (5/74) %](P<0.01). The CR+PR was lower in FLT3-ITD group than that in non-mutated group [31.6(6/19)% vs 64.9 (48/74)%](P<0.05). OS in FLT3-ITD group was significantly shorter than that in non-mutated group (5 vs 18 months)(P<0.05). There is no significant difference in OS between FLT3-ITD concomitant with and without NPM1 mutation groups(5 vs 5 months)(P>0.05). The median OS was 13 months for the FLT3-ITD patients taking sorafenib.</p><p><b>CONCLUSION</b>The FLT3-ITD is a common mutation in AML, FLT3-ITD mutated AML is more likely concomitant with NPM1 mutation with higher number of WBC, percentage of peripheral blasts and LDH value, thus CR is low after the 1st treatment and survival is poor.</p>

Application of CD19-CAR T Cells in Refractory Relapsed Acute B Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of CD19-targeted chimeric antigen receptor T-cell (CD19-CAR T) in the treatment of patients with refractory relapsed B cell acute lymphocyte leukemia（B-ALL）.@*METHODS@#The efficacy and safety of CD19-CAR T cells in treatment of patients with refractory relapsed B-ALL from January 2015 to July 2017 in the Department of Hematology of Peking University Third Hospital were analyzed retrospectively.@*RESULTS@#A total of 10 patients were included in this analysis, all of which were consistent with the diagnosis of refractory relapsed B-ALL, and the immunophenotype of leukemia cells was CD19 positive. After treatment with CD19-CAR T cells, the overall response rate（ORR） on day 28 was 70%. Among them, 6 cases reached complete remission（CR）, 1 case reached partial remission（PR）. The rate of CR on day 90 was 30%.@*CONCLUSION@#CD19-CAR T cells are effective in the treatment of refractory relapsed B-ALL, and the adverse reactions are controllable.

Clinical Features, Treatment and Prognostic Factors of 94 Patients with Follicular Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestation, therapeutic efficacy and related prognostic factors of patients with follicular lymphoma.</p><p><b>METHODS</b>A retroretrospective study was conducted on 94 patients with follicular lymphoma who were admitted to our hospital from March 1999 to June 2016. The total of 94 newly diagnosed FL patients were analyzed in terms of clinical manifestation, laboratory data, pathological examination, clinical stage and so on, so as to find out the related prognostic factors.</p><p><b>RESULTS</b>Ninety-four patients were included in this study. The median age at onset was 50.60 years old, more common in women, and ratio of male to female was 1:1.35. The superficial lymphadenopathy was found to be the first symptom in 72.3% patients, 25.5% patients had B symptoms when diagnosed, 57.4% cases had extranodal organ invasion when diagnosed, of which bone marrow invasion is the most common, accounting for 36.2%, followed by the digestive tract, bone, spleen and so on. The detected rate of BCL-2 / IGH gene rearrangement was 33.9%. Patients with grade 3 of FL accounted for 24.5%. Cases of clinical stage III-IV accounted for 71.2% in these FL patients. The overall response rate (ORR) was 92.0%, and the complete remission (CR) rate was 79.3% and the recurrence rate was 35.2%. The cumulative overall survival rates of 3, 5 and 10 years were 92.1% , 84.6% and 77.4% respectively, and the cumulative progression-free survival(PFS) rate in 3,5 and 10 years was 68.5%, 61.4% and 41.9%, respectively. The results showed that the CR rate was 85.2% in patients treated with rituximab and 69.7% in patients treated without rituximab. The OS and PFS in patients treated with rituximab were better than those in patients treated without rituximab, but there was no significant difference between them(P>0.05). Univariate analysis showed that FL stage, ECOG score, Hb and LDH levels, digestive tract involvement or not, CR or not after initial treatment had a significant impact on OS(P<0.05), while BCL-2, CD10, ECOG score, albumin, Hb and LDH levels, percentage of lymphocytes, erythrocyte sedimentation rate, digestive tract involvement had a significant impact on PFS (P<0.05). Multivariate analysis showed that digestive tract involvement or not, CR or not after initial treatment were independent risk factors for OS(P<0.05), while CR or not after initial treatment, digestive tract invdvement or not, LDH level and ECOG score were independent risk factors for PFS(P<0.05).</p><p><b>CONCLUSION</b>The FL is more common in middle-aged women, the FL was in late stage at confirmed diagnosis, bone marrow involvement is more common. The CD10 negative is poor prognostic factor for FL. The digestive tract involvement or not, CR or not after initial treatment are independent risk factors for OS, while CR or not after initial treatment, digestive tract involvement or not, LDH level and ECOG score are independent risk factors for PFS.</p>

Relationship of the Changes of Peripheral Blood Immuno-Cell Subsets with the Prognosis of B Cell Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship of T lymphocyte subsets, B lymphocytes and NK cells with the genesis, progression and prognosis of B cell lymphoma.@*METHODS@#The levels of T lymphocyte subsets, B lymphocytes and NK cells in peripheral blood of healthy control group and B cell lymphoma group were detected by flow cytometry (FCM). The clinical data were collected, and the relationship of these immune indexes with the general conditions, laboratory indexes, curative effect and prognosis were analyzed.@*RESULTS@#Forty-four patients entolled in this study including 24 male and 20 females with the median age of 57 years old (17-82 years), all the patients were the first visit to our hospital and diagnosed. The total counts of lymphocytes, T, B and NK cells in the peripheral blood of patients with the first treatment of B-cell lymphoma were significantly lower than those in healthy controls, and the ratio of CD3HLA-DR activated T cells was significantly higher than that of healthy controls ( 61.5 /μl was higher than that in patients with low level of NK cells.@*CONCLUSION@#The level of total lymphocytes, total T cells, total B cells, NK cells and advanced activated T cells in the patients with B cell lymphoma were significantly different from those in normal subjects. Total count of lymphocytes, T cells, B cells, CD4 cells and NK cells in peripheral blood are important prognostic indicators for BCL. The ECOG score and β2-microglobulin level are independent risk factors for prognosis. The NK cell level and FAC-1 are independent protective factors for the prognosis of B cell lymphoma.

Analysis of Clinical Characteivstics and Therapeutic Efticacy of 54 Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical characteristics and therapeutic efticacy of patients with mantle cell lymphoma(MCL).</p><p><b>METHODS</b>The clinical data including cliniced parameters and laboratorial test results of 54 patients with MCL were collected and restrospectively analyzed to clarity the clinical characteristics of MCL and to evaluate the survival and factors affecting prgnosis of patients.</p><p><b>RESULTS</b>The incidence of MCL accounted for 4.0% of NHL in our center. The median age of MCL patients was 63 years old, the male and female ratio was 1.4∶1. The MCL patients inⅢ-Ⅳ stage accounted for 96.3%; the extranodal organ involvement existed in 98.1% patients, the most common extranodal involvement sites were bone marrow(72.2%), spleen(51.9%), gastrointestinal tract(25.9%). The overall response rate(ORR) was 66.7%, among which the complete remisson (CR) rate was 37.1%, 3 year and 5 year-progression free survival rate was 52.7% and 34.7% respectively, 3 year and 5 year overall survival rate was 60.4% and 49.6% respectively. The therapeutic efficacy in chemotherapy combined with cytarabine group was suprior to that in chemotherapy group without cyteratine, the chemotherapy comtined with auto-HSCT could further improve the prognosis of patients. The unvariatc analysis showed that the KI67 level, B sgmptom, liver function, LDH and C-RP levels, initial therapeutic efficacy, high dose cytarabine regimen, auto-HSCT and relapse-refractroy status were prognosis-related factors; the multi-variate analysis showed that the initial therapeutic efficacy and relapse rcfractory stasus were independent prognostic risk factors. Analysis showed that the surival of patients stratified according to MIPI and MIPI-c indexes was significantly different from that stratified by IPI index.</p><p><b>CONCLUSION</b>The MCL patients commonly complicated by extranodal involvement and have poor prognoss. Using the chenotherapy regimen combined with high doge of cytarabine as induction therapy and auto-HSCT as consotidatory therapy shows the significont efficacy for survival of young patients with MCL. The MIPI and MIPIc indexe are more much suitable for prognosis evaluation of MCL patients.The initial therapeuntic efficacy and relapse-refractrong status are the independant prognosis-related factors.</p>

Research Progress of Cell Immunotherapy in Treatment of Hematological Malignancies-Review / 中国实验血液学杂志

Cell immunotherapy, as an important mean of tumor therapy, infuses a large number of immune effector cells amplified in vitro to the patients, resulting in the anti-tumor effect. There have been a series techniques of cell immunotherapy, including T lymphocyte therapy, dendritic cell-based immune cell therapy, natural killer cell therapy, gamma delta T cell therapy and so on. The preparation and culture conditions, anti-tumor mechanism, target cells etc of these immune cells are not the same, the each with its advantages and disadvantages. Many clinical studies have showed that the patients with a variety of tumors including hematological malignancies, who adopted cell immuno-therapy, had the prolonged survival, an improved quality of life, and with the less adverse reactions. This review summarizes the available data on the characteristics of different cell immunotherapies and their application in hematological malignancies.

Clinical Features and Response to Treatment in Newly Diagnosed Multiple Myeloma Patients with Deletion 17P / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and response to therapies in multiple myeloma (MM) patients with del (17p).</p><p><b>METHODS</b>A total of 122 newly diagnosed MM patients hospitalized in the Department of Hematology of Peking University Third Hospital between October 2012 and September 2016 were analyzed retrospectively. The fluorescent in situ hybridization(FISH) and G-binding staining were used for detection of cytogenetic abnormalities. These MM patients with del (17p) were divided into non-bortezomib chemotherapy (VAD or CHOP) group and bortezomib chemotherapy (PAD or PCD) group. Response criteria was according to IMWG criteria, including complete remission (CR), very good partial remission (VGPR), partial remission (PR), stable disease (SD), overall response rate (ORR) was defined as CR+VGPR+PR. The Kaplan-Meier method was used to evaluate overall survival (OS) and progressive free survival (PFS).</p><p><b>RESULTS</b>Cytogenetic abnormalities were detected in 60 patients, and the frequency of del(17p) was 10.7% (13 of the 122 patients). For the 13 MM patients with del(17p), median age was 59 years old, male vs female ratio was 8:5, 7 patients were found to have soft tissue plasmacytoma at the time of diagnosis, and IgG accounted for 61.5% (8/13). The frequency of coexisting other cytogenetic abnormalities was 53.8% (7/13); del(13q14) (D13S319 and/or RB1) accounted for 30.8%(4/13), and gain (1q21) 23.1%(3/13), 13 patients were able to be evaluated for the response, ORR were 33.3%(2/6) vs 100.0%(7/7), VGPR 0% vs 57.1%, PR 33.3% vs 42.9%, PD 50.0% vs 0% in non-bortezomib chemotherapy and bortezomib groups, respectively (P=0.042). 4 patients received 50 Gy radiotherapy for soft tissue plasmacytoma, no responses were observed. With a median follow up of 14(2.0-40)months, median PFS and OS time were 6(95% CI0.9-11.1) months and 21(95% CI9.0-33.0) months, respectively. Median OS in bortezomib groups was significant longer than that in the non-bortezomib groups, not reachable vs 10.8(95%CI3.4-16.6) months (P=0.017).</p><p><b>CONCLUSION</b>MM with del(17p) shows high frequency of soft tissue plasmacytoma, and high prevalence of coexisting gain(1q21) and del(13q14). These patients are not sensitive to non-bortezomib chemotherapy or radiotherapy, and has a poor survival. Bortezomib are able to improve the outcome of these MM patients.</p>

MicroRNA-223 Regulates the Differentiation of Human Embryonic Stem Cells to Dendritic Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish a new inducing system for differentiation of human embryonic stem (ES) cells to dendritic cells (DC), and further explore how microRNA-223 (miR-223) regulates DC differentiation from ES cells.</p><p><b>METHODS</b>Human ES cells were cultured on plates coated by IV type collagen and differentiated into hematopoietic stem/progenitor cells, common myeloid progenitor cells and DC step by step via adding different hematopoietic growth factors. The differentiated cells were identified by morphology, flow cytometry and hematopoietic colony forming unit (CFU) assays. Human ES cells were transfected with lentiviral vectors to overexpress miR-223 or inhibit miR-223 expression, then initiated the differentiation to DC. The differentiated cells at the different miR-223 levels were compared by the numbers of hematopoietic CFU and the expressions of specific surface markers. Dual-luciferase reporter assay was performed to test whether miR-223 directly targets TGFBR3.</p><p><b>RESULTS</b>Human ES cells were successfully induced into DC as the percentage of CD83 was approximately 82%, and the expression of miR-223 was up-regulated during the whole process. Supplementing miR-223 level using synthetic miR-223 mimics improved the proportions of CD34CD45, CD34CD45and CD83in differentiated cells, which were significantly higher than those in synthetic miR-223 inhibitor group and negative control (P<0.05). The expressions of cell makers at each differentiated phase in miR-223 inhibitor group were significantly lower than those in negative control (P<0.05). The differentiated cells in miR-223 mimics group showed approximately 759 CFUs per 10cells, which was significantly higher than that in others (P<0.05). Compared with negative control, miR-223 substantially inhibited the luciferase activity of Tgfbr3 3'UTR construct (by 37%) (P<0.05). In addition, the luciferase activity of the mutant construct was significantly higher than that of the WT construct in the presence of miR-223 mimics (P<0.05). With DC mature, the protein level of TGFBR3 gradually decreased using miR-223 mimics, and increased in miR-223 inhibitor group due to the suppression of the endogenous miR-223.</p><p><b>CONCLUSION</b>MiR-223 promotes the differentiation of human ES cells to DC, probably through direet target to TGFBR3.</p>