Progress of immune checkpoint inhibitors in extranodal NK/T cell lymphoma / 白血病·淋巴瘤

Extranodal NK/T cell lymphoma (ENKTCL) is a group of highly aggressive non-Hodgkin lymphoma associated with epstein-barr virus infection. Asparaginase-based chemoradiotherapy regimens are not effective in advanced patients. In recent years, anti-programmed-death receptor 1 (PD-1)/programmed-death receptor ligand 1 (PD-L1) immunotherapy has developed rapidly, which can effectively improve the prognosis of ENKTCL patients. But some patients with ENKTCL still have low response rate. This article reviews the mechanisms of resistance to anti-PD1/PD-L1 therapy and other immune targets in ENKTCL recently to change the traditional treatment mode of ENKTCL through the combination of different targeted drugs.

Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT) / 白血病·淋巴瘤

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Correlation between SLAMF6 expression and perforin and granzyme B on circulating CD8 +T cells and the clinical significance in patients with severe aplastic anemia / 中华检验医学杂志

Objective:To explore the correlation between the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) on peripheral blood CD8 +T cells and perforin and granzyme B and the clinical significance in patients with newly diagnosed severe aplastic anemia(SAA). Methods:The indicators of blood routine and bone marrow and peripheral blood samples of 32 newly diagnosed SAA patients admitted to Henan Provincial People′s Hospital from January 2016 to June 2019 were collected for retrospective analysis. Flow cytometry was used to detect the expression of SLAMF6, perforin and granzyme B on samples CD8 +T cell before therapy and 6 months after therapy (11 cases received transplantation, 21 cases received immunosuppressive therapy [IST]). Spearman correlation analysis was performed to determine the association between clinical indicators and laboratory test results. The expression of SLAMF6, perforin and granzyme B was also detected in 10 healthy people (normal group) and 13 myelodysplastic syndromes/paroxysmal nocturnal hemoglobinuria (MDS/PNH) patients (MDS/PNH group). Results:(1) At diagnosis: the expression of SLAMF6 was significantly lower in the SAA group than that in the normal group and the MDS/PNH group ([56.40±6.37]% vs [84.34±5.81]% and [82.24±4.98]% (both P<0.001]). The expression of perforin was significantly higher in the SAA group (32.73±8.46) than that in the normal control group (23.75%±5.10%), and the MDS/PNH group (26.12%±5.53%) (both P<0.05). The expression of granzyme B was also significantly higher in the SAA group (36.23%±7.94%) than that in the normal control group (21.67%±5.05%) and the MDS/PNH group (21.79%±5.10%) (both P<0.001). The expression of SLAMF6 was positively correlated with the hemoglobin ( r=0.804), and reticulocyte absolute values ( r=0.656) in peripheral blood, percentage of granulocytes ( r=0.643) and erythrocytes ( r=0.622) in bone marrow of SAA patients (all P<0.05). Expression of SLAMF6 was negatively correlated with perforin ( r=-0.792) and granzyme B ( r=-0.908) on CD8 +T cells in patients with SAA (both P<0.001). (2) After treatment: the expression of SLAMF6 in peripheral blood CD8 +T cells of 30 surviving patients was higher than pre-treatment ([79.19±12.69]% vs [56.40±6.37]%, P<0.001). The expressions of perforin and granzyme B were lower than pre-treatment level (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 11 transplanted patients was higher than before transplantation ([86.54±3.75]% vs [56.40±7.35]%, P<0.001). The expressions of perforin and granzyme B were lower than before transplantation (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 12 IST-respond patients was higher than that before treatment, while the perforin and granzyme B levels were lower than pre-treatment (all P<0.05). The post-treatment expressions of SLAMF6, perforin and granzyme B were similar as before treatment levels in 7 IST-unrespond patients (all P>0.05). Conclusion:SLAMF6 is significantly down-regulated on CD8 +T cells in newly diagnosed SAA, negatively correlated with the effective factors of CD8 +T cells, which might participate in the immune regulatory of CD8 +T cells as a negative regulatory factor in patients with SAA. The SLAMF6 is significantly up-regulated after hematopoietic recovery, while there is no significant change in treatment-unrespond patients, which could thus serve as an useful diagnostic and therapeutic index of patients with SAA.

Clinical study on factor Ⅷ inhibitor in children with hemophilia A / 中华血液学杂志

Objective@#To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) .@*Methods@#Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018.@*Results@#A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) .@*Conclusions@#Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

Progress of TIM-3, BTLA and LAG-3 in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Diffuse large B-cell lymphoma (DLBCL) is the most common invasive non-Hodgkin lymphoma, which responds well to R-CHOP regimen immunochemotherapy, but 30%-40% of the patients eventually develop relapsed and refractory DLBCL. Therefore, the discovery of new prognostic markers is essential to improve the diagnosis and treatment of DLBCL. Immune escape is an important mechanism for the occurrence and development of DLBCL. Studies have shown that TIM-3, BTLA and LAG-3 are highly expressed in DLBCL, which could inhibit the effective function of immune cells in tumor microenvironment, and promote the immune escape of lymphoma cells. Thus, they promote the occurrence and development of DLBCL and affect the effect of conventional chemotherapy. It is important to explore the effects of the above three inhibitory molecules on DLBCL, and they are expected to become new targets for the treatment of DLBCL.

Expression of CD45 in newly diagnosed multiple myeloma and the relationship with prognosis / 中华血液学杂志

Objective@#To explore the expression of CD45 in newly diagnosed multiple myeloma (MM) and its relationship with clinical efficacy and prognosis.@*Methods@#This study retrospectively analyzed expression and distribution of CD45 in 130 cases of newly diagnosed MM, comparing clinical efficacy and prognosis in CD45+/CD45- groups.@*Results@#①The CD45+ group was 33 cases (25.38%) , and CD45- group was 97 cases (74.62%) . ②The objective remission rate (ORR) of CD45+ and CD45-group was 33.33% and 64.95%, respectively. The difference was statistically significant (P=0.002) . For patients in Bortezomib regimen, the ORR of CD45+ and CD45- group was 35.71% and 66.25%, respectively. The difference was statistically significant (P=0.005) . ③The median progress free survival (PFS) of CD45+ group and CD45- group was 29.8 (95%CI 10.0-59.0) months vs 34.5 (95%CI 6.0-69.0) months (χ2=14.59, P<0.001) and the median overall survival (OS) was 32.5 (95%CI 10.0-68.0) months vs 37.6 (95%CI 6.0-78.0) months (χ2=11.42, P=0.001) , respectively. Among the patients in bortezomib regimen, The median PFS and median OS of CD45 + group and CD45- group were 30.3 (95%CI 10.0-59.0) months vs 36.3 (95%CI 6.0-69.0) months (χ2=14.75, P=0.001) and 34.0 (95%CI 10.0-68.0) months vs 39.5 (95%CI 6.0-78.0) months (χ2=10.62, P=0.001) . ④Cox risk regression model analysis showed that serum creatinine≥176.8 μmol/L (HR=5.078, 95%CI 1.744-14.723, P=0.001) , CD45 positive (HR=14.504, 95%CI 0.168-0.42, P=0.001) , LDH≥220 IU/L (HR=1.308, 95%CI 1.16-2.417, P=0.015) were independent risk prognostic factors.@*Conclusion@#CD45 expression is a risk prognostic factor of MM patients. Bortezomib did not improve the poor prognosis of CD45+ MM patients.

Correlation between myeloperoxidase expression and gene alterations and prognosis in acute myeloid leukemia / 中华血液学杂志

Objective@#To analyze the percentage of myeloperoxidase (MPO)-positive acute myeloid leukemia (AML) blast cells, and to explore the correlation of MPO expression with the clinical features, gene alterations, therapeutic response and prognosis of AML.@*Methods@#The expressions of MPO in BM blasts cells of 233 newly diagnosed AML were retrospectived analyzed, they were divided into two groups using the percentage of MPO-positive blast [low (≤70%) and high (>70%)], clinical features, gene alterations, chemotherapy efficacy and prognosis were compared between the two groups.@*Results@#①Of the 233 patients, 121(51.9%) were in the low MPO group, and the rest 112(48.1%) in the high MPO group. Favorable-risk group according NCCN guidelines of AML was always MPO-high (χ2=32.773, P<0.001), while MPO-low was closely related to poor-risk (χ2=7.078, P=0.008); ②DNMT3A mutation (χ2=6.905, P=0.009), spliceosome genes mutation (SF3B1/SRSF2/U2AF1) (χ2=5.246, P=0.022), RUNX1 mutation (χ2=4.577, P=0.032), ASXL1 mutation (χ2=7.951, P=0.005) and TP53 mutation (P=0.004) were more likely to be seen in the low MPO group, while C-KIT mutation (χ2=8.936, P=0.003) and CEBPA mutation (χ2=12.340, P<0.001) were more frequent in the high MPO group, especially CEBPA double mutation; ③The rates of first complete remission in the low MPO group were significantly lower than that in the high MPO group (38.8% vs 68.1%, χ2=15.197, P<0.001). Multivariate analysis showed that low MPO positivity significantly affected the CR1 unfavourably. ④The overall survival (OS) and the progression-free survival (PFS) were significantly worse in the low MPO group (18.0% vs 89.4% for OS, and 11.5% vs 56.7% for PFS, P<0.001). Multivariate analysis disclosed that the low number of MPO was significantly unfavourable prognostic factor. ⑤The low MPO group still showed a worse survival even when restricted to the patients with normal karyotype, the OS and the PFS were 31.1% and 18.8% respectively.@*Conclusions@#AML with different MPO expression percentage had a unique gene mutation spectrum. Low expression of MPO was an independent risk factor for CR1, OS and PFS in AML patients, which may be a simple and highly significant factor for AML patients when evaluating the therapeutic efficacy and prognosis.

Influence of single nucleotide polymorphism of Wilms tumor 1 gene on the efficacy and clinical prognosis of elderly patients with acute myeloid leukemia / 中华老年医学杂志

Objective To evaluate the influence of single nucleotide polymorphism of Wilms tumor 1(WT1)gene rs16754 on the chemosensitivity and clinical outcomes of elderly patients with acute myeloid leukemia(AML).Methods A total of 178 AML patients aged 60 years and over who received cytarabine-based chemotherapy were enrolled in this retrospective study.The peripheral blood was extracted from 178 AML patients receiving chemotherapy for DNA preparation and study.And bone marrow specimens were collected in 65 AML patients before chemotherapy.The Wilms' Tumor-1 (WT1) rs16754 polymorphism was detected by PCR-RFLP method.The association between genotypes and other variables were analyzed by using Logistic regression model.Variables were adjusted by Cox regression analysis.Results The locus of WT1 gene rs16754 is located in coding region of WT1 gene.The genotype frequency and distribution of the studied population were 55.62％ (99/178)in GG,37.64％(67/178)in GA,and 6.74％(12/178)in AA,with minimum allele frequencies of 0.26.The distributions of the three genotypes were in accordance with Hardy-Weinberg Equilibrium (P=0.884).There was no statistical difference in the data distribution of the genotypes on clinical indexes at baseline.Overall survival time(OS)was longer in patients with allele A and genotype GA plus AA[2.73 years(95 ％CI:1.03-5.11 years)]than in patients with GG genotype[1.64 years(95 ％ CI:0.71-4.34),(P=0.003)].The replase free survival(RFS) was longer in patients with allele A and genotype GA plus AA[2.06 years(95％CI:0.95-4.87)]than in patients with GG genotype[1.12 years(95％CI:0.56-4.11),P =0.032)].Adjusted by using multivariate Cox regression analysis,GA plus AA genotypes still showed a better effect on OS (HR =0.51,P =0.013)than did GG genotypes.In the 65 pretreatment bone marrow specimens,the expression level of WT1 mRNA in bone marrow cells was higher in patients with GG genotype than in patients with GA plus AA genotype(P ＜ 0.001).Conclusions Among elderly AML patients treated by cytarabine-based chemotherapy,the WT1 rs16754 may impact the clinical prognosis of AML patients by influencing the mRNA expression of WT1.

Progress in the mechanisms of multiple myeloma bone diseases / 白血病·淋巴瘤

Multiple myeloma bone diseases (MMBD) is a series of osteolytic changes caused by plasma cells malignant proliferation,including bone pain,hypercalcemia,osteoporosis,pathological fracture,etc.MMBD has insidious onset,high misdiagnosis rate and poor prognosis.The broken-up bone homeostasis model due to the activated osteoclasts and inhibited osteoblasts is considered as the core mechanism.More and more studies suggest that osteocyte is the key to regulate the activity of osteoclasts and osteoblasts,and the occurrence of MMBD is regulated by some cytokines.This article reviews the mechanisms of MMBD.

Analysis of clinical characteristics and prognostic factors in patients with non-Hodgkin lymphoma and HBV infection / 中华血液学杂志

Objective@#To explore the clinical characteristics and prognostic factors of the patients with non-Hodgkin’s Lymphoma (NHL) complicated with HBV infection, so as to provide a basis for clinical accurate diagnosis and prognosis evaluation.@*Methods@#The data of 313 newly diagnosed NHL patients from August 2012 to July 2016 were collected. The HBV serological markers were detected by ELISA, and HBV DNA was quantified by full automatic microparticle chemiluminescence immunoassay (≥1×105 copies/ml as high copy group, 1×103-<1×105 copies/ml as low copy group). The relationship between HBV infection and prognosis was analyzed combined with the clinical features of the patients, and the HBV detection rate was compared with that of the common population (from the national HBV sero epidemiological data).@*Results@#①The positive rate of HBsAg in NHL patients was 12.5% (39/313), which was higher than 7.2% in the general population (χ2=14.596, P<0.001). HBV infection in the past (HBsAg negative but HBcAb positive) in 114 cases (36.4%), the incidence was slightly higher than that in the general population (34.1%). ②Compared HBsAg positive group with the negative group, the proportion of B cell type (87.2% vs 70.3%, P=0.027), Ann Arbor stage Ⅲ-Ⅳ(69.2% vs 34.6%, P<0.001), IPI score 3-5 (74.4% vs 50%, P=0.004), LDH level (79.5% vs 47.8%, P<0.001) and liver involvement (45.5% vs 31.7%, P=0.006) were all higher. The difference was statistically significant. ③Compared the HBV infected group (114 cases) with the non-infected group (160 cases), the difference had statistical significance in the proportion of Ann Arbor stage Ⅲ-Ⅳ (P=0.023) and IPI score 3-5 scores P=0.035). ④Compared HBV DNA positive group (30 cases) with negative group (71 cases), Ann Arbor stage Ⅲ-Ⅳ (P=0.011), IPI score 3-5 score (P=0.030), LDH level (P=0.025) and liver involvement (P<0.001) in the proportion of patients had statistical significance. The positive patients were divided into HBV DNA high and low copy groups with 1×105 copies of /ml as the boundary. The results showed that there was no statistical difference between the two groups (P>0.05).@*Conclusions@#The HBV infection rate of NHL patients is significantly higher than that of the general population, and HBV infection is more closely related to B cell type NHL. Patients with HBV infection and HBV DNA positive had late Ann Arbor stage, high IPI score, high LDH level and liver involvement, and the prognosis is poor.

Comparison of different styles of allogeneic hematopoietic stem cell transplantation as first-line treatment treated with severe aplastic anemia in children and adolescents / 中华血液学杂志

Objective@#To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) .@*Methods@#The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT).@*Results@#The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS.@*Conclusion@#The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.

Efficacy observation of gemcitabine regimen and CHOP-like regimen as the first-line treatment of extranodal NK/T-cell lymphoma / 白血病·淋巴瘤

Objective To compare the efficacy and safety of combined regimen of gemcitabine and CHOP-like regimen as the first-line treatment for primary extranodal NK/T-cell lymphoma. Methods A retrospective analysis was carried out in 39 newly treated patients with extranodal NK/T-cell lymphoma in Henan Provincial People's Hospital from March 2012 to March 2017, in which 11 patients were treated with gemcitabine regimen and 28 patients were treated with CHOP-like regimen. The complete remission (CR) rate, partial remission (PR) rate, overall remission rate (ORR), overall survival (OS) rate, progression free survival (PFS) rate, and adverse reactions in the two groups were compared. Results In gemcitabine group and CHOP-like group, there were 5 and 8 cases achieved CR, 3 and 5 cases achieved PR. There was no statistically significant difference in CR rates and ORR between the two groups (P= 0.453, P= 0.073). The estimated 3-year OS rate in the two groups were 75 % and 33 %, and the estimated 3-year PFS rate were 70%and 29%, respectively. There was statistically significant differences in OS and PFS between the two groups (χ2 = 5.606, P= 0.018; χ2 = 3.924, P= 0.048). The univariate analysis showed that the treatment program (P=0.018) and the high lactate dehydrogenase (LDH) (P= 0.007) affected the prognosis of patients. Multivariate analysis showed that the high LDH increased the risk of death in patients (RR= 6.331, 95% CI 2.339-17.136, P< 0.001). Treatment with gemcitabine regimen reduced the risk of death in patients (RR=0.101, 95 %CI 0.023-0.452, P= 0.003). Most of the adverse events were 1-2 levels, and the patients were well tolerated. Conclusion Compared with CHOP-like regimen, the combined regimen of gemcitabine can improve the survival time of the patients with extranodal NK/T-cell lymphoma and significantly improve the long-term efficacy.

Allogeneic hematopoietic stem cell transplantation for intermediate cytogenetic risk acute myeloid leukemia / 中国组织工程研究

BACKGROUND: Previous studies have shown that HLA-identical sibling allogeneic peripheral blood hematopoietic stemcelltransplantation (allo-HSCT) provides higher disease-free and overall survival rates for patients with intermediatecytogenetic risk acute myeloid leukemia (AML) in complete remission (CR). But prognosis factors have not been fullydefined.OBJECTIVE: To evaluate the outcome of patients with intermediate cytogenetic risk AML undergoing HLA-matchedallo-HSCT in CR, and to analyze the prognostic factors.METHODS: Fifty cases of intermediate cytogenetic risk AML in CR receiving HLA-matched allo-HSCT from January2009 to January 2015 were retrospectively analyzed. Primary outcome measures of the study included overall survival(OS), relapse rate and non-relapse mortality.RESULTS AND CONCLUSION: The 4-year OS of the study population reached to 64%, and the relapse rate and NRMreached to 18% and 20% respectively. Incidence of acute graft-versus-host disease was 26%. Different prognosis wasobserved between female donor/male recipient (FDMR) combination transplant and control (4-year OS: 50% vs. 71.9%,P=0.041), between patients requiring more than one course of induction chemotherapy to achieve CR and control(4-year OS: 40% vs. 70%, P=0.038), between older age (≥ 40 years) and control (4-year OS: 44.4% vs. 68.3%,P=0.056). The 4-year OS for matched sibling donor and matched unrelated donor was 63.2% and 66.7% (P=0.427),respectively. Further analysis revealed significantly high non-relapse mortality in FDMR combination transplant (P=0.024)and older age (≥ 40 years; P=0.043). Multivariate analysis revealed three negative prognostic factors: FDMRcombination (P=0.031, RR=1.38, 95% CI: 1.03-1.95), requiring more than one course of induction chemotherapy toachieve CR (P=0.016, RR=1.46, 95% CI: 1.10-1.98) and older age (≥ 40 years; P=0.024, RR=1.63, 95% CI: 1.32-2.12).To conclude, HLA-matched allo-HSCT is a choice for the intermediate cytogenetic risk AML case in CR. FDMRcombination, requiring more than one course of induction chemotherapy to achieve CR and older age (≥ 40 years) areconfirmed as risk factors of poor prognosis for HLA-matched allo-HSCT patients with intermediate cytogenetic risk AMLin CR. To these cases, the donor-recipient sex combination is more important than the donor type in donor selection.

Efficacy of combination of ATRA, ATO and anthracyclines induction therapy in patients with acute promyelocytic leukemia / 中华血液学杂志

Objective@#To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL).@*Methods@#Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m-2·d-1, d1-28) + ATO (0.16 mg·kg-1·d-1, d1-28) + Idarubicin (8 mg·m-2·d-1, d3-5) /daunorubicin (40 mg·m-2·d-1, d3-5) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above. Of 184 cases, 69 cases accompanied with WBC counts>10×109/L, 115 cases with WBC counts≤10×109/L at onset.@*Results@#①Short-term efficacy: After one cycle induction therapy, the rates of hematologic remission, genetic remission, molecular remission and induced differentiation syndrome (DS) in three-drug regimen group were 98.3%, 87.9%, 72.4% and 0 respectively, while those in two-drug regimen group were 87.3%, 65.9%, 51.6% and 12.7% respectively. In patients with WBC >10×109/L, DS rate and early mortality in three-drug regimen group were lower than in two-drug regimen group (0 vs 15.6%, 4.2% vs 15.6%, respectively). In patients with WBC≤10×109/L, DS rate in three-drug regimen group was also lower than in two-drug regimen group (0 vs 12.3%) , but there were no statistical differences in terms of relapse and early mortality. ② Long-term efficacy: The relapse rate, overall survival (OS) and disease free survival (DFS) in three-drug regimen group were 0, 98.5%, 96.6% respectively, while those in two-drug regimen group were 8.6%, 86.5% and 84.1% respectively; the advantages of three-drug over two-drug regimen, especially in cases of WBC >10×109/L were observed. ③ Side effects: the incidences of gastrointestinal reaction, liver dysfunction, myocardial damage and headache in three-drug regimen group hardly increased.@*Conclusion@#The efficacies of three-drug induction therapy were superior to two-drug one.

The analysis of prognosis-associated factors in adults with acute promyelocytic leukemia / 中华血液学杂志

Objective@#To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) .@*Methods@#The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People’s Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored.@*Results@#①Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . ②At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ2=8.462, P=0.004; 16.1% vs 4.3%, χ2=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ2=5.610, P=0.018; 16.7% vs 4.4%, χ2=4.833, P=0.028, respectively) . ③The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34+, CD56+ or FLT3-ITD mutation were worse (P<0.05) .@*Conclusions@#Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.

miR-125b targets Sema4C regulating invasion and migration of Non-Hodgkin′s lymphoma by STAT3 signaling pathway involved / 中国免疫学杂志

Objective:To investigate the effect of miR-125b targeting Sema4C on STAT3 signaling pathway on invasion and metastasis of non-Hodgkin′s lymphoma.Methods: Expression of miR-125b in non-Hodgkin′s lymphoma tissues and cell lines was detected by QT-PCR.Expression of Sema4C in normal lymphocyte tissues and non-Hodgkin′s lymphoma tissues was detected by immunohistochemistry.Dual luciferase effect of miR-125b on the transcriptional activity of Sema4C was examined by the reporter gene system.Transwell invasion assay was used to detect the expression of miR-125b in the non-Hodgkin′s lymphoma cell line NK-92.Scratch test Western blot was used to detect the expression of Sema4C.Western blot was used to detect the protein expression of STAT3 signal pathway after silencing Sema4C.The protein expression of Sema4C was detected by Western blot.Results: Expression of miR-125b was significantly lower in non-Hodgkin′s lymphoma tissues than that in normal tissues[(0.48±0.05)% vs (1.59±0.38)%,P<0.05].Sema4C was highly expressed in non-Hodgkin′s lymphoma[(326.25±7.75)% vs (58.75±5.76)%].After overexpression of miR-125b,non-Hodgkin′s lymphoma cells expression level of Sema4C was down-regulated after silencing Sema4C[(326.25±7.75)% vs (58.75±5.76)%],and the expression of JAK and STAT3 protein were down-regulated after miR-125b overexpression[(85.26±6.94)% vs (12.61±4.32)%,P<0.05].The dual luciferase reporter gene system showed that miR-125b could directly regulate the transcriptional activity of Sema4C.Conclusion: miR-125b can regulate the invasion and migration of non-Hodgkin′s lymphoma cells by targets the expression of Sema4C.

Relationship between cytogenetics with therapy and prognosis in 124 patients with myelodysplastic syndrome / 白血病·淋巴瘤

Objective To explore the relationship between cytogenetics with therapy and prognosis in myelodysplastic syndrome.Methods 124 cases of myelodysplastic syndrome from September 2005 to October 2009 were reviewed.124 cases contained 79 males and 45 females,aged 14 to 79 years,median age was 57 years old.26 cases were diagnosed as RA,13 cases as RAS,21 cases as RCMD,29 cases as RAEB-Ⅰ,35 cases as RAEB-Ⅱ.According to the karyotype,124 cases were divided into two groups,79 cases of normal karyotype and 45 cases of abnormal karyotype.Patients were followed up for three years in order to analyze the incidence of myelodysplastic syndrome changed into acute leukemia.Results In 39 patients diagnosed as RA and RAS,32 cases were with normal karyotype and 7 cases (17.9 ％) with abnormal karyotype.15 of 32 cases with normal karyotype achieved hematologic remission after treatment while only 1 of 7 cases with abnormal karyotype achieved remission.1 case with abnormal karyotype changed into acute leukemia after 2 years.In 85 patients diagnosed as RCMD,RAEB-Ⅰ and RAEB-Ⅱ.Difference of the lower incidences of RA and RAS changed into acute leukaemia during 3 years in normal karyotype and abnormal karyotype groups was statistically insignificant (P ＜ 0.05).The incidences of RCMD,RAEB-Ⅰ and RAEB-Ⅱ changed into acute leukemia were higher,especially in the abnormal karyotype group with 42.1 ％.Conclusion Myelodysplastic syndromea with abnormal karyotype is associated with poorer efficacy of therapy,higher incidence of changing into acute leukaemia.The patients can take early allogeneic hematopoietic stem cell transplantation to improve the prognosis.

Comparison between clinical results of peripheral blood stem cell transplantation from HLA-matched sibling donors mobilized with different regimens / 中华器官移植杂志

Objective To retrospectively review and compare the clinical results of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA- matched sibling donors mobilized with different regimens. Methods Seventy-one patients with hematological malignant diseases received allo-PBSCT from HLA-matched sibling donors in our department. Among them, 24 received allografts mobilized with G-CSF (group G), and the remaining (47 cases) were mobilized with G-CSF and GM-CSF (group G+ M). CD34+ subsets and T cell subsets in the allografts were analyzed, and the time of hematopoietic reconstitution and the incidence of graft versus host diseases (GVHD) were compared. The adverse effects on the donors after mobilization were also observed. Results The enough targeted CD34+ cells in all donors were harvested by 1-3 aphereses. Ninety-six h after mobilization, WBC counts of the donors were significantly higher in group G than in group G + M [(49. 6± 19. 5) 109/L vs (25.4 ± 10. 4) 109/L, P＜0. 05]. Analysis of the CD34+ subsets showed that the percentage of cells with the CD34+/CD38- phenotype was significantly higher in group G + M than in group G [(37. 7 ± 5. 7) % vs (31.4 ± 4. 5) %, P＜0. 05]. There was no significant difference in T cells and subsets of grafts. There was no significant difference in the number of total CD34+ cells and CD34+ CD38- cells, and infusion of T cells between two groups. The days required for the recovery of neutrophils and platelets was inversely correlated with the infused CD34+ and CD34+ /CD38- cell number. There was no significant difference in incidence of acute and chronic GVHD between two recipient groups. Seventeen cases and 10 eases among 71 eases died of relapses of primarydiseases, and complications of transplantation such as severe GVHD and infections respectively.Fourteen cases in group G (58.3 %) and 31 cases in group G+ M (66.0 %) survived. The most common adverse events in the donors were bone pain and fever, which mostly occurred 36 h after mobilization and could be relieved by non-steroidal anti-inflammatory drugs. Conclusion Two mobilization regimens showed equivalent clinical results. But the combined regimen of G-CSF and GM-CSF demonstrated a significantly greater mobilization of cells with the CD34+/CD38- phenotype.Meanwhile in allogeneic PBSCT, a greater number of total CD34+ cells and CD34+ CD38- cells infused may be associated with faster hematopoietic reconstitution of recipients.

Treatment of relapsed acute leukemia by haplo-identical donor lymphocyte infusion / 白血病·淋巴瘤

Objective To evaluate the effect of haploidentical lymphocyte infusion on refractory and relapse acute leukemia. Methods The haploidentical donor lymphocyte infusion was used to treat for relapse acute myeloid leukemia 3 patients (M2 2 eases, M4 lcase), one relapse acute lymphocyte leukemia from April 2006 to October 2007. Four cases who had accepted secondly regimens were ineffective,after relapse. Collecting donor lymphocytes, parents children as donor supply in 3 cases, mother as donor supply one case. Before donor lymphocyte infusion patients received chemotherapy of different regimens. Donor haploidentical iymphocytes irradiated by 6-8 Gy radial were infused when patients white cell count was at the lowest after the chemotherapy. The average of infusion cells was 2.3 (1.4-3.1)×108/kg. Results One patient acquired complete remission and two patients were effective in three relapse acute myeloid leukemia. It was ineffective in relapse acute lymphocyte leukemia. No transfusion related graft versus host disease was observed. One patient has had herpes zoster virus infection. Conclusion Haploidentical donor lymphocyte infusion with chemotherapy are effective for refractory and relapse in acute myeloid leukemia, but the infused cell quantity and irradiated dosage must be further discussed.

Adenovirus infection associated with hemorrhagic cystitis after bone marrow transplantation / 白血病·淋巴瘤

To retrospect articles referred to the biological and infection features of adenovirus,analyzing the relationship between hemorrhagic cystitis after bone malTow transplantation with adenovirus infection and scrutinizing detective way and treatment in present.The accidence rate of hemorrhagic cystitis caused by adenovirug infection after bone marrow transplantation is higher in children than that in adults,in HLA non-matched than matched.and in GVHD accompanying than no GVHD.Conclusion:Adenovirus infection leading to hemorrhagic cystitis is a common complication after bone malTOw transplantation which indicates great value in early recognizing,early diagnosis,early treatment of adcnovirus infection in prevent hemorrhagic cystitis after bone marrow transplantation.