Myeloablative Haploidentical Transplant as an Alternative to Matched Sibling Transplant for Peripheral T-Cell Lymphomas.

The number of HLA-haploidentical allogeneic hematopoietic stem-cell transplantation (Haplo-HSCT) is increasing. Comparative studies about Haplo-HSCT versus allo-HSCT with HLA-matched sibling donors (MSD-HSCT) have been tried in leukemias and B-cell lymphomas. Few studies were reported in Peripheral T-cell lymphomas (PTCLs). We performed a multicenter retrospective study about 52 patients with PTCLs undergoing Haplo-HSCT (n = 20) or MSD-HSCT (n = 32). All Haplo-HSCT recipients received antithymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis. The median follow-up for all survivors was 38 months. The 100-day cumulative incidence of grade II to IV acute GVHD was similar (19% in the MSD-HSCT group versus 28% in the Haplo-HSCT group, P = 0.52). The 2-year cumulative incidence of chronic GVHD (limited and extensive) after Haplo-HSCT (30%) was also similar with that in the MSD-HSCT group (50%, P = 0.15). The 3-year relapse rates (33% vs 27%, P = 0.84) and non-relapse mortality (21% vs 22%, P = 0.78) did not differ between these two groups. There were also no differences in 3-year overall survival (OS) (48% vs 50%, P = 0.78) and progression-free survival (47% vs 51%, P = 0.95) between these two groups. On multivariate analysis, prognostic index for T-cell lymphoma (PIT) score (higher than 1: hazard ratio [HR], 4.0; P = 0.003) and disease status (stable or progression disease before HSCT: HR, 2.8; P = 0.03) were independent variables associated with worse OS. We concluded that ATG-based haplo-HSCT platform could work as an alternative to MSD-HSCT for patients with PTCLs.

Clinical characteristics of Covid-19 patients with re-positive test results: an observational study

BackgroundWith coronavirus disease 2019 (Covid-19) ravaging the global, concern has been aroused whether discharged Covid-19 patients with reappeared positive nucleic acid test results are infected again. ObjectiveTo analyze the clinical characteristics of discharged Covid-19 patients with reappeared positive nucleic acid test results and to track clinical outcomes of them. MethodsWe extracted clinical data on 938 Covid-19 patients from Wuhan Union Hospital (West Branch), and we obtained information about residual symptoms and nucleic acid tests after discharge through follow-up study. We evaluated the relationship of clinical characteristics and reappeared positive results. Each patient had at least 44 days of follow-up. ResultsOf 938 discharged patients, a total of 58 (6.2%) had reappeared positive nucleic acid test results and 880 remain negative. Among patients over the age of 50, the factors we found to be associated with re-positive results were coronary artery disease (14.1%, vs. 5.5% among those without coronary artery disease; odds ratio, 2.81; 95% confidence interval [CI], 1.28 to 6.15), and hypertension (9.5%, vs. 4.9% among those without hypertension; odds ratio, 2.05; 95% CI, 1.10 to 3.82). As of May 11, 2020, 54 (93.1%) re-positive patients turned negative again while two patients remained positive, and two patients was lost to the second follow-up. ConclusionCoexisting diseases including coronary artery disease and hypertension were substantial risk factors for re-positive outcomes among patients over 50. And most re-positive patients tended to return negative eventually.

Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) .@*Methods@#The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis.@*Results@#The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK+ and 9 ones (27.3%) ALK-. Of them, 25 patients (19 ALK+ and 6 ALK-) underwent auto-HSCT and 8 cases (5 ALK+ and 3ALK-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively.@*Conclusion@#ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma / 中华血液学杂志

Objective@#To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) .@*Methods@#From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively.@*Results@#Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) .@*Conclusion@#Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning.

Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy). A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched. We were particularly interested in whether the dosage of Cy significantly impacted graft failure (GF) and overall survival (OS). All patients showed sustained hematopoietic engraftment without any increase in severe aGVHD and transplantation-related mortality (TRM). The incidences of grade II-IV aGVHD, grade III-IV aGVHD and extensive cGVHD were 18%, 10% and 7%, respectively. The probabilities of 1-year and 5-year OS were 93.1% and 87.9%, respectively. Furthermore, patient age <15 years, MNC cells >8×108/kg and donor age <45 years were associated with better survival (P=0.043, P=0.023, and P=0.037, respectively) and engraftment (P=0.019, P=0.008, and P=0.001, respectively). Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen. Improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.

Clinical study on foscarnet prophylaxis and pre-emptive therapy for cytomegalovirus infection in hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective To observe the clinical safety and efficacy of foscarnet prophylaxis and pre-emptive therapy for cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Ninety-six patients undergoing allo-HSCT from October 2014 to December 2016 were retrospectively analyzed. Plasma CMV-DNA was monitored with real-time quantitative polymerase chain reaction (RQ-PCR) from beginning to 180 days after transplantation. Foscarnet was used not only for prophylaxis but also for first-line pre-emptive therapy when plasma CMV-DNA turned to positive. Foscarnet was given 60 mg·kg-1·d-1 and 120 mg·kg-1·d-1 respectively in prevention and pre-emptive therapy. Incidences of CMV infection and CMV disease were observed, influencing factors on CMV in faction and the efficacy and safety of foscarnet prophylaxis were analyzed, and survival of patients treated by all-HSCT was evaluated. Results Of the total 96 patients, 42 cases (43.8%) had CMV infection with the median time of 42 days after allo-HSCT. CMV-DNA became negative in 36 patients (85.7%, 36/42) after pre-emptive therapy. Six patients (14.3 %, 6/42) developed CMV disease, including 5 patients with CMV negative and 1 patient died for CMV pneumonia. Haploidentical donor and grade Ⅱ-Ⅳacute graft versus host disease (GVHD) were the risk factors for CMV reactivation (χ2 = 3.834, P< 0.05; χ2 = 16.807, P< 0.001). The side effects of foscarnet prophylaxis were mild without hematologic toxicities. 12 patients (28.6 %) died in 42 patients with CMV infection, and 6 patients (11.1 %) died in 54 patients without CMV infection. The difference of survival rates between both groups was not statistically significant. Conclusion Foscarnet is an effective agent for prophylaxis and pre-emptive therapy in CMV infection after allo-HSCT with mild adverse reactions, especially for patients following with hematopoietic recovering.

Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia / 中华血液学杂志

Objective@#To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) .@*Methods@#Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis.@*Results@#Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (HR=2.656, 95%CI 1.204-5.858, P= 0.016) and the level of serum ferritin before tansplantation (HR=3.170, 95%CI 1.400-7.180, P=0.006) were significant risk factors for PGF.@*Conclusion@#Unrelated donor transplantation and the high level of serum ferritin before transplantation are risk factors for PGF.

Effect of amifostine on proliferation and differentiation of human megakaryocyte Dami cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P1.0 mmol·L-1).

CXCR4 expression of bone marrow CD34+cells in myelodysplastic syndromes and its correlation with cell migration / 中国肿瘤临床

Objective:To evaluate the expression of CXCR4 and the migration rate of bone marrow stromal CD34+cells in differ-ent risk groups with myelodysplastic syndromes (MDS) using correlation analysis. Methods: Forty MDS patients were divided into low-and high-risk groups based on the International Prognosis Scoring System (IPSS). The former was composed of 20 patients with IPSS0.05). The migration rate of CD34+cells on the ef-fects of SDF-1αand marrow stromal cells were significantly increased in the high-risk MDS group compared with those in the low-risk and control groups (P<0.000 1). Migration rate of CD34+cells on the effect of marrow stromal cells was positively correlated with CX-CR4 expression (P=0.000 1). Conclusion:The CXCR4 expression and migration rates of CD34+cells on the effect of marrow stromal cells are significantly higher in the high-risk MDS group than in the low-risk group. Migration rate has a positive correlation with the CXCR4 expression, which further indicates that MDS is a heterogeneous group of hematopoietic stem cell malignancies. The expres-sion and function of SDF-1 and its receptor CXCR4 differ within each group with various risks. SDF-1 and CXCR4 may be involved in MDS pathogenesis.

Effect of Conjugated Linoleic Acid (CLA) on Lipid Metabolism and Expression of Visfatin Gene in Rats with Hyperlipidemia / 中国实验动物学报

Objective To establish a rat model of hyperlipidemia and analyze the effect of conjugated linoleic acid (CLA) on lipid metabolism and expression of visfatin gene. Method High fat diet was used to establish the hyperlipidemia rat model. Blood was taken at four weeks after high fat diet feeding to analyze the level of glucose (GLU), cholesterol (CHO) and triglyeride(TG). The rats were divided into experimental group and control group after the hyperlipidemia rat model was established successfully. The experimental group rats were treated with CLA(0.8 mL /0.1 kg)orally for four weeks. The food intake and body weight were recorded. The rats were sacrificed, and both body fat and serum lipid levels were measured. Semi-quantitative RT-PCR was used to measure the expression level of visfatin mRNA. Result The hyperlipidemic rat models were induced by high fat diet successfully. The body weight, food intake and body fat in the rats of CLA experiment group were significantly decreased compared with that of the control group (P< 0.05). The level of GLU, CHO, TG and LDL in the experimental group were significantly lower than that in the control group (P< 0.05), but the serum HDL-C was increased in the experimental group. Semi-quantitative RT-PCR demonstrated that the expression level of visfatin gene of the experimental group was lower than that in the control group. Conclusion CLA can reduce the expression of visfatin gene and improve the lipid metabolism in hyperlipidemic rats.

Analysis of TCM treatment mode / 中华中医药杂志

Chinese herbal medicine has the double attribute of treatment aiming at symptom and syndrome. The use of formula according to symptoms is the basis of determination of treatment based on differentiation of indications and formula, and the use of formula according to TCM syndrome type is the basis of determination of treatment based on differentiation of symptoms and signs. The determination of treatment based on differentiation of formula and sign is a therapy deriving from experience, but determination of treatment based on differentiation on syndrome and signs a method from theoretical medical science. Both of them are difficult to master. Therefore, it suggests that do not try to master the other unless one of them has being mastered.

IDENTIFICATION OF LEPTIN GENE FROM HUMAN PLACENTA AND ITS FUSION EXPRESSION IN ESCHERICHIA COLI / 解剖学报

Objective To identify the sequence of cDNA of human leptin coding region, construct a prokaryotic expression vector, and express human leptin in E.coli. Methods RNA was extracted from human placenta tissue. Leptin gene was amplified from RNA by RT-PCR method. The PCR product was ligated with T vector. The ligation reaction was transformed to E.coli DH5? competent cells. The recombinant plasmid was checked by sequencing and restriction analysis. The human leptin gene was cloned into prokaryotic expression vector PET-28a and tranformed into E.coli BL21. The recombinant strain was constructed and induced by IPTG. The product was analyzed with SDS-PAGE and Western blotting. The expressive product was purified by sodium deoxycholate. Results Analysis indicated that the sequence of human leptin cDNA was the same with the reported sequence. Leptin gene was inserted into prokaryotic expression vector. The fusion protein expressed with high efficiency in recombinant E.coli BL21.The results of SDS-PAGE analysis indicated that the molecular weight of the fusion protein was about 20kD. Conclusion Hunam leptin gene was successfully identified from placenta. The leptin gene prokaryotic expression strain was constructed and a high expression of leptin was achieved in E.coli.

Clinical analysis of 35 cases of malignant lymphoma with original appearance of abdominal masses / 中国实用内科杂志

Objective To find out the clinical characteristics of the group of lymphoma patients with original appearance of abdominal mass through analysis of their clinical manifestation,pathology and treatment outcome.Methods Retrospective study of clinical data of 35 cases,who were admitted to PLA General Hospital from 1998 to 2003,was made as to their age,sex,pathological pattern,size of the mass at diagnosis,and accompanying symptoms,blood examination,therapy and effect with follow-up of 16~96 months.Results Seventy-four point 3 percent of the patients were male,and most of them(71.4%)with enlarged post peritoneal lymphatic nodes.Ninety-one point four percent of the patients were non-Hodgkin lymphoma and nearly half of them aged between 40 to 50.NHL patients(65.6%)of B-cell origin were more than those of T-cell origin(28.1%).One out of three HL patients died of disease relapse.Nine NHL patients died,including 6 who received conventional chemotherapy and 3 who underwent stem cell transplantation.Half of the patients(2/4)who had hepatic dysfunction and acites died.Conclusion Lymphoma patients with original appearance of abdominal mass are mostly seen in male,and most are of B cell origin.Huge mass,acites and hepatic dysfunction indicate unfavourable prognosis.LDH and ?_2-MG may be two of the prognostic factors.

THE EFFECT OF ATRA-INDUCED DIFFERENTIATION OF LEUKEMIA CELLS ON WT1 EXPRESSION IN LEUKEMIA / 解放军医学杂志

To elucidate the relationship between WT1 expression and differentiation of leukemia cells and the role of WT1 gene in differentiation of leukemia cells, HL 60 and K562 cell lines were induced for 5 days by all trans retinoic acid(ATRA).Then the degree of differentiation and WT1 expression of cell lines were determined by NBT reduction assay and RT PCR respectively. The resultsshowed that only differentiation of HL 60 cells but no K562 cells could be induced by ATRA. When HL 60 cells were induced to differentiate to granulocytes by ATRA, the expression of WT1 decreased markedly during differentiation. However, WT1 transcripts were not significantly altered in K562 cells in which differentiation wasn't found. It suggested that WT1 gene expression may relate to the differentiation of leukemia cells.