Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 187
Filter
1.
Chinese Journal of Hematology ; (12): 400-407, 2022.
Article in Chinese | WPRIM | ID: wpr-929627

ABSTRACT

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.


Subject(s)
Antibodies, Monoclonal/pharmacology , Graft vs Host Disease/metabolism , Hematopoietic Stem Cell Transplantation , Humans , Killer Cells, Natural , Retrospective Studies , Treatment Outcome
2.
Chinese Journal of Hematology ; (12): 221-228, 2022.
Article in Chinese | WPRIM | ID: wpr-929561

ABSTRACT

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .


Subject(s)
B-Lymphocytes , Graft vs Host Disease , HLA Antigens/genetics , Haplotypes , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Retrospective Studies , Siblings
3.
Chinese Journal of Hematology ; (12): 134-140, 2022.
Article in Chinese | WPRIM | ID: wpr-929545

ABSTRACT

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.


Subject(s)
Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Retrospective Studies , Sulfonamides
4.
Chinese Journal of Hematology ; (12): 54-62, 2022.
Article in Chinese | WPRIM | ID: wpr-929530

ABSTRACT

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.


Subject(s)
Adult , Antineoplastic Agents/therapeutic use , Dasatinib/therapeutic use , Demography , Humans , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Treatment Outcome
5.
Chinese Medical Journal ; (24): 1199-1208, 2021.
Article in English | WPRIM | ID: wpr-878101

ABSTRACT

BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.


Subject(s)
B-Lymphocytes , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Recurrence , Retrospective Studies , Risk Factors , Stem Cell Transplantation
6.
Article in Chinese | WPRIM | ID: wpr-888052

ABSTRACT

The chemical constituents from the leaves of Ilex guayusa were investigated. Sixteen triterpenoids were isolated from the 95% ethanol extract of dried leaves of I. guayusa by silica gel, Sephadex LH-20, and ODS column chromatographies and semi-prepa-rative HPLC. Those triterpenoids were identified by NMR, HR-MS, and literature analysis: 3β-hydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13β-olide(1), 3β-hydroxy-24-nor-4(23),12-oleanadien-28-methyl ester(2), oleanolic acid(3), 3β,28-dihydroxy-12-oleanene(4), 2α,3β-dihydroxy-11α,12α-epoxy-24-'nor-olean-4(23)-ene-28,13β-olide(5), ursolic acid(6), 3β,23-dihydroxy ursolic acid(7), 3β,28-dihydroxy-12-ursene(8), 3β-28-nor-urs-12-ene-3,17-diol(9), 3β-hydroxyurs-11-ene-28,13β-olide(10), 13β,28-epoxy-3β-hydroxy-11-ursene(11), 3β-hydroxy-28,28-dimethoxy-12-ursene(12), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid(13), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-methyl ester(14), 2α,3β-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23)-ene-28,13β-olide(15) and 2α,3β-dihydroxy-11α,12α-epoxy-24-nor-urs-4(23),20(30)-dien-28,13β-olide(16). Compounds 1-2 were new compounds, and compounds 4-5, 7 and 9-16 were isolated from I. guayusa for the first time.


Subject(s)
Drugs, Chinese Herbal , Ilex guayusa , Molecular Structure , Oleanolic Acid , Plant Leaves , Triterpenes
7.
Article in Chinese | WPRIM | ID: wpr-887986

ABSTRACT

Mansoa alliacea,commonly known as garlic vine,is native to the tropical rain forests of South America and widely cultivated in South China. As a popular folk medicine with various biological activities,however,this plant remains to be fully elucidated in terms of its phytochemical constituents. In this study,two new pyranonaphthoquinones were isolated from the 95% ethanol extract of the leaves and twigs of M. alliacea by various chromatographic approaches including silica gel,octadecyl silica( ODS),Sephadex LH-20,and preparative high-performance liquid chromatography( PHPLC). Their structures were determined to be 8,9-dimethoxy-α-lapachone( 1) and 7-hydroxy-8,9-dimethoxy-α-lapachone( 2) by comprehensive spectroscopic analyses and therefore respectively named as mansonin A( 1) and mansonin B( 2).


Subject(s)
China , Chromatography, High Pressure Liquid , Phytochemicals , Plant Leaves
8.
Article in English | WPRIM | ID: wpr-827231

ABSTRACT

Three new indole alkaloids, flueindolines A-C (1-3), along with nine known alkaloids (4-12), were isolated from the fruits of Flueggea virosa (Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro (pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1-3 were herein also proposed.

9.
Chinese Medical Journal ; (24): 1765-1772, 2019.
Article in English | WPRIM | ID: wpr-771162

ABSTRACT

BACKGROUND@#Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs).@*METHODS@#Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up.@*RESULTS@#Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD.@*CONCLUSION@#Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

10.
Article in Chinese | WPRIM | ID: wpr-774345

ABSTRACT

OBJECTIVE@#To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes (MDS).@*METHODS@#The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitor-related cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation (CV) and CD71CV. According to our previous study, the percentage of CD117CD105 myeloid progenitor cells and the proportion of CD105 cells in CD117 cells were selected to establish a two-parameter scoring system, and compared with the four-parameter scoring system and the erythroid scoring system.@*RESULTS@#The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%.@*CONCLUSION@#Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.


Subject(s)
Endoglin , Flow Cytometry , Humans , Immunophenotyping , Myelodysplastic Syndromes , Diagnosis , Proto-Oncogene Proteins c-kit , Retrospective Studies
11.
Chinese Medical Journal ; (24): 1765-1772, 2019.
Article in English | WPRIM | ID: wpr-802695

ABSTRACT

Background@#Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs).@*Methods@#Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up.@*Results@#Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ2 = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ2 = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD.@*Conclusion@#Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

12.
Article in Chinese | WPRIM | ID: wpr-941828

ABSTRACT

OBJECTIVE@#X-linked adrenoleukodystrophy (ALD) is a severe inherited disorder leading to rapid neurological deterioration and premature death. Allogeneic hematopoietic stem cell transplantation (HSCT) is still the only treatment that halts the neurologic symptoms in ALD. However, many patients lack suitable human leukocyte antigen (HLA) matched related donors and must rely on alternative donors for a source of stem cells. The purpose of this study was to explore the outcomes of haploidentical allogeneic stem cell transplantation for ALD patients.@*METHODS@#Between December 2014 and December 2018, eight children with ALD lacking HLA matched related or unrelated donors were treated with haploidentical allogeneic hematopoietic stem cell transplantation. The patients received conditioning regimen with busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg and fludarabine 90 mg/m2. Graft-versus-host disease (GVHD) prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate.@*RESULTS@#All the 8 children received allogeneic stem cell transplants from their fathers. The median age of the recipients was 8 (range: 5-12) years. The median age of the donors was 36 (range: 32-40) years. All the recipients received granulocyte colony-stimulating factor (G-CSF) mobilized bone marrow and peripheral blood-derived stem cells. The median number of total mononuclear cells dose and CD34+ dose was 10.89 (range: 9.40-12.16)×108/kg and 7.06 (range: 0.74-7.80)×106/kg, respectively. Neutrophil engraftment occurred a median of 11 days (range:8-13 days) after transplantation. Platelet engraftment occurred a median of 10 days (range:8-12 days) after transplantation. All the patients achieved complete donor chimerism at the time of engraftment. Four patients had grades II-IV acute GVHD and 1 had chronic graft-versus-host disease. No severe chronic GVHD occurred. Among all the children, 2 had cytomegalovirus (CMV) DNAemia and 2 Epstein-Barr virus (EBV) DNAemia. Overall, seven of them survived and had no major complications related to transplantation. One died of cerebral hernia after epilepsy 125 days after transplantation.@*CONCLUSION@#The preliminary observation demonstrates that haploidentical allogeneic stem cell transplantation with this novel regimen could successfully achieve full donor chimerism in ALD patients. According to our experience, haploidentical allogeneic hematopoietic stem cell transplantation is safe and feasible in the treatment of X-linked adrenoleukodystrophy.


Subject(s)
Adrenoleukodystrophy/therapy , Adult , Bone Marrow Transplantation , Child , Child, Preschool , Chromosomes, Human, X , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Transplantation Conditioning
13.
Chinese Medical Journal ; (24): 2808-2816, 2018.
Article in English | WPRIM | ID: wpr-772917

ABSTRACT

Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Pathology , Therapeutics , Male , Middle Aged , Neoplasm, Residual , Diagnosis , Prognosis , Retrospective Studies , Transplantation, Homologous , Young Adult
14.
Article in Chinese | WPRIM | ID: wpr-775318

ABSTRACT

This study aims to establish the characteristic fingerprint of the leaves of Moringa oleifera by Ultra High Performance Liquid Chromatography (UPLC) for its quality control. The method was developed on a column of Agilent Eclipse XDB-C₁₈ with acetonitrile-0.01% TFA solution as the mobile phase by gradient elution at a flow rate of 0.5 mL·min⁻¹. The detective wavelength was 210 nm, and the column temperature was 35 °C. The 14 batches of the leaves of M. oleifera were compared for the similarity by using Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System (2004A). The UPLC characteristic fingerprint was established, and twelve common peaks were identified by comparison with the references and UPLC-MS. The relative retention times were 0.08 (No. 1, adenosine), 0.14 (No. 2, L-phenylalanine), 0.22 (No. 3, 5-caffeoylquinic acid), 0.28 (No. 4, L-tryptophane), 0.42 (No. 5, 4-caffeoylquinic acid), 0.65 (No. 6, vicenin-2), 0.94 (No. 7, vitexin), 0.96 (No. 8, isovitexin), 1.00 (No. 9, isoquercitrin), 1.11 [No. 10, quercetin 3-O-β-D-(6"-malonyl)-glucopyranoside], 1.21 (No. 11, astragalin) and 1.37 [No. 12, kaempferol 3-O-β-D-(6"-malonyl)-glucopyranoside]. It is the first time to establish the UPLC characteristic fingerprint of the leaves of M. oleifera. The method is simple, quick and reproducible with high precision, which can provide a scientific basis for the quality control of the leaves of M. oleifera.


Subject(s)
Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Moringa oleifera , Quality Control , Tandem Mass Spectrometry
15.
Chinese Journal of Zoonoses ; (12): 73-78, 2018.
Article in Chinese | WPRIM | ID: wpr-703070

ABSTRACT

To study the immune protection of the inactivated vaccine against the enteropathogenic E.coli in Tibetan pigs,the strains isolated from the dead pig was identified by biochemistry and PCR methods.After that,the biological adjuvant vaccine was prepared by following procession.Firstly,selected enteropathogenic E.coli strain was cultured.Then,we harvested the bacteria and inactived it to prepare the antigen.Finally,we added the recombined cholera toxin B subunit as the biological adjuvant,added the mannose in solution 3 %-5% (W/V),distributed in ampoule,and freeze-dried.The performances of the vaccine was evaluated by administration for the nine groups of KM mice in oral and intramuscular immuno strategies,respectively.Results demonstrated that the effect of intramuscular injection of low dose containing adjuvant group were better than those without adjuvant group.The oral group contained both high dose of adjuvant group and low dose effect of immune adjuvant group were better than that of high and low dose not containing adjuvant group,and high dose of immune effect was better than low dose immune effect.The antibody titers proved that immunization for 4 times was much better than those immunization for times less than that.The data showed the vaccine was high protection against Tibetan Pig enteropathogenic E.coli challenge,especially the high dose of adjuvant vaccine was 100% protection rate against enteropathogenic E.coli when orally immunization for 4 times in mice.

16.
Article in Chinese | WPRIM | ID: wpr-690526

ABSTRACT

Nineteen compounds were isolated from the roots of Isatis indigotica through silica gel, Sephadex LH-20, ODS and pre-HPLC chromatography technique. Their structures were elucidated by the MS and NMR spectra as 7-hydroxydeoxyvasicinone (1), (1H-indol-3-yl) oxoacetamide (2), 1-methoxy-1H-indole-3-acetonitrile (3), arvelexin (4), 1H-indole-3-acetonitrile (5), 1H-indole-3-aldehyde (6), 1H-indole-3-acetic acid (7), 2,3-dihydro-4-hydroxy-2-oxo-indole-3-acetonitrile (8), deoxyvasicinone (9), indigotiisocoumarin A (10), cycloanthranilylproline (11), quinazoline-2,4(1H,3H)-diones (12), indirubin(13), (+)-pinoresinol (14), (+)-epipinoresinol (15), burselignan (16), (+)-isolariciresinol (17),vanillic acid (18) and 5-hydroxymaltol (19). Among them, compound 1 is a new natural product, and compound 2, 14, 15, 18 and 19 were isolated from the title plant for the first time.

17.
Article in Chinese | WPRIM | ID: wpr-690403

ABSTRACT

Two new flavonoid glycosides, quercetin-3--(4--crotonyl)--D-glucopyranoside (1) and quercetin-3--[6--(2)-pentenoyl]--D-glucopyranoside (2), along with nine known ones, isoquercetin (3), astragalin (4), quercetin-3--(6--acetyl)--D-glucopyranoside (5), kaempferol-3--(6--acetyl)--D-glucopyranoside (6), quercetin-3--(6--crotonyl)--D-glucopyranoside (7), kaempferol-3--(6--crotonyl)--D-glucopyranoside (8), vitexin (9), isovitexin (10), and isorhamnetin-3---D-glucopyranoside (11), were isolated from the leaves of Moringa oleifera by various chromatographic technologies. Their structures were elucidated by spectroscopic methods including UV, IR, MS, and NMR. In addition, compounds 7 and 8 were isolated from this plant for the first time.

18.
Chinese Medical Journal ; (24): 2185-2192, 2018.
Article in English | WPRIM | ID: wpr-690246

ABSTRACT

<p><b>Background</b>The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA).</p><p><b>Methods</b>A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis.</p><p><b>Results</b>A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14 (P = 0.018) and CD34 cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed.</p><p><b>Conclusions</b>These results provide evidence and explain that higher doses of CD34 and CD14 cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.</p>


Subject(s)
Adolescent , Adult , Allografts , Anemia, Aplastic , Therapeutics , Child , Child, Preschool , Female , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Retrospective Studies , Transplantation Conditioning , Transplantation, Haploidentical , Transplantation, Homologous , Young Adult
19.
National Journal of Andrology ; (12): 442-446, 2018.
Article in Chinese | WPRIM | ID: wpr-689736

ABSTRACT

The MAPK signaling pathway plays a key role in the differentiation, proliferation and apoptosis of cells, and its family members mainly include extracellular signal-regulated kinase (ERK), stress-activated protein kinase (JNK), and p38 mitogen-activated protein kinase (p38MAPK). Recent studies have shown that the ERK, JNK and p38MAPK signaling pathways are closely associated with the development and progression of erectile dysfunction (ED). This review focuses on the correlation between the MAPK signaling pathway and ED.


Subject(s)
Apoptosis , Cell Differentiation , Cell Proliferation , Erectile Dysfunction , Metabolism , Humans , JNK Mitogen-Activated Protein Kinases , Metabolism , MAP Kinase Signaling System , Male , Mitogen-Activated Protein Kinases , Metabolism , Signal Transduction , p38 Mitogen-Activated Protein Kinases , Metabolism
20.
Article in Chinese | WPRIM | ID: wpr-258487

ABSTRACT

A new δ-oleanane-type triterpenoid glycoside, 3-O-(3-O-sulfo)-β-D-glucopyranosiduronic acid 3β-hydroxy-13(18)-oleanen- 28-oic acid 28-β-D-glucopyranosyl ester (1), along with ten known triterpenoid glycosides, rotundinoside A (2), oblonganoside M (3), 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl 3β,19α-dihydroxy-20α- urs-12-en-28-oic acid 28-O-β-D- glucopyranosyl ester (4), ilexsaponin B2 (5), ilexside Ⅱ (6), rotundinoside B (7), ilekudinoside B (8), ilexpublesnin E (9), ilekudinoside D (10) and ilexpernoside D (11), was isolated from the 75% ethanol extract of the roots of Ilex asprella by various chromatographic separation. Their structures were identified on the basis of MS, NMR spectroscopic analysis and chemical methods. In addition, 2-11 were isolated from I. asprella for the first time.

SELECTION OF CITATIONS
SEARCH DETAIL