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1.
Journal of Experimental Hematology ; (6): 1123-1126, 2020.
Article in Chinese | WPRIM | ID: wpr-827152

ABSTRACT

OBJECTIVE@#To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML).@*METHODS@#The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis.@*RESULTS@#Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival,and no patient relapsed.@*CONCLUSION@#UCBT is an effective treatment for children with JMML.


Subject(s)
Child , Child, Preschool , Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Infant , Leukemia, Myelomonocytic, Juvenile , Male , Retrospective Studies , Transplantation Conditioning
2.
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.

3.
Journal of Experimental Hematology ; (6): 1246-1252, 2019.
Article in Chinese | WPRIM | ID: wpr-775733

ABSTRACT

OBJECTIVE@#To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).@*METHODS@#Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen,and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.@*RESULTS@#The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)>0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival.@*CONCLUSION@#UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.


Subject(s)
Cord Blood Stem Cell Transplantation , Core Binding Factor Alpha 2 Subunit , Graft vs Host Disease , Humans , Leukemia, Myeloid, Acute , Mycophenolic Acid , Oncogene Proteins, Fusion , Peripheral Blood Stem Cell Transplantation , RUNX1 Translocation Partner 1 Protein , Transplantation Conditioning
4.
Journal of Experimental Hematology ; (6): 1633-1640, 2019.
Article in Chinese | WPRIM | ID: wpr-775672

ABSTRACT

OBJECTIVE@#To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT).@*METHODS@#Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation.@*RESULTS@#The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×10 /L vs 0.25×10 /L, P=0.015 and 2.53×10 /L vs 1.36×10 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8 T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×10 /L vs 0.10×10 /L, P=0.038 and 1.62×10 /L vs 0.68×10 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively.@*CONCLUSION@#The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8 T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.


Subject(s)
CD8-Positive T-Lymphocytes , Cord Blood Stem Cell Transplantation , Cytomegalovirus , DNA , Hematopoietic Stem Cell Transplantation , Humans , Immune Reconstitution
5.
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.

6.
Chinese Medical Journal ; (24): 1767-1775, 2018.
Article in English | WPRIM | ID: wpr-775145

ABSTRACT

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.


Subject(s)
Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , China , Cyclophosphamide , Doxorubicin , Female , Follow-Up Studies , Humans , Lymphoma, Follicular , Drug Therapy , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Male , Middle Aged , Prospective Studies , Rituximab , Therapeutic Uses , Vincristine
7.
Article in Chinese | WPRIM | ID: wpr-259591

ABSTRACT

<p><b>OBJECTIVE</b>This study was aimed to detect the FLT3 gene mutation in patients with de-novo acute myeloid leukemia (AML), and to investigate its prognostic value and clinical significance.</p><p><b>METHODS</b>Polymerase chain reaction (PCR) was used to detect FLT3 gene mutation, in bone marrow samples of 54 patients with de novo AML.</p><p><b>RESULTS</b>The incidence of FLT3-ITD mutation in 54 de-novo AML patients was 22.22%, 10 out of 12(83.3%) AML patients were identified with normal karyotype, while 16.7% patients were identified as with abnormal karyotype. The peripheral blood white cell count and bone marrow blast cells were significantly higher in the patients with FLT3-ITD mutation than those in patients without FLT3-ITD mutation (P<0.05), but there was no statistically significant difference in sex, age, CR rate of the first course induction chemotherapy, survival rate and so on between the two groups. Two cases had FLT3-TKD gene mutation; as compared with FLT3-TKD negative AML patients there was no statistical difference in sex, age, white blood cell count, the percentage of marrow blasts and CR rate of the first course of treatment at the initial diagnosis.</p><p><b>CONCLUSION</b>FLT3-ITD mutation positive likely occurs in AML patients with normal karyotype, the FLT3-ITD mutation is associated with higher peripheral white cell count and higher percentage of bone marrow blast cells.</p>


Subject(s)
Abnormal Karyotype , Hematopoietic Stem Cells , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute , Leukocyte Count , Mutation , Polymerase Chain Reaction , Prognosis , fms-Like Tyrosine Kinase 3
8.
Article in Chinese | WPRIM | ID: wpr-349693

ABSTRACT

This study was purposed to comparatively analyze the early T-lymphocyte subsets and T-cell receptor excision cycles (TREC) reconstruction in recipients with hematologic malignancies after myeloablative unrelated cord blood transplantation (UCBT) and sibling donor bone marrow and/or peripheral blood stem cell transplantation (BMT/PBSCT). The peripheral blood T lymphocyte subsets were detected using flow cytometry and TREC were detected using real-time quantitative PCR for 40 patients with hematologic malignancies in the first six months after myeloablative allogenic hematopoietic stem cell transplantation. The results showed that in the first month after transplantation, the absolute counts of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+) cells were lower significantly in the UCBT group than those in the BMT/PBSCT group. And later the absolute counts of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) cells were not different between two groups. The ratio of CD3(+)T subset in the peripheral blood lymphocytes of the UCBT recipients was lower, but the difference was not statistically significant within 2 months after transplantation. The ratio of CD3(+)CD4(+) cells in the patients received the UCBT and BMT/PBSCT decreased obviously since engraftment happened. The CD3(+)CD4(+) cells on the 2 months after transplantation fell to the lowest level, then gradually increased, but did not reach to the normal level until 6 months after transplantation. CD3(+)CD8(+)cells were well reconstituted, rising to normal at the engraftment after transplantation, with a low CD4(+): [KG-*2] CD8(+) ratio over the first 6 months after transplantation. Compared with the BMT/ PBSCT group, the naive T cells (CD3(+)CD4(+)CD45RA(+)CD62L(+)) were more in the first month after transplantation and the terminally differentiated effector memory T cells (CD3(+)CD4(+)CD45RA(+)CD62L(-)) were more at the 3 month after transplantation in the UCBT group, and those were significantly more than the normal control group. TREC were lower and did not recovered until 6 months after transplantation in the recipients of the two groups. It is concluded that compared with sibling donor's BMT/PBSCT, early T cell reconstitution significantly delayed after UCBT, but the terminally differentiated effector memory T cells are higher after transplantation, and thus play a anti-infective or anti-leukemia role.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Fetal Blood , Transplantation , Hematopoietic Stem Cell Transplantation , Methods , Humans , Male , Receptors, Antigen, T-Cell , Allergy and Immunology , T-Lymphocyte Subsets , Allergy and Immunology , Young Adult
9.
Journal of Experimental Hematology ; (6): 1415-1421, 2014.
Article in Chinese | WPRIM | ID: wpr-340487

ABSTRACT

This study was aimed to investigate the effect of high mobility group box1(HMGB1) and/or stromal cell derived factor-1(SDF-1) on the migration of cord blood CD34⁺ cells, and to explore whether HMGB1 promotes cord blood CD34⁺ cell migration via SDF-1/CXCR4 axis. Cord blood mononuclear cells were isolated by Ficoll-Paque density centrifugation, CD34⁺ cells were collected by a positive immunoselection procedure (CD34 MicroBeads) according to the manufacturer's instructions, the purity of the isolated CD34⁺ cells was detected by flow cytometry. In vitro chemotaxis assays were performed using Transwell cell chambers to detect cells migration. 1 × 10⁵ cells/well cord blood CD34⁺ cells were added into the upper chambers. Different concentrations of HMGB1 and/or SDF-1 (0, 10, 25, 50, 100, 200 ng/ml) were used to detect the optimal concentrations of HMGB1 and/or SDF-1 for inducing migration of cord blood CD34⁺ cells. Freshly isolated cord blood CD34⁺ cells express CXCR4 (SDF-1 receptor), and HMGB1 receptor TLR-2,TLR-4 and RAGE. To explore which receptors were required for the synergy of HGMB1 and/or SDF-1 on cells migration, the anti-SDF-1, anti-CXCR4 and anti-RAGE antibodies were used to detect the effect of HGMB1 alone or with SDF-1 on cord blood CD34⁺ cells migration. The results showed that the purity of CD34⁺ cells isolated from cord blood mononuclear cells by magnetic cell sorting was 97.40 ± 1.26%, the 25 ng/ml SDF-1 did not induce migration of cord blood CD34⁺ cells, whereas the optimal migration was observed at 100 ng/ml. HMGB1 alone did not induce migration up to 100 ng/ml. The dose test found that the the best synergistic concentrations for cells migration were 100 ng/ml HMGB1 combined with 50 ng/ml SDF-1. The blocking test showed that both the anti-SDF-1 (4 µg/ml) and anti-CXCR4 (5 µg/ml) antibodies could block cell migration induced by HMGB1 or combined with SDF-1, but the cord blood CD34⁺ cells in the presence of anti-RAGE, anti-TLR-2 and anti-TLR-4 antibodies did not modify the response to SDF-1 in the presence of HMGB1. It is concluded that both HMGB1 and SDF-1 can induce cord blood CD34⁺ cells migration, HMGB1 enhances SDF-1-induced migration exclusively via CXCR4 and in a RAGE and TLR receptors-independent manner, the exact mechanism needs to be further explored.


Subject(s)
Antigens, CD34 , Metabolism , Cell Movement , Chemokine CXCL12 , Metabolism , Fetal Blood , Cell Biology , Metabolism , Flow Cytometry , HMGB1 Protein , Metabolism , Humans , Receptors, CXCR4 , Metabolism
10.
Journal of Experimental Hematology ; (6): 1698-1701, 2014.
Article in Chinese | WPRIM | ID: wpr-340434

ABSTRACT

The aim of this study was to investigate the role of F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in diagnosis and prognostic evaluation of secondary hemophagocytic syndrome (HPS). A total of 11 secondary HPS patients examined with 18F-FDG-PET/CT were retrospectively analyzed. The diagnostic value of F-18 FDG PET/CT for malignancy detection was assessed. The values of maximum standardized uptake value (SUV(max)) in spleen (SUVS(p)) and in bone marrow (SUVBM) were measured to analyze their relationship with various laboratorial parameters and clinical outcome of secondary HPS patients. The results showed that 4 out of the 11 patients had malignancies, the sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 100%, 66.7% and 75% respectively, the SUV(max) of spleen and bone marrow showed no significant correlation with laboratorial parameters, a maximum SUVS(p) of 3.10 and a maximum SUVBM of 3.47 were the optimal cutoffs for predicting patients' outcome, the increased uptake of F-18 FDG in the BM and spleen were significantly associated with shorter survival time according to univariate analysis. It is concluded that 18F-FDG PET/CT may especially play an important role in diagnosis and predicting outcome of secondary HPS for the small sample size.


Subject(s)
Fluorodeoxyglucose F18 , Humans , Lymphohistiocytosis, Hemophagocytic , Diagnostic Imaging , Multimodal Imaging , Positron-Emission Tomography , Prognosis , Retrospective Studies , Tomography, X-Ray Computed
11.
Chinese Medical Journal ; (24): 2663-2670, 2012.
Article in English | WPRIM | ID: wpr-244375

ABSTRACT

<p><b>BACKGROUND</b>Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.</p><p><b>METHODS</b>All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.</p><p><b>RESULTS</b>The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.</p><p><b>CONCLUSIONS</b>Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.</p>


Subject(s)
Adult , China , Chromosome Aberrations , Chromosomes, Human, Pair 1 , Genetics , Cytogenetic Analysis , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male , Middle Aged , Multiple Myeloma , Genetics , Pathology
12.
Article in Chinese | WPRIM | ID: wpr-263314

ABSTRACT

This study was purposed to investigate the amplification of CD3(-)CD56(+)NK cells in umbilical cord blood and their change of immunophenotype and cytotoxicity after stimulation with IL-2 and IL-15. Mononuclear cells were isolated from umbilical cord blood and cultured in serum-free medium supplemented with IL-2 or (and) IL-15 for 14 d. The subset level of CD3(-)CD56(+)NK cells and expression of CD16, CD62L, NKG2A, NKG2D, NCR44, NCR46, granzyme B and perforin were analyzed by flow cytometry. The cytotoxicity of NK cells to K562 was detected by WST-1 method. The results showed that NK cells stimulated with IL-2, IL-15 and IL-2/IL-15 were amplified by 10.78 ± 2.51, 10.42 ± 3.72, and 10.54 ± 6.24 times respectively after 14 d, there was no statistically significant difference between these three groups. The expression of CD16 decreased obviously in NK cells after amplification; there was significant difference between IL-2 and IL-15 groups. The expression of CD62L was not changed statistically after stimulation with cytokines, the IL-2 down-regulated the expressions of NKG2A and NCR46, while IL-15 showed the opposite effect. IL-2 or IL-15 displayed upregulation effect on the expression of NKG2D, perforin and NCR44, but there was statistically significant difference between effects of these two cytokines. IL-15 up-regulated the expression of granzyme B on NK cells. The cytotoxicity of NK cells stimulated and amplified by cytokines significantly increased, but there was no statistically significant difference between IL-2 and IL-15. It is concluded that IL-2 or IL-15 can effectively amplify umbilical cord blood NK cells under serum-free conditions. Although the immunophenotype associated with NK cells function showed different characteristics between them, however, cytotoxicity of NK cells increased obviously after amplification and there is no statistically significant difference between effect of these two cytokines, their synergistic effect is not obvious. The cytotoxicity of NK cells is the result from combined effect of all active molecules.


Subject(s)
Cells, Cultured , Cytotoxicity, Immunologic , Fetal Blood , Cell Biology , Flow Cytometry , Humans , Immunophenotyping , Interleukin-15 , Pharmacology , Interleukin-2 , Pharmacology , K562 Cells , Killer Cells, Natural
13.
Article in Chinese | WPRIM | ID: wpr-244913

ABSTRACT

This study was aimed to retrospectively analyze and compare the clinical curative efficacy of patients with hematologic malignancies after G-CSF-mobilized sibling HLA-matched (sm) peripheral blood hematopoietic stem cell transplantation (sm-allo-PBHSCT) and sm-allo-PBHSCT combined with bone marrow transplantation (BMT). 100 patients received sm-allo-HSCT in a single center from October 2001 to October to 2010, included 38 patients received sm-allo-PBHSCT and 62 patients received sm-allo-PBHSCT combined with BMT. The myeloablative or reduced intensity conditioning regimens were chosen according to the condition of patients. All patients received standard cyclosporine (CsA) and mycophenolate mofetil (MMF) as prophylaxis for GVHD. The results showed that the rapid hematopoietic reconstitution was observed in all patients. The median time of ANC ≥ 0.5 × 10(9)/L in both groups were 12 days, the median time of platelet count ≥ 20 × 10(9)/L was 15 days in sm-allo-PBHSCT group and 16 days in sm-allo-PBHSCT + BMT group. The incidence of acute GVHD, acute GVHD of III-IV grade and chronic GVHD in sm-allo-PBHSCT and sm-allo-PBHSCT + BMT groups were 37.1% and 34.2%, 7.89% and 8.06%, 36.11% and 41.38% respectively, there were no statistical differences. The relapse rates were similar in two groups (sm-allo-PBHSCT 13.16% vs sm-allo-PBHSCT + BMT 12.9%). The 3-year disease-free survivals in sm-allo-PBHSC and sm-allo-PBHSCT + BMT groups were 57.1 ± 8.7% and 61.3 ± 6.4% respectively (p = 0.852). The 2-year overall survival of high-risk patients was 41.4 ± 12.8% in sm-allo-PBHSCT group, while 60.9 ± 9.6% in sm-allo-PBHSCT + BMT group (p = 0.071). It is concluded that the rhG-CSF mobilized sibling matched allo-PBHSCT + BMT is superior to the rhG-CSF mobilized sibling matched allo-PBHSCT in increasing the overall survival of high-risk hematologic malignancies.


Subject(s)
Adolescent , Adult , Aged , Bone Marrow Transplantation , Child , Child, Preschool , Female , Granulocyte Colony-Stimulating Factor , Therapeutic Uses , HLA Antigens , Allergy and Immunology , Hematologic Diseases , Allergy and Immunology , Therapeutics , Humans , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Retrospective Studies , Siblings , Tissue Donors , Young Adult
14.
Article in Chinese | WPRIM | ID: wpr-244910

ABSTRACT

To investigate the peripheral levels and clinical significance of Th17/Treg cell-associated cytokines in patients with acute graft versus host disease (aGVHD) or chronic GVHD (cGVHD), blood samples were collected from 39 hematopoietic stem-cell transplantation patients and 20 healthy donors. The patients included 10 patients with aGVHD, 13 patients with cGVHD and 16 patients without evidence of GVHD. Th17/Treg cell-associated cytokines such as IFNγ, IL-4, IL-6, IL-10, TGF-β(1), IL-17 and IL-23 were detected by ELISA. The results showed that the plasma levels of IFN-γ, IL-4, IL-6, IL-17 and IL-23 significantly increased in patients with aGVHD or cGVHD, compared with the patients without clinical signs of GVHD and the healthy donors (p < 0.05), while IL-10 and TGF-β(1) were obviously lower than that of them (p < 0.05). After aGVHD and cGVHD patients were treated effectively, the plasma levels of IL-6, IL-17 and IL-23 were significantly decreased, and IL-10, TGF-β(1) were significantly increased, while the levels of IFN-γ and IL-4 did not markedly change. The TGF-β(1) level were negatively correlated with IL-6 (r = -0.36, p < 0.05), IL-17 (r = -0.51, p < 0.05) and IL-23 (r = -0.44, p < 0.05) respectively, while there were positive correlations between IL-6 and IL-17 (r = 0.62, p < 0.05), IL-6 and IL-23 (r = 0.71, p < 0.05), IL-17 and IL-23 (r = 0.93, p < 0.05). It is concluded that Th17/Treg cell-associated cytokines may play an important role in the development of a/cGVHD, which helps to find novel targets for developing new strategies of GVHD treatment.


Subject(s)
Adolescent , Adult , Case-Control Studies , Cytokines , Blood , Female , Graft vs Host Disease , Blood , Humans , Interleukin-10 , Blood , Interleukin-17 , Blood , Interleukin-23 , Blood , Interleukin-6 , Blood , Male , T-Lymphocytes, Regulatory , Metabolism , Transforming Growth Factor beta1 , Blood , Young Adult
15.
Article in Chinese | WPRIM | ID: wpr-244900

ABSTRACT

This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of umbilical cord blood (UCB) CD34(+) cells and to explore the underlying mechanism. The expression of TLR2 and TLR4 on UCB CD34(+) cells was detected with flow cytometry. The effect of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on the migration and adhesion ability of UCB CD34(+) cells was evaluated with chemotaxis and adhesion assays. The results indicated that expression levels of TLR2 and TLR4 were (14.2 ± 3.8)%, (19.6 ± 4.1)% respectively. Compared with the control group, the migration activity of UCB CD34(+) cells toward SDF-1 decreased significantly in LPS group (p < 0.01). The adhesion activity was not altered significantly in LPS group. However, both the migration activity towards SDF-1 and the adhesion activity of UCB CD34(+) cells were not changed significantly in PAM3CSK4 group. Further study found that LPS did not affect the expression level of CXCR4 on CD34(+) cells, but could inhibit the spontaneous migration ability of CD34(+) cells. It is concluded that TLR4 activation can decrease the chemotaxis function of CD34(+) cells towards SDF-1, which may associate with the decreased spontaneous migration ability of CD34(+) cells.


Subject(s)
Antigens, CD34 , Blood , Cell Movement , Cells, Cultured , Chemokine CXCL12 , Fetal Blood , Cell Biology , Allergy and Immunology , Humans , Lipopeptides , Pharmacology , Lipopolysaccharides , Pharmacology , Toll-Like Receptor 2 , Toll-Like Receptor 4
16.
Article in Chinese | WPRIM | ID: wpr-332297

ABSTRACT

The purpose of study was to investigate the cytogenetic abnormality of acute leukemias (AL), to analyze the relationship in the chromosomal abnormality and the AL FAB types, and to explore the impact of the chromosomal abnormalities on the prognostic factors of AL. The chromosome karyotypes of 397 patients with AL were analyzed by means of bone marrow short-term culture and G banding technique. The results showed that in 319 out of 397 patients, the chromosome karyotypes could be analyzed, and the chromosomal abnormality occurred in 175 patients (54.9%). In the patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and acute mixed-lineage leukemia (AMLL), the chromosomal abnormality occurred respectively in 33 of 120 patients (27.5%), 129 of 252 patients (51.2%) and 13 of 25 patients (52.0%). Hyper-diploids, hypo-diploids and diploids occurred in 41 of 175 patients (23.4%), 22 of 175 patients (12.5%), and 112 of 175 patients (64.0%) respectively. In patients with AML the FAB type-associated chromosomal abnormality occurred in 69 of 129 patients (53.5%). It is concluded that chromosomal abnormalities exist in about 55% AL patients. Some special chromosomal abnormalities are cytogenetic characteristics of AL, and obviously correlated with AL FAB types, the combination of chromosomal detection with cytogenetics is useful for the diagnosis of AL, and the evaluation of therapeutic effects and prognosis.


Subject(s)
Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Child , Chromosome Aberrations , Female , Humans , Karyotype , Karyotyping , Leukemia , Genetics , Male , Middle Aged , Young Adult
17.
Chinese Journal of Hematology ; (12): 519-522, 2010.
Article in Chinese | WPRIM | ID: wpr-353599

ABSTRACT

<p><b>OBJECTIVE</b>To analyse the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies.</p><p><b>METHODS</b>Twenty eight consecutive adult patients with hematological malignancies were treated with UCBT and 20 of them were advanced-stage diseases. Double or multiple UCB grafts were used for 18 patients, while single UCB graft for 10 patients. Myeloablative conditioning regimens were given to 26 cases and nonmyeloablative regimens to 2 cases. All patients were given a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.</p><p><b>RESULTS</b>Median time to neutrophil engraftment (≥ 0.5 × 10(9)/L) in 26 patients was 18 (14 - 37) days and platelet engraftment (≥ 20 × 10(9)/L) in 22 patients was 30 (25 - 49) days. Chimerism was weekly assessed by PCR analysis of short tandem repeat (STR) sequences in whole blood or bone marrow and 22 cases were confirmed of fully donor chimeric from 7 to 21 days after transplantation. Eighteen cases developed acute GVHD, greater than grade II in 1, and 6 of 22 patients who survived more than 100 days developed limited chronic GVHD. Eighteen cases were alive in hematologic remission at a median follow-up of 9.5 (2.5 - 72.0) months. The probability of event-free survival at 3 years was 56.7%. Two cases relapsed and 8 of 10 cases died of transplant related complications.</p><p><b>CONCLUSIONS</b>UCBT could be safely and effectively used for adult patients with hematologic malignancies. Use of double UCB units is a strategy extending the feasibility of UCBT.</p>


Subject(s)
Adult , Fetal Blood , Graft vs Host Disease , Hematologic Neoplasms , Therapeutics , Hematopoietic Stem Cell Transplantation , Humans , Transplantation Conditioning
18.
Journal of Experimental Hematology ; (6): 1302-1305, 2010.
Article in Chinese | WPRIM | ID: wpr-332372

ABSTRACT

This study was purposed to evaluate the sensitivity and specificity of G/(1, 3-β-D glucan)/GM (galactomannan) combined detection for early diagnosis of invasive fungal disease (IFD), determine the GM positive cut-off value, and investigate the change of diagnostic level before and after G/GM test and the relation of GM value with therapeutic effect. The ELISA with double antibody sandwich was used to detect the serum levels of G and G/M. The results showed that according to determined GM positive cut-off value, the sensitivity, specificity, positive and negative predictive value of G/GM combined detection were 100%, 65.7%, 67.6% and 100%, respectively. The case number of the clinical diagnosis of IFD increased from 1 to 24 cases, the diagnosis of 12 non-infective patients was changed as suspected IFD with the help of G/GM combined detection; the GM cut-off value decreased in patients whose GM cut-off value was higher before therapy and antifungal therapy was effective, while the GM cut-off value increased in patients no-responded to therapy. It is concluded that G/GM combined detection can increased the sensitivity of the diagnosis and reduce false negative rate in the early diagnosis of IFD. The dynamically monitoring G/GM cut-off value can be used as evaluation indicator of therapeutic efficacy.


Subject(s)
Adolescent , Adult , Aged , Antigens, Fungal , Child , Child, Preschool , Early Diagnosis , Female , Hematologic Neoplasms , Microbiology , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Mycoses , Diagnosis , Allergy and Immunology , Sensitivity and Specificity , Young Adult
19.
Article in Chinese | WPRIM | ID: wpr-243340

ABSTRACT

This study was aimed to explore the immune escaping mechanisms based on expression and abscission of human natural killer (NK) cell activating receptors NKG2D and their ligands MICA/B, ULBP-1, 2, 3 in patients with acute leukemia (AL). 30 de novo AL patients and 10 healthy persons (control) were enrolled in study. Flow cytometry was used to detect the expression levels of MICA/B, ULBP-1, 2, 3 on leukemic cells. ELISA was used to detect the levels of soluble MICA (sMICA), solube MICB (sMICB) and soluble ULBP-1, -2, -3 in the serum. The results showed that sMICA, sMICB and ULBP-1, -2, -3 were not expressed or expressed at very low levels on leukemia cells of the patients; the levels of free sMICA and sMICB in serum of AL patients were higher than that in serum of healthy persons, there was significant difference (p<0.01). But the levels of ULBP 1-3 in serum of AL patients did not show obvious statistical difference as compared with healthy persons (p>0.05). It is concluded that the negative or low expression of NKG2D ligands (MICA, MICB and ULBPs) on surface of acute leukemia cells may lead to the immune escape of leukemia cells, the abscission of MICA and MICB, and the deficiency of ULBP expression on leukemia cells may be one of immune escape mechanisms of leukemia cells.


Subject(s)
Case-Control Studies , Female , Flow Cytometry , GPI-Linked Proteins , Allergy and Immunology , Metabolism , Gene Expression Regulation, Leukemic , Histocompatibility Antigens Class I , Allergy and Immunology , Metabolism , Humans , Intercellular Signaling Peptides and Proteins , Allergy and Immunology , Metabolism , Intracellular Signaling Peptides and Proteins , Allergy and Immunology , Metabolism , Leukemia , Blood , Allergy and Immunology , Male , NK Cell Lectin-Like Receptor Subfamily K , Allergy and Immunology , Metabolism , Tumor Escape
20.
Article in Chinese | WPRIM | ID: wpr-243338

ABSTRACT

This study was aimed to investigate the function defect of partial homing receptor on cord blood hematopoietic stem cells (CBHSC) and explore efficacy and feasibility of intervention in vitro. The expression and activity of active groups in P, E-selectin ligands on CD34+ cells from cord blood, bone marrow and peripheral blood were detected by flow cytometry; meanwhile the expression of active groups in selectin ligands on CD34+ cells treated by fucosyl transferase in vitro was determined by flow cytometry. The results indicated that the expression levels of CD26 on the surface of stem/progenitor cells (CD34+) from cord blood, bone marrow and peripheral blood were (7.62+/-0.63)%, (6.35+/-0.89)% and (6.18+/-0.91)% (p>0.05) respectively. And the activities of CD26 of the three sources of stem cells were 67.15 U/1000 cells (1 U=1 pmol/min), 26.85 U/1000 cells and 20.95 U/1000 cells respectively, in which the activity of CD26 on surface of CD34+ from cord blood was significantly higher than that from other both sources (p<0.01). The expression levels of P-selectin ligand on the stem/progenitor cells three kinds were (83.46+/-6.33)%, (15.65+/-0.89)% and (80.17+/-6.85)%, and the expression levels of E-selectin ligand on stem/progenitor cells of three kinds were (25.31+/-1.03)%, (26.34+/-0.89)% and (29.79+/-1.78)% respectively. The expression of E-selectin ligand on the surface of cord blood stem/progenitor cell CD34+ increased from (25.31+/-1.03)% to (63.23+/-1.08)% after glycosylation engineering. It is concluded that there is no significant difference of the expression of CD26 between the three sources of stem/progenitor cells, but the activity of CD26 in cord blood was obviously higher than that in bone marrow and peripheral blood. The expression of P-selectin ligand on bone marrow stem/progenitor cell was lower than that on stem cells of cord blood and peripheral blood. Glycosylation engineering can promote and elevate the expression of E-selectin ligand on the surface of CD34+ cells from cord blood.


Subject(s)
Antigens, CD34 , Metabolism , Bone Marrow Cells , Cell Biology , Metabolism , Cells, Cultured , Dipeptidyl Peptidase 4 , Metabolism , Fetal Blood , Cell Biology , Hematopoietic Stem Cells , Cell Biology , Metabolism , Humans , Receptors, Fibroblast Growth Factor , Metabolism , Sialoglycoproteins , Metabolism , Stem Cells , Cell Biology , Metabolism
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