-
[show abstract]
[hide abstract]
ABSTRACT: Mixed-lineage acute leukemia (MAL) is characterized as acute leukemia involving acute myeloid cells and lymphoid cells at the same time. It is easily misdiagnosed because of the dual characteristics involving both lymphoid and myeloid cells and has a poor prognosis. We retrospectively analyzed the features and treatment effectiveness in a single center in 40 patients with MAL. The morphology was consistent with acute lymphoblastic leukemia (ALL) (47.5%) or acute myeloid leukemia (AML) (20%) or was inconclusive (32.5%). Twenty-two patients were characterized as B/myeloid, and 18 patients as T/myeloid. Cytogenetics showed t(9;22)/(Ph(+)) (12.5%) and 11q23/MLL rearrangements (6.25%). The rate of first complete remission for patients undergoing chemotherapy based on the features of both ALL and AML and of either ALL or AML was 71.4 and 42.9%, respectively. The 1-year overall survival rates were 37.5 and 60.0% for chemotherapy and chemotherapy followed by haploidentical hematopoietic stem cell transplantation (HSCT), respectively. The 1-year disease-free survival rates were 25.0 and 50.0% for chemotherapy and chemotherapy followed by HSCT, respectively. These results showed that MAL is confirmed to be a poor-risk disease. The chemotherapy for remission induction should be based on both myeloid cells and lymphoid cells. Transplantation should be performed after the first remission.
Hematology (Amsterdam, Netherlands) 03/2013; · 1.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Unmanipulated HLA-haploidentical/mismatch related transplantation with combined granulocyte-colony stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilized bone marrow (G-BM) has been used as an alternative transplantation strategy for patients without an HLA-matched donor. In this transplantation setting, factors associated with hematopoietic recovery have not been defined completely. The aim of this study was to investigate the factors influencing the engraftment in this transplantation setting for patients with leukemia. The study group comprised 104 patients with leukemia who underwent transplantation at a single institution between 2005 and 2008. Factors correlating with neutrophil and platelet engraftment post-transplantation were analyzed retrospectively. All patients achieved an absolute neutrophil count of 500/μL with a mean time of 13.6days (range 8-20days) and a platelet count over 20×10(9)/L with a mean time of 20.2days (range 16-26days). In univariate analysis, donor and age were associated with increased risk of neutrophil engraftment, but their significance was lost upon multivariate analysis. The sex, age, donor, CD34(+) cell dose, conditioning regimen, mismatched locus, ABO mismatched and diagnosis have no effect on platelet engraftment. Our results suggest that it is an ideal approach to treat patients with leukemia with HLA-haploidentical/mismatched related transplantation with combined G-PBSCs and G-BM for a high level of stem cells without delayed engraftment.
Transfusion and Apheresis Science 06/2011; 44(3):249-55. · 1.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Human umbilical cord blood-derived stromal cells (hUCBDSC) comprise a novel population of CD34(+) cells that has been isolated in our laboratory. They have been shown previously not only to be non-immunogenic but also to exert immunosuppressive effects on xenogenic T cells in vitro. This study investigated the role of hUCBDSC in immunomodulation in an acute graft-versus-host disease (GvHD) mouse model after haplo-identical stem cell transplantation.
Acute GvHD was induced in recipient (B6 × BALB/c)F(1) mice by irradiation (750 cGy) followed by infusion of bone marrow cells and splenocytes from donor C57BL/6 mice. hUCBDSC were co-transplanted in the experimental group. The survival time, body weight and clinical and histopathologic scores were recorded after transplantation. The expression of surface markers [major histocompatibility complex (MHC) I, MHC II, CD80 and CD86] on CD11c(+) dendritic cells (DC), and the percentage of CD4(+) regulatory T cells (Treg), in the spleens of recipient mice were examined by flow cytometry.
The survival time was significantly prolonged, and the clinical and histopathologic scores were reduced in mice co-transplanted with hUCBDSC. The expression levels of the surface markers on DC were significantly lower in mice transplanted with hUCBDSC compared with those without. The proportion of CD4(+) Treg in the spleen was also increased in mice transplanted with hUCBDSC.
These results from a GvHD mouse model are in agreement with previous in vitro findings, suggesting that hUCBDSC possess immunosuppressive properties and may act via influencing DC and CD4(+) Treg.
Cytotherapy 01/2011; 13(1):83-91. · 3.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Human umbilical cord blood derived stromal cells (hUCBDSCs), a novel resource isolated by our laboratory, have been shown to exert an immunologic regulation. Very late activation antigen-4 (VLA-4) has been associated with graft-versus-host disease (GVHD). This study aimed to investigate the possible mechanism by in vitro co-cultured splenocytes of donor mice with hUCBDSCs and in haploidentical stem cell transplantation in mice with acute GVHD. Both hUCBDSCs and human bone marrow stromal cells (hBMSCs) elicited decreased lymphocyte expression of VLA-4, but this decrease was stronger with hUCBDSCs than with hBMSCs (p<0.05). Cotransplantation of bone marrow with hUCBDSCs significantly decreased the expression of VLA-4 compared with control mice (p<0.05). A significant reduction of VLA-4 labeling in the target organs of GVHD was evident in haploidentical mice cotransplanted with hUCBDSCs. Our study shows that hUCBDSCs may protect mouse recipients of haploidentical stem cell transplantation from aGVHD via downregulating the expression of VLA-4.
Clinical Immunology 01/2011; 139(1):94-101. · 4.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Unmanipulated HLA-haplo identical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilized bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients without an HLA-matched related or unrelated donor. In this transplantation setting, the cost and outcome of stem cell collections have not been defined completely. The aim of this study was to compare the cost and outcome of stem cell collection in HLA-haplo identical/mismatched related transplantation with combined G-PBSCs and G-BM to the HLA-identical/matched transplantation with G-PBSCs alone for patients with hematologic malignancies. Hundred and fifty-two healthy donors received twice-daily granulocyte-colony stimulating factor (G-CSF) subcutaneously for 5 days. The PBSCs were collected on day 4 and 5 of G-CSF treatment for HLA-identical/matched transplantation from unrelated/related donors. The PBSC collections and BM harvests was performed on day 4 and 5 of G-CSF treatment for HLA-haplo identical/mismatched related transplantation from related donors, respectively. There was no difference in the major characteristics between groups. More stem cells were harvested in HLA-haplo identical/mismatched related donors than that of HLA-identical/matched donors and a lower cost was seen in the former. The HLA-haplo identical/mismatched related transplantation with combined G-PBSCs and G-BM was a feasible approach with high cell harvest and low cost of stem cell collection for patients with hematologic malignancies.
Transfusion and Apheresis Science 08/2010; 43(1):23-8. · 1.25 Impact Factor
-
Lei Hao,
Cheng Zhang,
Xing-Hua Chen,
Zhong-Min Zou,
Xi Zhang,
Pei-Yan Kong,
Xue Liang,
Lei Gao,
Xian-Gui Peng, Ai-Hua Sun,
Qing-Yu Wang
[show abstract]
[hide abstract]
ABSTRACT: To explore immunological properties of human umbilical cord blood-derived stromal cells (hUCBDSC) and their effect on xenogeneic immune cells in vitro.
Immunological phenotype of freshly isolated and cryopreserved hUCBDSCs was evaluated by flow cytometry. Xenogeneic splenic T-cells were stimulated by phytohemaglutinin A (PHA) or dendritic cells in the absence or presence of hUCBDSCs. T-cell proliferation was measured by cell counting kit-8 after 7-day incubation. The proportion of apoptotic cells and CD4+CD25+Foxp3+ regulatory T-cells (Tregs) was determined in T-cells activated by PHA in the absence or presence of hUCBDSCs by flow cytometry. Phenotype of dendritic cells, cultured alone or with hUCBDSCs, was analyzed by flow cytometry.
Levels of immune molecule expression on freshly isolated hUCBDSCs were as follows: human leukocyte antigen-I (HLA-I) (84.1+/-2.9%), HLA-II (1.6+/-0.3%), CD80 (0.8+/-0.1%), CD86 (0.8+/-0.1%), CD40 (0.6+/-0.1%), and CD40L (0.5+/-0.1%), which was not influenced by cryopreservation. T-cell proliferation in the presence of hUCBDSCs was significantly lower than that of positive control. The coculture led to a 10-fold increase (from 1.2+/-0.3% to 12.1+/-1.4%, P<0.001) in the proportion of CD4+CD25+Foxp3+ regulatory T-cells (Tregs) and a reversion of mature dendritic cells, as indicated by the down-regulation of major histocompatibility complex (MHC)-II molecule (49.3% vs 25.9%, P=0.001), CD80 (47.2% vs 23.3%, P=0.001), and CD86 (40.6% vs 25.1%, P=0.002). When subjected to annexin V binding and propidium iodide uptake assay, the hUCBDSCs did not show the ability to induce apoptosis of xenogeneic T-cells.
These results demonstrate low immunogenicity and immunomodulation effect of the hUCBDSCs. Reversion of mature dendritic cells and increase in Treg proportion, but not cell apoptosis, can possibly contribute to the suppression of xenogeneic T-cell proliferation by the hUCBDSCs.
Croatian Medical Journal 09/2009; 50(4):351-60. · 1.80 Impact Factor
-
Xing-Hua Chen,
Lei Gao,
Xi Zhang,
Li Gao,
Cheng Zhang,
Pei-Yan Kong,
Hong Liu,
Xian-Gui Peng, Ai-Hua Sun,
De-Guang Qi,
Yi Gong,
Qing-Yu Wang
[show abstract]
[hide abstract]
ABSTRACT: We present an update of our results regarding related HLA-haploidentical and HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in patients with leukemia. We compared the outcomes of 107 patients with leukemia undergoing HLA-identical sibling (n=51) or related HLA-haploidentical (n=56) HSCT performed during the same time period. Patients received BU-CY/CY-TBI in HLA-identical sibling HSCT or TBI+Ara-C+CY+ATG/CCNU+Ara-C+Bu+CY+ATG in haploidentical HSCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidence of grades II through IV acute graft-versus-host disease (aGvHD) in the matched and haploidentical cohorts was 13.7% and 26.8% (P<0.05), respectively. The risk of developing cGvHD was not different between HLA-matched and haploidentical patients (P>0.05). The two-year incidence of treatment-related mortality for matched and haploidentical patients was 7.8% and 12.5%, respectively, with P>0.05, and the incidence of relapse was 17% and 22%, respectively, with P>0.05. The two-year adjusted leukemia-free survival for matched versus haploidentical patients was 76% and 68%, respectively, with P>0.05, and the overall survival for matched versus haploidentical patients was 80% and 70%, respectively, with P>0.05. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia were related to increased risk of relapse, treatment failure, and overall mortality. In summary, HSCT performed with related HLA-haploidentical donors is a feasible approach with acceptable outcomes.
Blood Cells Molecules and Diseases 05/2009; 43(1):98-104. · 2.35 Impact Factor
-
Xing-hua Chen,
Cheng Zhang,
Xi Zhang,
Li Gao,
Lei Gao,
Pei-yan Kong,
Xian-gui Peng,
De-guang Qi, Ai-hua Sun,
Dong-feng Zeng,
Hong Liu,
Yi Gong,
Qing-yu Wang
[show abstract]
[hide abstract]
ABSTRACT: The main obstacle for allogeneic transplantation is delayed hematologic reconstitution and serious graft-versus-host disease (GVHD). The results of 128 patients with hematologic malignancies undergoing HLA-identical (n=52) or HLA-haploidentical/mismatched (n=76) hematopoietic stem cell transplantation (HSCT) performed during the same time period were compared. Patients with HLA-identical HSCT received unmanipulated granulocyte-colony stimulating factor-mobilized peripheral blood stem cells (G-PBSCs). Forty-six patients with HLA-haploidentical related HSCT received antithymocyte globulin (ATG) in conditioning regimens followed by the transplantation of the combination of unmanipulated G-PBSCs and granulocyte-colony stimulating factor-mobilized bone marrow (G-BM) and 30 patients with HLA-mismatched unrelated HSCT received ATG in conditioning regimens followed by the transplantation of unmanipulated G-PBSCs. All patients got successful hematopoietic engraftment. The cumulative incidences of grades I to II acute GVHD (aGVHD) on day 100 in the identical, haploidentical related and mismatched unrelated cohorts were 21.2%, 43.5%, and 53.3%, respectively. The cumulative incidences of chronic GVHD (cGVHD) in the identical, mismatched unrelated, and haploidentical related cohorts were 34.6%, 33.3%, and 10.9%, respectively. The 2-year relapse and treatment-related mortality (TRM) rates were 19.2%, 23.9%, 23.3%, and 9.6%, 8.7%, 10% for patients who underwent identical, HLA-haploidentical related, and mismatched unrelated transplantation, respectively. The 2-year probabilities of leukemia-free survival and overall survival were 72.2%, 70.6%, 68.1%, and 76.5%, 77.8%, 70.0% after identical, haploidentical related and mismatched unrelated transplantations, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of disease had increased risk of relapse, treatment failure, and overall mortality. In conclusion, it is a feasible approach with acceptable outcomes for patients undergoing HLA-haploidentical related HSCT by the combination of G-PBSCs and G-BM with conditioning regimens including ATG.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2009; 15(2):266-73. · 3.15 Impact Factor
-
Lei Hao,
Cheng Zhang,
xhchen888@yahoo.com.cn,
Zhong-Min Zou,
Xi Zhang,
Pei-Yan Kong,
Xue Liang,
Lei Gao,
Xian-Gui Peng, Ai-Hua Sun,
Qing-Yu Wang
[show abstract]
[hide abstract]
ABSTRACT: Aim To explore immunological properties of human umbilical cord blood-derived stromal cells (hUCBDSC) and their effect on xenogeneic immune cells in vitro. Methods Immunological phenotype of freshly isolated and cryopreserved hUCBDSCs was evaluated by flow cytometry. Xenogeneic splenic T-cells were stimulated by phytohemaglutinin A (PHA) or dendritic cells in the absence or presence of hUCBDSCs. T-cell proliferation was measured by cell counting kit-8 after 7-day incubation. The proportion of apoptotic cells and CD4+CD25+Foxp3+ regulatory T-cells (Tregs) was determined in T-cells activated by PHA in the absence or presence of hUCBDSCs by flow cytometry. Phenotype of dendritic cells, cultured alone or with hUCBDSCs, was analyzed by flow cytometry. Results Levels of immune molecule expression on freshly isolated hUCBDSCs were as follows: human leukocyte antigen-I (HLA-I) (84.1 ± 2.9%), HLA-II (1.6 ± 0.3%), CD80 (0.8 ± 0.1%), CD86 (0.8 ± 0.1%), CD40 (0.6 ± 0.1%), and CD40L (0.5 ± 0.1%), which was not influenced by cryopreservation. T-cell proliferation in the presence of hUCBDSCs was significantly lower than that of positive control. The coculture led to a 10-fold increase (from 1.2 ± 0.3% to 12.1 ± 1.4%, P < 0.001) in the proportion of CD4+CD25+Foxp3+ regulatory T-cells (Tregs) and a reversion of mature dendritic cells, as indicated by the down-regulation of major histocompatibility complex (MHC)-II molecule (49.3% vs 25.9%, P = 0.001), CD80 (47.2% vs 23.3%, P = 0.001), and CD86 (40.6% vs 25.1%, P = 0.002). When subjected to annexin V binding and propidium iodide uptake assay, the hUCBDSCs did not show the ability to induce apoptosis of xenogeneic T-cells. Conclusion These results demonstrate low immunogenicity and immunomodulation effect of the hUCBDSCs. Reversion of mature dendritic cells and increase in Treg proportion, but not cell apoptosis, can possibly contribute to the suppression of xenogeneic T-cell proliferation by the hUCBDSCs.
Croatian Medical Journal (cmj@mef.hr); Vol.50 No.4.
