Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
Br J Haematol ; 204(6): 2351-2364, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38613241

ABSTRACT

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.


Subject(s)
Antigens, CD7 , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Remission Induction , Humans , Male , Female , Hematopoietic Stem Cell Transplantation/methods , Adult , Adolescent , Middle Aged , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Young Adult , Child , Recurrence , Transplantation, Homologous , Receptors, Chimeric Antigen/therapeutic use , Treatment Outcome , Child, Preschool , Survival Rate
2.
Front Immunol ; 14: 1191382, 2023.
Article in English | MEDLINE | ID: mdl-37469510

ABSTRACT

Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival. Methods: A single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy. Results: The median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021). Conclusions: Our study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.


Subject(s)
Burkitt Lymphoma , Hematopoietic Stem Cell Transplantation , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Humans , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Immunotherapy, Adoptive , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Acute Disease , Neoplasm, Residual
3.
Leuk Lymphoma ; 63(14): 3307-3316, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36067518

ABSTRACT

We retrospectively analyzed the outcomes of 240 pediatric SAA patients who underwent unmanipulated alternative HSCT between September 2012 and November 2020 at our center. The incidence of GF (PGF + SGF) was higher in the UCBD cohort compared to the MUD and HID cohorts [(13.5% ± 6.5%) vs (0%), and (1.6% ± 5.3%), respectively, p = .0001]. The incidence of platelet engraftment within 180 days post-HSCT was lower in the UCBD cohort (82.4% ± 2.3%) compared to the HID group (96.2% ± 1.3%) and the MUD group (97.4% ± 0.5%) (p = .020). the median duration time for platelet engraftment in the UCBD cohort was 29 days, longer than in HID cohort 14 days and the MUD cohort 13 days (p = .005). UCBD cohort had a lower 3-year failure-free survival (FFS) (70.5% ± 8.4%) compared to the HID cohort (81.1% ± 4.3%) and the MUD cohort (92.5% ± 3.1%) (p = .030) and lower 3-year GVHD/relapse free survival (GRFS) (63.3% ± 9.5.4%) compared to the HID cohort (75.5% ± 6.8%) and MUD cohort (87.9% ± 4.5%) (p = .002). UCBD-HSCT had inferior FFS and GRFS compared to an HSCT with an HID or MUD in pediatric patients with acquired SAA. A UCBD-HSCT had a higher GF and lower incidence of platelet engraftment and longer platelet engraftment time.


Subject(s)
Anemia, Aplastic , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Child , Humans , Unrelated Donors , Retrospective Studies , Blood Donors , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Recurrence , Transplantation Conditioning
5.
Front Immunol ; 13: 1066748, 2022.
Article in English | MEDLINE | ID: mdl-36685540

ABSTRACT

Introduction: We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1). Methods: We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021. Results: The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT. Conclusions: Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.


Subject(s)
Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Humans , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Prognosis , Retrospective Studies , Transplantation, Homologous , Neoplasm Recurrence, Local/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematologic Neoplasms/therapy , Chronic Disease
6.
Front Immunol ; 12: 605766, 2021.
Article in English | MEDLINE | ID: mdl-34025637

ABSTRACT

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% vs. 37%; p<0.01) and more with complex cytogenetics (44% vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft-versus-host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% vs.11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs.11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.


Subject(s)
Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Antigens, CD19 , Antigens, Neoplasm , Child , Combined Modality Therapy , Drug Resistance, Neoplasm , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Male , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , Recurrence , Retreatment , Transplantation, Homologous , Treatment Outcome , Young Adult
7.
Hematology ; 26(1): 134-143, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33491597

ABSTRACT

Objective: The outcomes of alternative donor hematopoietic stem cell transplantation (HSCT) with unmanipulated grafts for Inherited bone marrow failure syndromes (IBMFS) are discouraging. Our study is to demonstrate that IBMFS with disease-specific characteristics requires a tailored conditioning regimens to enhance engraftment and reduce regimen related toxicities. Methods: We retrospectively analyzed 42 patients diagnosed with IBMFS and transplanted with an alternative donor graft at our center from November 2012 to August 2018. Twenty-seven patients had Fanconi anemia (FA), 7 had dyskeratosis congenita (DC), and 8 had severe congenital neutropenia (SCN). Patients received ex-vivo unmanipulated alternative donor grafts from a matched unrelated donor (MUD) (n = 22), haploidentical donor (HID) (n = 17) and unrelated cord blood donor (UCBD) (n = 3). FA and DC patient subgroups received reduce intensified conditioning (RIC), while SCN patients received a myeloablative conditioning (MAC) regimen. Results: The median follow-up time for the surviving patients was 38 months (range: 9-63 months). The failure-free survival (FFS) for entire cohort was 76.1%, and was 72.4%, 100% and 56.2% for patients with FA, DC and SCN, respectively. There were no primary graft failures. The cumulative incidence of aGVHD at day 100 was 48.1%. The cumulative incidence of cGVHD at 1 and 3 years was 35.0% and 69.3%, respectively. Conclusion: HSCT using alternative donors with unmanipulated grafts and disease-specific conditioning regimens for IBMFS patients shows promising survival.


Subject(s)
Congenital Bone Marrow Failure Syndromes/therapy , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Graft Survival , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Survival Analysis , Transplantation Conditioning/adverse effects , Unrelated Donors , Young Adult
8.
Ann Hematol ; 100(6): 1579-1591, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33236196

ABSTRACT

There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.


Subject(s)
Busulfan/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Myeloablative Agonists/therapeutic use , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Remission Induction , Retrospective Studies , Siblings , Tissue Donors , Transplantation Conditioning/methods , Treatment Outcome , Unrelated Donors , Young Adult
9.
Ann Hematol ; 99(12): 2911-2925, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33000361

ABSTRACT

Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Living Donors , Siblings , Transplantation, Haploidentical/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/trends , Histocompatibility Testing/methods , Histocompatibility Testing/trends , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Recurrence , Retrospective Studies , Transplantation Conditioning/methods , Transplantation Conditioning/trends , Transplantation, Haploidentical/trends , Treatment Outcome , Young Adult
10.
Huan Jing Ke Xue ; 41(3): 1474-1481, 2020 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-32608651

ABSTRACT

The North China Plain is an important grain production area in China. Due to the low content of soil organic carbon, increasing the application rate of nitrogen fertilizer would not lead to a continuous increase of maize yield at present. The combined application of organic fertilizer and inorganic fertilizer is widely regarded as a measure to simultaneously increase grain yield and soil organic carbon; however, the effect of organic fertilizer and inorganic fertilizer application on N2O emissions from farmland in the North China Plain is unclear. Here, N2O emissions and crop yields in cropland under the combined application of different types and rates of organic fertilizers plus inorganic N fertilizer were measured in the North China Plain. The field experiment included eight treatments:no N fertilizer (CK), inorganic fertilizer (NPK), 40% cow manure N plus 60% inorganic fertilizer N (CM), 40% chicken manure N plus 60% inorganic fertilizer N (FC), 40% pig manure N plus 60% inorganic fertilizer N (FP), 20% cow manure N plus 80% inorganic fertilizer N (1/2CM), 20% chicken manure N plus 80% inorganic fertilizer N (1/2FC), and 20% pig manure N plus 80% inorganic fertilizer N (1/2FP). The N2O fluxes were significantly correlated with soil water-filled pore space during the maize season (P<0.05). There was a significant linear relationship between N2O fluxes and soil dissolved organic carbon content during the maize season in all treatments except the NPK treatment. In the maize season, N2O emission was 0.50 kg·hm-2 under CK treatment, and increased to 2.28 kg·hm-2 under NPK treatment. However, when the proportion of manure N to total N applied was reduced from 40% to 20%, N2O emissions were significantly reduced by 33.6%, 43.7%, and 12.1% under 1/2CM, 1/2FC, and 1/2FP treatments, respectively. The difference in application rate of organic manure N did not significantly affect maize yield. The reduction of N2O emission at the low manure application rate compared with the high manure application rate was likely due to the decrease in dissolved organic carbon in soils.

11.
Biol Blood Marrow Transplant ; 24(9): 1881-1887, 2018 09.
Article in English | MEDLINE | ID: mdl-29772350

ABSTRACT

Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P = .001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P = .045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P = .129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P = .198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P = .210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P = .127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P = .976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA.


Subject(s)
Anemia, Aplastic/therapy , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Haploidentical/methods , Adolescent , Adult , Anemia, Aplastic/pathology , Child , Child, Preschool , Female , Humans , Male , Treatment Outcome , Unrelated Donors , Young Adult
12.
Ying Yong Sheng Tai Xue Bao ; 27(3): 993-1101, 2016 Mar.
Article in Chinese | MEDLINE | ID: mdl-29726207

ABSTRACT

Coastal wetlands contribute about 75% to the global oceanic CH4 emissions, thus play a vital role in global C cycles. In this paper, we provided a perspective on researches on metabolic, phylogenetic, and ecological diversity of the methanogenic archaea and the regulating environmental factors in coastal wetlands. Because of the presence of more favorable electron acceptors such as sulfate, methanogenesis via CO2 reduction and acetate fermentation are limited by availability of substrates, and hydrogenotrophic and acetotrophic methanogens generally express low relative abundance. In contrast, "non-competitive" substrates such as methanol and methylated compounds have been shown to contribute substantially to methane formation in coastal wetlands, and the facultative methanogens are predominant in those environments. Salinity regulates vegetation zonation and is related to SO42- concentration, by regulating types of methanogenic substrates and contents of compe-titive electron acceptors, indirectly affects the structure and function of methanogens. Major uncertainties in the current studies include the following: methanogen community structure, the key environmental factors regulating methane pathway, and their effects on methane emissions in coastal wetlands.


Subject(s)
Archaea/classification , Methane/analysis , Wetlands , Archaea/metabolism , Environmental Monitoring , Phylogeny , Salinity
13.
Clin Transpl ; : 245-50, 2014.
Article in English | MEDLINE | ID: mdl-26281152

ABSTRACT

Published reports suggest that engraftment failure after hematopoietic stem cell transplantation (HSCT) is closely associated with the presence of donor-specific HLA antibodies (DSA). Herein, we report a single cohort retrospective analysis of 567 cases of HLA mismatched allogeneic HSCT patients from the Lu Dao-pei Hematology Center, transplanted between September 11, 2012, and November 20, 2014. Of these cases, 306 patients underwent HLA class I and II antibody testing within one month before transplantation. For patients with HLA antibody screening resulting in an HLA antibody with a mean fluorescence intensity (MFI) > 1000, single antigen bead HLA class I and II testing was performed. Then, according to donor HLA genotype, we determined whether DSA were present. Of the 306 patients with pre-transplant HLA antibody screening (LABScreen Mixed Antigen), HLA class I antibodies were present in 51 cases (16.7%). HLA class II antibodies were present in 24 cases (7.8%). Of all antibody positive cases, 20 cases were positive for HLA antibodies on single antigen beads at an MFI > 1000. Half of these cases were DSA positive. Of the non-DSA antibody cases (n = 1 0), there was one case of primary graft failure after HSCT. In the ten DSA positive patients, the HSCT was chosen from the reactive donor. Seven of these cases were treated prior to HSCT with 1-2 times plasmapheresis or high-dose intravenous immunoglobulin (IVIG) therapy. The other three cases had no special treatment to decrease HLA antibodies before transplantation. All 10 DSA positive cases achieved successful engraftment. There was one case of primary graft failure in the group of 273 patients who were HLA antibody negative. Out of the group of 261 patients who did not undergo HLA antibody screening, there were 7 cases of primary engraftment failure. The incidence of engraftment failure was lower in the group of patients who had been screened for HLA antibodies prior to transplant than it was for the patients who had not been screened (2/306 versus 7/261, p = 0.054). Five of the 7 cases of engraftment failure were screened for HLA antibodies at 30 days after first transplantation. The results of five of the cases were negative for HLA antibodies and the patients underwent second transplants, all achieving successful engraftment. This cohort researched HLA antibodies and their effect on engraftment of HSCT in Chinese cases. We compared 306 patients who underwent HLA antibody screening and were given the appropriate treatment before HSCT if DSA were positive, with 261 patients who were not screened for HLA antibodies. We found that the incidence of primary graft failure significantly decreased. Although not directly determined, HLA antibodies (especially DSA) are the cause of engraftment failure and our findings reflect the importance of HLA antibody screening prior to transplantation. We suggest that patients with pre-existing DSA should be treated with plasma exchange or IVIG therapy before transplantation.


Subject(s)
HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation , Histocompatibility , Isoantibodies/blood , Adolescent , Adult , Biomarkers/blood , China , Desensitization, Immunologic/methods , Graft Survival , Hematopoietic Stem Cell Transplantation/adverse effects , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Plasmapheresis , Predictive Value of Tests , Reoperation , Retrospective Studies , Risk Factors , Time Factors , Transplantation, Homologous , Treatment Failure , Young Adult
14.
Zhonghua Xue Ye Xue Za Zhi ; 32(7): 445-9, 2011 Jul.
Article in Chinese | MEDLINE | ID: mdl-22213862

ABSTRACT

OBJECTIVE: To analyze the clinical and laboratory features of 9 cases of gammadeltaT cell lymphoma or leukemia. METHODS: From 2007 to 2011, 9 patients with gammadeltaT-cell lymphoma/leukemia were diagnosed in our hospital. The immunophenotype of the abnormal cells were detected by flow cytometry, clonal gene rearrangement of IgH, TCRgamma, TCRdelta by PCR, chromosome karyotype analysis by G banding, acute leukemia gene and the DNA of type 1 - 8 human herpes virus by multiple nested PCR, The gammadeltaT cells were determined by T cell with TCR gammadelta chain, the malignant gammadelta T cells by the abnormal expression of T cell antigens and the precursor malignant gammadelta T cells by the expression of CD34, TDT, CD99, CD1 a or acute leukemia genes. RESULTS: In the 9 patients with gammadeltaT cell lymphoma leukemia, significant malignant gammadeltaT cells infiltration of bone marrow were found in 8 with blast morphology. 5 were diagnosed as T-ALL/LBL (gammadeltaT type) and 4 HSgammadelta TCL. The clonal gene rearrangement of TCRgamma and/or TCRB were detected in 6/6 patients. Patients either did not achieve complete remission(CR) after induction therapy or relapsed quickly after CR. Only 4/5 patients remained continuous CR(CCR) at 2, 2, 3,12 months respectively, after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the fifth T-ALL (gammadeltaT) relapsed 1 month after allo-HSCT. CONCLUSIONS: The incidence of gammadelta T cell lymphoma or leukemia may be higher than reported, part of them were T-ALL/LBL with poor prognoses. FCM and clonal gene rearrangement of TCRgamma and/or TCRdelta are helpful to diagnosis. Allo-HSCT may be the only curative approach.


Subject(s)
Leukemia, T-Cell/genetics , Lymphoma, T-Cell/genetics , Receptors, Antigen, T-Cell, gamma-delta/genetics , Adolescent , Adult , Female , Flow Cytometry , Humans , Immunophenotyping , Karyotype , Leukemia, T-Cell/diagnosis , Lymphoma, T-Cell/diagnosis , Male , Middle Aged , Young Adult
15.
Huan Jing Ke Xue ; 30(11): 3130-5, 2009 Nov.
Article in Chinese | MEDLINE | ID: mdl-20063718

ABSTRACT

By the soil respiration system of Li-6400, the characteristics of soil respiration with and without litter were investigated to explore the litter's contributions to soil respiration and its correlations with the input of litter and environmental factors under different land-use types in Sanjiang Plain. Results demonstrated that the average contribution of litter to soil respiration ranged from - 0.21 to 0.64 micromol/(m2 x s) in the growing season under the four land-use types. The contribution rate showed in the following order: wetland (14%) > artificial forest (12%) > soybean field (8%) > abandoned land (- 5%). As to abandoned land, the value was negative, and the litter inhibited soil respiration. The litter' s contributions to soil respiration may depend on the balance between the decomposition of litter and its shielding effects on soil respiration. There were highly significant correlations between litter's contributions to soil respiration and soil temperature at 10cm depth except for soybean field. Moreover, the influence of rainfall associated with the input of litter, which suggested that besides decomposition litter may take part in the ecological effect of climate changes in the future.


Subject(s)
Carbon Dioxide/analysis , Glycine max/growth & development , Soil/analysis , Trees/genetics , Wetlands , China , Environmental Monitoring , Plant Leaves/metabolism , Rain , Temperature
16.
Huan Jing Ke Xue ; 29(5): 1380-7, 2008 May.
Article in Chinese | MEDLINE | ID: mdl-18624211

ABSTRACT

The changes in microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) were examined in order to assess the effect of surface layer soil (0 - 10 cm) under different land-use types after freshwater marshes tillage in the Sanjiang Plain Northeast China. Land uses were Deyeuxia angustifolia freshwater marshes ((DAM), cultivated land (CL), recovery freshwater marsh (RFM), constructed woodland (CW). After DAM soil tillage, MBC, MBN, DOC and DON declined strongly in agricultural surface soil layer, decreased 63.8%-80.5% (MBC), 56.3%-67.1% (MBN), 43.1%-44.3% (DOC) and 25.2%-56.1% (DON) respectively. In contrast, these C, N fraction had significant recovered in RFM and CW surface soil, increased 36.1%-59.9% (MBC), 46.7%-65.9% (MBN), 67.0%-69.3% (DOC)and 81.2%-88.3% (DON) respectively. Cultivation and land-use affected soil MBC, MBN, DOC and DON intensely. Therefore these labile C, N fractions have the significant relative under different land-use types. However DOC was more obvious controlled than DON by the land-use types. The relative between DOC and MBC, MBN have much difference than DON, the main reason of this distinction is the diverse source in available carbon and nitrogen that taken by microbial property under different land uses.


Subject(s)
Carbon/analysis , Fresh Water/analysis , Nitrogen/analysis , Soil Microbiology , Wetlands , Biomass , Ecosystem , Fresh Water/microbiology , Poaceae/growth & development , Soil/analysis , Glycine max/growth & development , Trees/growth & development
17.
Ying Yong Sheng Tai Xue Bao ; 19(12): 2599-604, 2008 Dec.
Article in Chinese | MEDLINE | ID: mdl-19288710

ABSTRACT

Taking the typical marsh wetland plant Calamagrostis angustifolia in Sanjiang Plain of Northeast China as test material, a field control experiment was conducted to study its leaf morphological characters, chlorophyll content, and aboveground biomass under effects of different levels of exogenous nitrogen input in 2004-2007. Four nitrogen (N) fertilization treatments, i.e., 0 (CK), 6 g x m(-2) x a(-1) (N6), 12 g x m(-2) x a(-1) (N12) and 24 g x m(-2) x a(-1) (N24), were installed. The results showed that there were no significant differences in the leaf length and width among different N fertilization treatments, but the specific leaf area was the smallest (149.54 +/- 18.27 cm2 x g(-1)) under N12, which indicated that the leaves of C. angustifolia were thicker under this N treatment. The leaf chlorophyll content showed a unimodal distribution over the growth season, which increased with the amount of N input before the peak. The peak occurred earlier under N12 and N24 than under N6 and CK. After the peak, the chlorophyll content declined sharply under N24 but slowly under N6, indicating that moderate N input could delay leaf senescence. Continuous high N (N24) input might advance plant growth, while leaf senescence would occur earlier. By the end of growth season both in 2005 and in 2007, the aboveground biomass of C. angustifolia increased with increasing N input, but declined by 53.72% after 4 years continuous high N (N24) input (in 2007), compared with that after 2 years treatment (in 2005).


Subject(s)
Chlorophyll/analysis , Nitrogen/pharmacology , Plant Leaves/anatomy & histology , Poaceae/growth & development , Wetlands , Biomass , China , Plant Leaves/chemistry , Poaceae/drug effects , Poaceae/metabolism
18.
Huan Jing Ke Xue ; 29(12): 3525-30, 2008 Dec.
Article in Chinese | MEDLINE | ID: mdl-19256396

ABSTRACT

By laboratory incubation experiment, under aerobic and submerged soil moisture conditions, we investigated the mineralization of soil organic carbon (SOC) and contents of dissolved organic carbon (DOC) with different nitrogen inputs in a freshwater marsh soil. The results showed that under aerobic condition, there were no significant effects on the mineralization of SOC and contents of DOC as the net nitrogen input was 1 mg x g(-1) (N1), however, they were significantly higher than control and N1 treatments when nitrogen input increased to 2 and 5 mg x g(-1) (N2, N3), and the amount of DOC was respectively 187.22% and 203.25% higher than control (250.62 mg x kg(-1)). Under submerged condition, all N treatments restrained the mineralization of SOC, and the content of DOC was respectively 88.34% (N1), 82.69% (N2) and 80.04% (N3) lower than control (642.52 mg x kg(-1)). There were significant positive correlations between the contents of DOC and the amounts of cumulative C by mineralization (R2 was 0.939 and 0.843, respectively), which suggested that the changes of DOC affected by N input might be one of the important reasons that arose the differences of SOC mineralization. The results also indicate that as the waterlogged environment disappeared in wetland, the supply of exogenous nitrogen might bring large loss of SOC through enhancing the mineralization of SOC and leaching of DOC.


Subject(s)
Carbon/analysis , Nitrogen/chemistry , Organic Chemicals/analysis , Wetlands , Ammonia/chemistry , Biodegradation, Environmental , Carbon/chemistry , China , Ecosystem , Organic Chemicals/chemistry
19.
Zhonghua Fu Chan Ke Za Zhi ; 41(10): 656-9, 2006 Oct.
Article in Chinese | MEDLINE | ID: mdl-17199917

ABSTRACT

OBJECTIVE: To study the role of triptorelin in the treatment of patients with endometriosis, adenomyoma and fibromyoma and the effect of an extended-interval dosing regimen. METHODS: Seventy patients suffering from endometriosis, adenomyoma and fibromyoma were divided into two groups: extended-interval dosing (group E) and conventional dosing (group C). There were treated with injection of triptorelin 3.75 mg intramuscularly either every 6 weeks of totally four dose regimen (group E) or every 4 weeks of six dose regimen (group C). Comparison was made in improvement of symptoms, size of uterus and volume of tumor, as well as in serum levels of 17beta-estradiol, luteinizing hormone, and follicle-stimulating hormone. RESULTS: In each group, symptoms and tumor growth significantly improved after treatment (P < 0.05). For the patients of both groups E and C, the levels of gonadotropins and gonadal steroids were obviously reduced throughout the treatment period and up to 8 - 10 weeks after the injection of the last dose (P < 0.05). The hormonal profile of group E was similar to group C (P > 0.05). CONCLUSIONS: Gonadotropin-releasing hormone agonist is efficacious in the treatment of endometriosis and adenomyoma through reducing the serum levels of follicle-stimulating hormone, luteinizing hormone and 17beta-estradiol. The curative effect is satisfactory in most patients receiving an extended interval dosing regimen. To reduce the cost of treatment, the extended-interval dosing regimen of triptorelin should be adopted in well-equipped hospitals.


Subject(s)
Adenomyoma/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Endometriosis/drug therapy , Triptorelin Pamoate/therapeutic use , Uterine Neoplasms/drug therapy , Adult , Drug Administration Schedule , Dysmenorrhea/drug therapy , Female , Humans , Treatment Outcome
20.
Ai Zheng ; 24(10): 1196-200, 2005 Oct.
Article in Chinese | MEDLINE | ID: mdl-16219132

ABSTRACT

BACKGROUND & OBJECTIVE: The presence of Coxsackie and adenovirus receptor (CAR) on target cell surface is required for efficient adenovirus transfection; lack or down-regulated expression of CAR on cancer cells is the main cause of inefficiency of adenovirus-based gene therapy. This study was to evaluate enhancive effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on the transfection efficiency of adenovirus in ovarian carcinoma cell line A2780, and explore its possible application to adenovirus-based gene therapy. METHODS: mRNA and protein levels of CAR on A2780 cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot before and after treatment of TSA. Transfection efficiency of adenovirus was valued by flow cytometry (FCM). In vitro antitumor effect of adenovirus/thymidine kinase (ADV/TK) was detected by MTT assay. RESULTS: After treatment of TSA, mRNA and protein levels of CAR on A2780 cells were obviously increased. Transfection rates of adenovirus were (1.24+/-0.14)% in untreated group, (7.58+/-0.32)% in 5 nmol/L of TSA treated group, and (7.94+/-0.28)% in 100 nmol/L of TSA treated groups. In vitro antitumor effect of ADV/TK was 4-10 folds in TSA (5 or 100 nmol/L) treated groups compared with that in untreated group. CONCLUSION: TSA could enhance transfection efficiency of adenovirus in ovarian carcinoma cells, and may be useful in gene therapy for ovarian carcinoma.


Subject(s)
Adenoviridae/genetics , Histone Deacetylase Inhibitors , Hydroxamic Acids/pharmacology , Ovarian Neoplasms/pathology , Receptors, Virus/biosynthesis , Adenoviridae/physiology , Cell Line, Tumor , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Female , Humans , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/virology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Virus/genetics , Thymidine Kinase/pharmacology , Transfection
SELECTION OF CITATIONS
SEARCH DETAIL
...