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1.
Br J Haematol ; 204(6): 2351-2364, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613241

RESUMO

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.


Assuntos
Antígenos CD7 , Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Indução de Remissão , Humanos , Masculino , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Adolescente , Pessoa de Meia-Idade , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Adulto Jovem , Criança , Recidiva , Transplante Homólogo , Receptores de Antígenos Quiméricos/uso terapêutico , Resultado do Tratamento , Pré-Escolar , Taxa de Sobrevida
2.
Front Immunol ; 14: 1191382, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469510

RESUMO

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.


Assuntos
Linfoma de Burkitt , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Doença Aguda , Neoplasia Residual
3.
Leuk Lymphoma ; 63(13): 3092-3099, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36067510

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic malignancy characterized by poor prognosis even following an allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 15 patients diagnosed with BPDCN who underwent an allo-HSCT with myeloablative conditioning (MAC) at our center. The male to female ratio was 11:4. The median age of 36 (range: 6-70) years, all patients initially presented with extramedullary lesions (13 with cutaneous lesions, 1 in the breast and 1 in the lymph nodes) and involved the bone marrow, two cases were diagnosed as central nervous system leukemia (CNSL). Nine patients were in CR1 and six patients were in CR2 status prior to HSCT. All patients received the MAC regimen and an unmanipulated graft. All patients successfully engraftment and achieved full donor chimerism. One patient developed poor graft function, three patients developed aGVHD (Grade I, II, and IV), and seven patients developed cGVHD (mild in 6; moderate in 1). The median follow-up time for survival was 34 (range: 6-64) months. The primary endpoint, overall leukemia-free survival (LFS) rate and overall survival rate was 73.3 ± 10.5%. Allo-HSCT with MAC is a valid option for BPDCN patients in complete remission.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante , Doença Aguda , Transtornos Mieloproliferativos/patologia , Células Dendríticas/patologia
4.
Leuk Lymphoma ; 63(14): 3307-3316, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36067518

RESUMO

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.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Doadores não Relacionados , Estudos Retrospectivos , Doadores de Sangue , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva , Condicionamento Pré-Transplante
5.
Leuk Lymphoma ; 63(5): 1211-1219, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34913818

RESUMO

We analyzed the outcomes of 32 patients with paroxysmal nocturnal hemoglobinuria (PNH) who underwent either a haploidentical donor (HID) or a matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). Seventeen patients received an HSCT from an HID and 15 patients received an HSCT from an MUD. The median follow-up time of the surviving patients was 36 months (range: 12-96 months). No significant differences were observed in the 3-year overall survival (OS) between the HID and MUD cohorts (74.1%±11.4% vs. 93.3%±6.4%, respectively, p=.222) or in the 3-year failure-free survival (68.8%±11.8% vs. 86.7%±8.8%, respectively, p=.307). Treatment-related mortality occurred in five patients. A univariate analysis of risk factors revealed platelet engraftment failure negatively impacted OS and FFS. We conclude that HID and MUD-HSCT are feasible and can be effective options for those PNH patients with concomitant bone marrow failure, recurrent life-threatening thrombosis, and uncontrollable hemolysis.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Pancitopenia , Transtornos da Insuficiência da Medula Óssea , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/terapia , Humanos , Pancitopenia/etiologia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Doadores não Relacionados
6.
Front Immunol ; 13: 1066748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36685540

RESUMO

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.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hematológicas/terapia , Doença Crônica
7.
Front Immunol ; 12: 605766, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025637

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Antígenos CD19 , Antígenos de Neoplasias , Criança , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Prognóstico , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Recidiva , Retratamento , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
8.
Hematology ; 26(1): 134-143, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33491597

RESUMO

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.


Assuntos
Síndrome Congênita de Insuficiência da Medula Óssea/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Doadores não Relacionados , Adulto Jovem
9.
Ann Hematol ; 100(6): 1579-1591, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33236196

RESUMO

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.


Assuntos
Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Irmãos , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
10.
Zhonghua Nan Ke Xue ; 26(1): 3-16, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33345471

RESUMO

Reproductive health is a key aim of the population health strategy, and male reproductive health constitutes an important part of reproductive health. This article systematically analyzes the applications to and grants from the National Natural Science Foundation of China (NSFC) and some related scientific problems in the field of male reproductive health in the past 30 years. It also discusses the development of the basic researches on male reproductive health in China and the facilitating role of NSFC in this field.


Assuntos
Pesquisa Biomédica/tendências , Saúde Reprodutiva , China , Fundações , Humanos , Masculino
11.
Ann Hematol ; 99(12): 2911-2925, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33000361

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Doadores Vivos , Irmãos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , Teste de Histocompatibilidade/métodos , Teste de Histocompatibilidade/tendências , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/tendências , Transplante Haploidêntico/tendências , Resultado do Tratamento , Adulto Jovem
13.
Biol Blood Marrow Transplant ; 24(9): 1881-1887, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29772350

RESUMO

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.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Anemia Aplástica/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
14.
Environ Sci Pollut Res Int ; 25(1): 73-80, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27844320

RESUMO

Phosphate compounds and related materials are effective amendments for immobilization of heavy metals in contaminated soils. A greenhouse pot experiment with ryegrass (Lolium perenne) as the test plant was conducted to explore the impact of nanoparticle hydroxyapatite (HAP) on the immobilization and bioavailability of Cu and Zn in a heavy metal-polluted soil. The addition of nanoparticle HAP significantly decreased the uptake of Cu and Zn by ryegrass. As a result, the biomass of ryegrass increased as the rate of nanoparticle HAP increased. The toxicity characteristic leaching procedure (TCLP) and physiologically based extraction test (PBET) results of the treatments showed that the leachable and bioaccessible concentrations of Cu and Zn were significantly reduced after the soil stabilized with nanoparticle HAP. The XRD pattern of nanoparticle HAP was not changed by the presence of Cu and Zn, which suggests that Cu and Zn were immobilized by the formation of solid amorphous phosphate. Nanoparticle HAP was an effective material to immobilize heavy metals in contaminated soils.


Assuntos
Cobre/análise , Durapatita/química , Nanopartículas/química , Poluentes do Solo/análise , Zinco/análise , Disponibilidade Biológica , Biomassa , China , Lolium/química , Lolium/crescimento & desenvolvimento , Modelos Teóricos , Solo/química
15.
J Dig Dis ; 16(8): 421-30, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26215325

RESUMO

Up to 100 trillion bacteria are harbored in the human intestine with a mutualistic and interdependent relationship with the host during a long period of co-evolution. The so-called intestinal microbiota (IM) fulfill important metabolic tasks and the impaired stability may lead to IM-related diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), metabolic syndrome (MS), liver diseases, and so on. Here, we review the past and development of IM research in China, including the achievements that Chinese researchers have made both in basic and clinical scientific field. Moreover, we evaluate the contributions of the National Natural Science Foundation of China (NSFC), the 973 National Basic Research Program of China (973 Program), the 863 National High Technology Research and Development Program of China (863 Program), and funds from the public health industry in the field of IM research.


Assuntos
Microbioma Gastrointestinal , Pesquisa Biomédica/economia , Pesquisa Biomédica/tendências , China , Neoplasias Colorretais/microbiologia , Transplante de Microbiota Fecal , Gastroenteropatias/terapia , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Hepatopatias/microbiologia , Síndrome Metabólica/microbiologia , Apoio à Pesquisa como Assunto/estatística & dados numéricos , Apoio à Pesquisa como Assunto/tendências
16.
Environ Toxicol Chem ; 33(10): 2351-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25043609

RESUMO

The acute and subacute toxicities of cadmium (Cd) to earthworm Eisenia fetida in the presence and absence of glyphosate were studied. Although Cd is highly toxic to E. fetida, the presence of glyphosate markedly reduced the acute toxicity of Cd to earthworm; both the mortality rate of the earthworms and the accumulation of Cd decreased with the increase of the glyphosate/Cd molar ratio. The subcellular distribution of Cd in E. fetida tissues showed that internal Cd was dominant in the intact cells fraction and the heat-stable proteins fraction. The presence of glyphosate reduced the concentration of Cd in all fractions, especially the intact cells. During a longer period of exposure, the weight loss of earthworm and the total Cd absorption was alleviated by glyphosate. Thus, the herbicide glyphosate can reduce the toxicity and bioavailability of Cd in the soil ecosystems at both short- and long-term exposures.


Assuntos
Cádmio/toxicidade , Glicina/análogos & derivados , Herbicidas/metabolismo , Oligoquetos/efeitos dos fármacos , Oligoquetos/fisiologia , Poluentes do Solo/toxicidade , Animais , Disponibilidade Biológica , Cádmio/análise , Cádmio/metabolismo , Glicina/análise , Glicina/metabolismo , Herbicidas/análise , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Glifosato
19.
Environ Pollut ; 180: 71-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23733011

RESUMO

Glyphosate (GPS) and copper (Cu) are common pollutants in soils, and commonly co-exist. Due to the chemical structure of GPS, it can form complexes of heavy metals and interface their bioavailability in soil environment. In order to explore the interactions between GPS and Cu, subacute toxicity tests of Cu and GPS on soil invertebrate earthworms (Eisenia fetida) were conducted. The relative weight loss and whole-worm metal burdens increased significantly with the increasing exposure concentration of Cu, while the toxicity of GPS was insignificant. The joint toxicity data showed that the relative weight loss and the uptake of Cu, as well as the superoxide dismutase, catalase and malondialdehyde activities, were significantly alleviated in the present of GPS, which indicated that GPS could reduce the toxicity and bioavailability of Cu in the soil because of its strong chelating effects.


Assuntos
Cobre/toxicidade , Glicina/análogos & derivados , Poluentes do Solo/toxicidade , Animais , Glicina/toxicidade , Oligoquetos , Glifosato
20.
Chemosphere ; 92(8): 925-32, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23541148

RESUMO

Tetracyclines are widely-used antibiotics in the world. Due to their poor absorption by human beings, or poultry and livestocks, most of them are excreted into the environment, causing growing concern about their potential impact, while photodegradation has been found to dominate their sequestration and bioavailability. Coupling with high-performance liquid chromatography-mass spectroscopy (HPLC-MS), gas chromatography-mass spectroscopy (GC-MS) and electron spin resonance (ESR), the mechanism of photocatalytic degradation of TC in aqueous solution by nanosized TiO2 (P25) under UV irradiation was investigated. The photocatalysis eliminated 95% of TC and 60% of total organic carbon (TOC) after 60 min irradiation, and NH4(+) ion was found to be one of the end-products. Bioluminescence assay showed that the toxicity of TC solution reached the maximum after 20 min irradiation and then gradually decreased. The degradation of TC included electron transfer, hydroxylation, open-ring reactions and cleavage of the central carbon. A possible photocatalytic degradation pathway of TC was proposed on the basis of the identified intermediates. Overall, the TiO2 photocatalysis was found to be a promising process for removing TC and its intermediates.


Assuntos
Antibacterianos/química , Nanopartículas/química , Tetraciclina/química , Titânio/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Compostos de Amônio/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância de Spin Eletrônica , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Tamanho da Partícula , Fotólise , Raios Ultravioleta
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