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1.
Br J Haematol ; 204(6): 2351-2364, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38613241

RESUMEN

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.


Asunto(s)
Antígenos CD7 , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Inducción de Remisión , Humanos , Masculino , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto , Adolescente , Persona de Mediana Edad , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Adulto Joven , Niño , Recurrencia , Trasplante Homólogo , Receptores Quiméricos de Antígenos/uso terapéutico , Resultado del Tratamiento , Preescolar , Tasa de Supervivencia
2.
Ann Hematol ; 100(6): 1579-1591, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33236196

RESUMEN

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.


Asunto(s)
Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Hermanos , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
3.
Ann Hematol ; 99(12): 2911-2925, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33000361

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Donadores Vivos , Hermanos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/tendencias , Prueba de Histocompatibilidad/métodos , Prueba de Histocompatibilidad/tendencias , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/tendencias , Trasplante Haploidéntico/tendencias , Resultado del Tratamiento , Adulto Joven
4.
Zhonghua Nan Ke Xue ; 26(1): 3-16, 2020 Jan.
Artículo en Zh | MEDLINE | ID: mdl-33345471

RESUMEN

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.


Asunto(s)
Investigación Biomédica/tendencias , Salud Reproductiva , China , Fundaciones , Humanos , Masculino
5.
Biol Blood Marrow Transplant ; 24(9): 1881-1887, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29772350

RESUMEN

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.


Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anemia Aplásica/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
6.
Front Immunol ; 14: 1191382, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37469510

RESUMEN

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.


Asunto(s)
Linfoma de Burkitt , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Enfermedad Aguda , Neoplasia Residual
7.
Ecotoxicology ; 21(8): 2297-305, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22975893

RESUMEN

Glyphosate (GPS) is a wildly-used pesticide throughout the world. It affects metal behaviors in soil-water system as its functional groups such as amine, carboxylate and phosphonate can react with metal ions to form metal complexes. The reaction will result in the decreasing of heavy metal bioavailability. A laboratory experiment was conducted to investigate the interactions between GPS and copper (Cu) on the acute toxicity of soil invertebrate earthworm (Eisenia fetida), which was exposed to aqueous solutions for 48 h with different mixing concentrations of Cu and GPS (technical-grade Gly acid). The mortality rates, Cu uptake by earthworm, and some biomarkers such as superoxide dismutase (SOD) activity, glutathione (GSH) content, and acetylcholinesterase (AchE) activity were measured. The mortality rates and whole-worm metal burdens increased significantly with the increasing Cu concentration in solution. However, toxicity of GPS to earthworms was not observed in this study. Furthermore, the presence of GPS could significantly reduce the acute toxicity of Cu to earthworms. The mortality rates decreased sharply and the uptake of Cu was nearly halted in the presence of GPS. In addition, the SOD activity, GSH content, and AchE activity almost declined to the levels of the control. These results demonstrate that GPS could control the toxicity as well as the bioavailability of heavy metals in soil solutions where both GPS and heavy metals often coexist.


Asunto(s)
Cobre/toxicidad , Glicina/análogos & derivados , Oligoquetos/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Animales , Disponibilidad Biológica , Cobre/farmacocinética , Glicina/farmacocinética , Glicina/toxicidad , Oligoquetos/metabolismo , Contaminantes del Suelo/farmacocinética , Espectrofotometría , Espectrofotometría Atómica , Glifosato
8.
Leuk Lymphoma ; 63(5): 1211-1219, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34913818

RESUMEN

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.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hemoglobinuria Paroxística , Pancitopenia , Trastornos de Fallo de la Médula Ósea , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/terapia , Humanos , Pancitopenia/etiología , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Donante no Emparentado
9.
Leuk Lymphoma ; 63(13): 3092-3099, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36067510

RESUMEN

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.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante , Enfermedad Aguda , Trastornos Mieloproliferativos/patología , Células Dendríticas/patología
10.
Leuk Lymphoma ; 63(14): 3307-3316, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36067518

RESUMEN

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.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Donante no Emparentado , Estudios Retrospectivos , Donantes de Sangre , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Recurrencia , Acondicionamiento Pretrasplante
11.
Front Immunol ; 13: 1066748, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36685540

RESUMEN

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.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Recurrencia Local de Neoplasia/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neoplasias Hematológicas/terapia , Enfermedad Crónica
12.
Hematology ; 26(1): 134-143, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33491597

RESUMEN

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.


Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Donante no Emparentado , Adulto Joven
13.
Front Immunol ; 12: 605766, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34025637

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Antígenos CD19 , Antígenos de Neoplasias , Niño , Terapia Combinada , Resistencia a Antineoplásicos , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Pronóstico , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Recurrencia , Retratamiento , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
14.
J Hazard Mater ; 151(1): 179-84, 2008 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-17604908

RESUMEN

Cosorption of metals with herbicides on minerals affects their mobility and their environmental effect. Batch experiments were conducted to evaluate the interaction between Zn and glyphosate [N-(phosphonomethyl)glycine (GPS; H3L)] with regard to the effect of GPS on Zn adsorption on goethite. The herbicide GPS markedly affected Zn adsorption on goethite when they coexisted in a goethite suspension. When solution pH was not intentionally adjusted, addition of GPS decreased Zn adsorption on goethite, since the equilibrium solution pH was significantly decreased in the presence of GPS and correspondingly the negative surface charges of goethite decreased. Zinc adsorption on goethite in the presence and absence of GPS at different pH of the equilibrium solution was studied in order to know if pH was the only variable for Zn adsorption with coexisting GPS. At lower pH (pH<5), the presence of GPS increased the adsorption of Zn, because Zn adsorbed on the sites of goethite via GPS bridge. However, at higher pH (pH>5), the presence of GPS decreased the adsorption of Zn on goethite, because GPS reacted with solution Zn to form water-soluble complexes that had lower affinity to the goethite surface in comparison with Zn itself. Zeta potential of goethite significantly decreased after adsorption of GPS, suggesting a chemical bond occurred between GPS and the mineral. FTIRs also show that GPS adsorbs on goethite by coordinating through caboxylate group.


Asunto(s)
Glicina/análogos & derivados , Herbicidas/química , Compuestos de Hierro/química , Zinc/química , Adsorción , Glicina/química , Minerales , Espectroscopía Infrarroja por Transformada de Fourier , Glifosato
17.
Environ Sci Pollut Res Int ; 25(1): 73-80, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27844320

RESUMEN

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.


Asunto(s)
Cobre/análisis , Durapatita/química , Nanopartículas/química , Contaminantes del Suelo/análisis , Zinc/análisis , Disponibilidad Biológica , Biomasa , China , Lolium/química , Lolium/crecimiento & desarrollo , Modelos Teóricos , Suelo/química
18.
J Hazard Mater ; 137(1): 76-82, 2006 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-16600484

RESUMEN

Agricultural application of large amounts of glyphosate [N-(phosphonomethyl)-glycine] may affect soil metal behaviors to some extend, because glyphosate can react with many kinds of metals to form metal complexes. Cosorption of Zn and glyphosate on a Red soil (RS, Udic Ferrosols) and a Wushan soil (WS, Anthrosol) was studied. In comparison with the WS, the RS has less adsorption capacity for Zn and higher for glyphosate. The presence of glyphosate decreased Zn adsorption on the two soils, which are resulted from the decreased equilibrium solution pH caused by the added glyphosate, and also the formation of water-soluble complexes of glyphosate with solution Zn(2+) that had lower affinity to soil surface in comparison with Zn(2+) itself. Such effect is more significant on the RS than on the WS, mainly because of the less adsorption quantity of Zn on the former one. On the contrary, the presence of Zn increased the adsorption quantities of glyphosate on the RS and WS, which is resulted from the decreasing pH value of the equilibrium solution caused by Zn(2+) exchange with H(+) ions of soil surface. Such results suggest that glyphosate in field may increase the mobility and bioavailability of Zn and correspondingly increase its environmental risk.


Asunto(s)
Glicina/análogos & derivados , Sustancias Peligrosas , Contaminantes del Suelo , Suelo , Zinc/análisis , Adsorción , Glicina/análisis , Herbicidas , Concentración de Iones de Hidrógeno , Protones , Zinc/química , Compuestos de Zinc , Glifosato
19.
J Environ Sci (China) ; 17(5): 711-5, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16312989

RESUMEN

Glyphosate (GPS) is a non-selective, post-mergence herbicide that is widely used throughout the world. Due to the similar molecular structures of glyphosate and phosphate, adsorption of glyphosate on soil is easily affected by coexisting phosphate, especially when phosphate is applied at a significant rate in farmland. This paper studied the effects of phosphate on the adsorption of glyphosate on three different types of Chinese soils including two variable charge soils and one permanent charge soil. The results indicated that Freundlich equations used to simulate glyphosate adsorption isotherms gave high correlation coefficients (0.990-0.998) with K values of 2751, 2451 and 166 for the zhuanhong soil(ZH soil, Laterite), red soil(RS, Udic Ferrisol) and Wushan paddy soil (WS soil, Anthrosol), respectively. The more the soil iron and aluminum oxides and clay contained, the more glyphosate adsorbed. The presence of phosphate significantly decreased the adsorption of glyphosate to the soils by competing with glyphosate for adsorption sites of soils. Meanwhile, the effects of phosphate on adsorption of glyphosate on the two variable charge soils were more significant than that on the permanent charge soil. When phosphate and glyphosate were added in the soils in different orders, the adsorption quantities of glyphosate on the soils were different, which followed GPS-soil > GPS-P-soil = GPS-soil-P > P-soil-GPS, meaning a complex interaction occurred among glyphosate, phosphate and the soils.


Asunto(s)
Glicina/análogos & derivados , Herbicidas/química , Fosfatos/química , Suelo/análisis , Adsorción , China , Cromatografía Líquida de Alta Presión , Glicina/química , Concentración de Iones de Hidrógeno , Glifosato
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