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1.
Br J Haematol ; 205(2): 510-516, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38671583

RESUMO

There is an urgent need for an oral, efficient and safe regimen for high-risk APL under the pandemic of COVID-19. We retrospectively analysed 60 high-risk APL patients. For induction therapy (IT), in addition to all-trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650-1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8-44) versus 35 days (32-42; p = 0.75) and 3 months (0.8-3.5) versus 3.3 months (2.4-3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2-year estimated overall survival and event-free survival were 100% versus 94.7% (p = 0.37) and 90.9% versus 89.5% (p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high-risk APL.


Assuntos
Etoposídeo , Quimioterapia de Indução , Leucemia Promielocítica Aguda , Humanos , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Administração Oral , Estudos Retrospectivos , Quimioterapia de Indução/métodos , Infusões Intravenosas , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , COVID-19 , Tretinoína/administração & dosagem , Tretinoína/uso terapêutico , SARS-CoV-2 , Indução de Remissão , Arsênio/administração & dosagem , Idoso
2.
Hematol Oncol ; 42(2): e3256, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367260

RESUMO

This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1mut ) and 144 AML patients with wild-type RUNX1(AML-RUNX1wt ) were selected using the case-pair method(1:4). Compared to AML-RUNX1wt , AML-RUNX1mut showed higher frequency of ASXL1 (p < 0.001), SRSF2 (p < 0.001), BCORL1 (p < 0.001), RAS (p = 0.010) mutations, and absent NPM1 mutations (p = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1mut and AML-RUNX1wt were 73.1% versus 68.0% (p = 0.64) and 80.7% versus 71.6% (p = 0.37), respectively. AML-RUNX1mut receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; p = 0.006). Multivariate analysis showed that EZH2 mutation (p = 0.003), white blood cell (WBC) ≥30 × 109 /L (p = 0.036) and age ≥60 years (p = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1mut ; WBC ≥30 × 109 /L (p = 0.013) and DNMT3A mutation (p = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1mut . In conclusion, AML-RUNX1mut showed unique clinical characteristics, but the survival between AML-RUNX1mut and AML-RUNX1wt were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut . Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut .


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Humanos , Pessoa de Meia-Idade , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Nucleofosmina , Prognóstico , Estudos Retrospectivos
3.
Br J Haematol ; 200(6): 759-768, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36464324

RESUMO

Prolonged isolated thrombocytopenia (PT) is a life-threatening comorbidity associated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). Our previous study indicated that dysfunctional bone marrow mesenchymal stromal cells (BM MSCs) played a role in PT pathogenesis and that reactive oxygen species (ROS) accumulation was related to BM MSC senescence and apoptosis. However, the mechanism of the increase in ROS levels in the BM MSCs of PT patients is unknown. In the current case-control study, we investigated whether nuclear factor erythroid 2-related factor 2 (NRF2), which is a central regulator of the cellular anti-oxidant response that can clear ROS in human BM MSCs, was associated with PT after allo-HSCT. We evaluated whether an NRF2 agonist (tert-butylhydroquinone, TBHQ) could enhance BM MSCs from PT patients in vitro. We found that BM MSCs from PT patients exhibited increased ROS levels and reduced NRF2 expression. Multivariate analysis showed that low NRF2 expression was an independent risk factor for primary PT [p = 0.032, Odds ratio (OR) 0.868, 95% confidence interval (CI) 0.764-0.988]. In-vitro treatment with TBHQ improved the quantity and function of BM MSCs from PT patients by downregulating ROS levels and rescued the impaired BM MSC support of megakaryocytopoiesis. In conclusion, these results suggested that NRF2 downregulation in human BM MSCs might be involved in the pathogenesis of PT after allo-HSCT and that BM MSC impairment could be improved by NRF2 agonist in vitro. Although further validation is needed, our data indicate that NRF2 agonists might be a potential therapeutic approach for PT patients after allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Trombocitopenia , Humanos , Medula Óssea/patologia , Estudos de Casos e Controles , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células da Medula Óssea/patologia , Trombocitopenia/etiologia , Células-Tronco Mesenquimais/metabolismo , Transplante de Células-Tronco Mesenquimais/efeitos adversos
4.
BMC Pregnancy Childbirth ; 23(1): 604, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612626

RESUMO

BACKGROUD: To investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. METHODS: A total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2). RESULTS: There were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001). CONCLUSION: LH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.


Assuntos
Hormônio Luteinizante , Oócitos , Humanos , Estudos Retrospectivos , Transferência Embrionária , Antagonistas de Hormônios/uso terapêutico , Hormônio Liberador de Gonadotropina
5.
Br J Haematol ; 196(3): 735-742, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34741461

RESUMO

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.


Assuntos
Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Algoritmos , Anemia Aplástica/diagnóstico , Anemia Aplástica/epidemiologia , Causas de Morte , Tomada de Decisão Clínica , Estudos de Coortes , Árvores de Decisões , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Mortalidade , Prognóstico , Índice de Gravidade de Doença , Transplante Haploidêntico , Resultado do Tratamento
6.
Br J Haematol ; 195(5): 722-730, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34405393

RESUMO

Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.


Assuntos
Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Quimioterapia de Indução , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
7.
Clin Transplant ; 35(2): e14160, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33222318

RESUMO

OBJECTIVES: The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. METHODS: A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. RESULTS: Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort. CONCLUSIONS: Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Quimerismo , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Fatores de Proteção , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento
8.
Biol Blood Marrow Transplant ; 26(2): 351-357, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31704470

RESUMO

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplant (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2 to 9). The day 28 overall response rate was 85%, with complete response in 74% of patients, partial response in 11% of patients, and no response in 15% of patients. The day 28 overall response rates were 94.6% in skin SR aGVHD, 81.6% in gut SR aGVHD, and 66.7% in liver SR aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), cytomegalovirus viremia (53%), Epstein-Barr virus viremia (11%), human herpesvirus-6 viremia (7%), and herpes simplex virus viremia (1%). The 3-year overall survival, disease-free survival, nonrelapse mortality, and relapse rates between responders and nonresponders were 81.3% versus 46.7% (P < .001), 79.0% versus 46.7% (P = .001), 6.1% versus 33.3% (P < .001), and 14.9% versus 20.0% (P = .46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR aGVHD after haplo-HSCT, particularly for skin SR aGVHD.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Adulto , Basiliximab , Criança , Doença Enxerto-Hospedeiro/tratamento farmacológico , Herpesvirus Humano 4 , Humanos , Estudos Retrospectivos , Esteroides
9.
Biol Blood Marrow Transplant ; 26(8): 1452-1458, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32311479

RESUMO

The aim of this study was to evaluate the incidence, risk factors, and outcomes of primary prolonged isolated thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplant (haplo-HSCT). We retrospectively analyzed patients who received haplo-HSCT for various hematologic malignancies at Peking University Institute of Hematology between January 2015 and December 2016. Of the 918 patients, 93 (10.1%) developed primary PT. We designed a propensity score method-based study. For each primary PT patient control subjects (1:3) were selected using a propensity score-matching method. A total of 372 recipients were enrolled in the study: 93 in the PT group and 279 in the control group. Multivariate analysis showed that age older than 25 years (P = .002), median mononuclear cells (P = .000), median CD34+ counts (P = .003), history of grades II to IV acute graft-versus-host disease (GVHD; P = .000), and Epstein-Barr virus (EBV) infection after haplo-HSCT (P = .016) were independent risk factors for primary PT. Primary PT was significantly associated with higher transplant-related mortality (TRM; P < .001), inferior overall survival (P = .001), and disease-free survival (P = .005). In conclusion, the incidence of primary PT after haplo-HSCT was 10.1%. Primary PT was associated with poorer survival and higher TRM along with older age, grades II to IV acute GVHD, and EBV infection after haplo-HSCT.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Trombocitopenia , Adulto , Idoso , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4 , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia
10.
Biol Blood Marrow Transplant ; 26(9): 1655-1662, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32504861

RESUMO

The specific description, risk factors, and outcomes of chronic graft-versus-host disease (cGVHD) in pediatric patients with hematologic malignancies after T cell-replete (TCR) myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with antithymocyte globulin (ATG)/granulocyte colony-stimulating factor (G-CSF) have not been previously well described. We retrospectively analyzed the incidence, risk factors, and outcomes of cGVHD documented according to the 2014 National Institutes of Health consensus criteria (NIH-CC) in 292 consecutive pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF between January 2015 and December 2017. A total of 170 patients experienced cGVHD. The 3-year cumulative incidence of total cGVHD and mild, moderate, and severe cGVHD was 57.9%, 27.5%, 18.8%, and 11.9%, respectively. Multivariate analysis showed that acute GVHD (aGVHD) grade II-IV (hazard ratio, 1.578; P = .002) was an independent risk factor for cGVHD. Compared to patients without cGVHD, patients with cGVHD demonstrated a lower 3-year relapse (17.6% versus 27.2%; P = .009), a similar 3-year nonrelapse mortality (NRM) (5.9% versus 5.4%; P = .79), and better 3-year disease-free survival (DFS) (77.8% versus 66.9%; P = .007) and overall survival (OS) (81.3% versus 68.6%; P = .001), particularly those with mild or moderate cGVHD; however, no significant impact of severe cGVHD on relapse, NRM, DFS, or OS was seen. In conclusion, the incidence of severe cGVHD in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF was acceptable. Previous aGVHD grade II-IV was a risk factor for the occurrence of cGVHD. Only mild or moderate cGVHD was associated with a lower risk of relapse, translating into improved DFS and OS in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Soro Antilinfocitário , Criança , Doença Enxerto-Hospedeiro/etiologia , Fator Estimulador de Colônias de Granulócitos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Linfócitos T , Condicionamento Pré-Transplante
11.
Pediatr Transplant ; 24(7): e13793, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32741088

RESUMO

The specific description, risk factors, and outcomes of aGVHD in pediatric haplo-HSCT using TCR protocols without PT-Cy have not been well described previously. We evaluated the incidence, risk factors, and outcomes of aGVHD in 350 consecutive pediatric patients receiving TCR haplo-HSCT without PT-Cy according to the Glucksberg and NIH aGVHD classifications between January 2015 and December 2017 at Peking University Institute of Hematology. The cumulative incidences of grade I, II, III, and IV aGVHD were 28%, 29.7%, 8.3%, and 5.1%, respectively. The type of aGVHD onset was classic in 243 patients (97.2%), and persistent/recurrent/late-onset aGVHD was in seven patients (2.8%). None of the considered variables significantly influenced the incidence of grade III-IV aGVHD. The 3-year OS, DFS, cumulative incidence of NRM, and relapse in malignant disease between severe aGVHD (III-IV) group and grade 0-II aGVHD group were 61.5% vs 77.2% (P = .027), 58.6% vs 75.1% (P = .014), 19.8% vs 5.3% (P = .002), and 21.6% vs 19.6% (P = .59), respectively; in non-malignant diseases, the 3-year OS, DFS, and NRM were 81.8% vs 97.4% (P = .05), 81.8% vs 97.4% (P = .05), and 18.2% vs 2.6% (P = .05), respectively. Under the protocol of pediatric TCR haplo-HSCT without PT-Cy, the persistent/recurrent/late-onset aGVHD was rare, and the incidence of severe aGVHD was acceptable and significantly contributed to NRM and lower survival in both malignant disease and non-malignant diseases.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunidade Celular , Linfócitos T/microbiologia , Adolescente , Adulto , Biópsia , Criança , China/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Condicionamento Pré-Transplante , Adulto Jovem
12.
Biol Blood Marrow Transplant ; 25(3): 529-537, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30481596

RESUMO

This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n = 83, group A) or high risk; patients at high risk were randomly assigned to receive (n = 72, group B) or not receive (n = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100days after transplantation (hazard ratio, 1.547; P = .015) and platelet recovery (hazard ratio, 1.456; P = .037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.).


Assuntos
Intervalo Livre de Doença , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Metilprednisolona/uso terapêutico , Pré-Medicação/métodos , Transplante Haploidêntico , Adulto , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/etiologia , Seguimentos , Glucocorticoides/farmacologia , Humanos , Infecções/induzido quimicamente , Infecções/etiologia , Masculino , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Transplante Haploidêntico/métodos , Transplante Haploidêntico/mortalidade , Transplante Homólogo
13.
Br J Haematol ; 184(5): 788-796, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30426480

RESUMO

Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6-55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0-5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Anticorpos Anti-Hepatite/sangue , Hepatite E , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Hepatite E/sangue , Hepatite E/genética , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
15.
J Opt Soc Am A Opt Image Sci Vis ; 36(7): 1146-1151, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503952

RESUMO

By using the technique of integration within ordered product of operators, we put forward the combinatorial optical complex wavelet-fractional Fourier transform in the context of quantum optics. The unitary operator for this new transform is found and its normally ordered form is deduced. We apply this new transform to the two-mode vacuum state and the two-mode number state and explain that it can be used to analyze and identify various quantum optical states.

16.
Biol Blood Marrow Transplant ; 24(10): 1981-1989, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29933074

RESUMO

Poor graft function (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by defective hematopoiesis. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis, but little is known about the role of MSCs in the pathogenesis of PGF. In the current prospective case-control study, we evaluated whether the number and function of bone marrow (BM) MSCs in PGF patients differed from those in good graft function (GGF) patients. We found that BM MSCs from PGF patients expanded more slowly and appeared flattened and larger, exhibiting more apoptosis and senescence than MSCs from GGF patients. Furthermore, increased intracellular reactive oxygen species, p-p53, and p21 (but not p38) levels were detected in MSCs from PGF patients. Moreover, the ability of MSCs to sustain hematopoiesis was significantly reduced in PGF patients, as evaluated by cell number, apoptosis, and the colony-forming unit-plating efficiency of CD34+ cells. In summary, the biologic characteristics of PGF MSCs are different from those of GGF MSCs, and the in vitro hematopoiesis-supporting ability of PGF MSCs is significantly lower. Although requiring further validation, our study indicates that reduced and dysfunctional BM MSCs may contribute to deficient hematopoiesis in PGF patients. Therefore, improvement of BM MSCs may represent a promising therapeutic approach for PGF patients after allo-HSCT.


Assuntos
Células da Medula Óssea/metabolismo , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais/metabolismo , Adolescente , Adulto , Aloenxertos , Células da Medula Óssea/patologia , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Br J Haematol ; 180(6): 863-878, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29392716

RESUMO

Prolonged isolated thrombocytopenia (PT) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies and in vitro experiments suggest that mesenchymal stem cells (MSCs) can, not only to support haematopoiesis, but also preferentially support megakaryocytopoiesis in bone marrow (BM). However, little is known about the quantity and function of BM MSCs in PT patients. In a case-control study, we found that BM MSCs from PT patients exhibited significantly reduced proliferative capacities, increased reactive oxygen species and senescence. Antioxidant (N-acetyl-L-cysteine, NAC) treatment in vitro not only quantitatively and functionally improved BM MSCs derived from PT patients through down-regulation of the p38 (also termed MAPK14) and p53 (also termed TP53) pathways but also partially rescued the impaired ability of BM MSCs to support megakaryocytopoiesis. Subsequently, a pilot study showed that the overall response of NAC treatment was obtained in 7 of the enrolled PT patients (N = 10) without significant side effects. Taken together, the results indicated that dysfunctional BM MSCs played a role in the pathogenesis of PT and the impaired BM MSCs could be improved by NAC in vitro. Although requiring further validation, our data indicate that NAC might be a potential therapeutic approach for PT patients after allo-HSCT.


Assuntos
Acetilcisteína/administração & dosagem , Células da Medula Óssea/metabolismo , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Células-Tronco Mesenquimais/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Trombocitopenia/tratamento farmacológico , Células da Medula Óssea/patologia , Estudos de Casos e Controles , Feminino , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Prospectivos , Trombocitopenia/etiologia , Trombocitopenia/metabolismo , Trombocitopenia/patologia
18.
Clin Transplant ; 32(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29090481

RESUMO

OBJECTIVES: Pulmonary infiltrates in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients are potentially life-threatening and require early diagnosis and treatment. We aimed to retrospectively explore the clinical efficacy of polymerase chain reaction (PCR) in conjunction with flexible bronchoscopy (FB) in allo-HSCT patients with pulmonary infiltrates. PATIENTS AND METHODS: We retrospectively reviewed all patients undergoing FB after allo-HSCT at the Peking University Institute of Hematology from January 2013 to December 2016. We used PCR to detect various viruses in FB specimens, particularly for 27 viruses. RESULTS: One hundred forty-nine diagnostic FBs were performed in 130 patients. The overall diagnostic yield was 58%. Eighty-nine percent of the patients with a positive FB result were diagnosed with a pulmonary infection. Viruses were the most common infectious diagnosis (70%), followed by fungi (48%), bacteria (38%), and Pneumocystis jirovecii (12%). Multivariate analyses showed that a chest computed tomography (CT) finding of diffuse pulmonary infiltrates (P = .012) and positive results in assisted microbiological and serological analyses (P = .000) predicted a positive FB result. FB results prompted a treatment modification in 61% of cases. CONCLUSIONS: FB in conjunction with PCR is efficient in the rapid diagnosis and management of pulmonary infiltrates in allo-HSCT patients.


Assuntos
Anti-Infecciosos/uso terapêutico , Broncoscopia/métodos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Reação em Cadeia da Polimerase/métodos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Infecções Respiratórias/etiologia , Estudos Retrospectivos , Adulto Jovem
19.
Lipids Health Dis ; 13: 124, 2014 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-25095788

RESUMO

BACKGROUND: Previous studies reported the relation between MTLRP genetic polymorphism and type 2 diabetes, however, the conclusion were conflicting. In the present study, we performed a meta-analysis to reveal this association. METHODS: Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model or fixed-effect model to pool the Odds ratio (OR) according to the test of heterogeneity. RESULTS: A total of nine case-control studies included 4460 type 2 diabetes patients and 4114 healthy control subjects were analyzed. We did not found association between the MTLRP polymorphism and type 2 diabetes risk in the overall population (CC vs CA + AA: OR = 1.02; 95% CI: 0.89-1.17, P = 0.77; A vs C: OR = 1.02; 95% CI: 0.84-0.96, P = 0.62). However, in subgroup analyses stratified by ethnicity, we found significant association of MTLRP polymorphism with type 2 diabetes in Caucasians (CC vs CA + AA: OR = 1.27; 95% CI: 1.02-1.57, P = 0.03; A vs C: OR = 0.74, 95% CI: 0.60-0.91, P = 0.005). CONCLUSION: The MTLRP polymorphism was associated with type 2 diabetes in Caucasians.


Assuntos
Diabetes Mellitus Tipo 2/genética , Grelina/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca
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