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1.
Blood Adv ; 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35679462

RESUMO

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nation-wide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China during 2005-2020, the mortality rate from ICH was 33.80% in ITP adults (48/142). We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10×109/L at ICH, a combination of serious infections, grade of preceding bleeding events and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic curves for the internal and external validation were 0.954 (95% CI: 0.910~0.998) and 0.942 (95% CI: 0.871~1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.

2.
Inquiry ; 59: 469580221093442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35613600

RESUMO

The novel coronavirus pandemic has led to morbidity and mortality throughout the world. Until now, it is a highly virulent contagion attacking the respiratory system in humans, especially people with chronic diseases and the elderly who are most vulnerable. A majority of afflicted are those suffering from cardiovascular and coronary diseases. In this review article, an attempt has been made to discuss and thoroughly review the mode of therapies that alleviate cardiac complications and complications due to hypercoagulation in patients infected with the SARS-CoV-2 virus. Presently a host of thrombolytic drugs are in use like Prourokinase, Retelapse, RhTNK-tPA and Urokinase. However, thrombolytic therapy, especially if given intravenously, is associated with a serious risk of intracranial haemorrhage, systemic haemorrhage, immunologic complications, hypotension and myocardial rupture. The effects of the SARS-CoV-2 virus upon the cardiovascular system and coagulation state of the body are being closely studied. In connection to the same, clinical prognosis and complications of thrombolytic therapy are being scrutinized. It is noteworthy to mention that myocardial oxygen supply/demand mismatch, direct myocardial cells injury and acute plaque rupture are the multiple mechanisms responsible for acute coronary syndrome and cardiac complications in Covid-19 infection. However, this review has limitations as data available in this context is limited, scattered and heterogenous that questions the reliability of the same. So, more multi-centric studies involving representative populations, carried out meticulously, could further assist in responding better to cardiac complications among Covid-19 patients.


Assuntos
COVID-19 , Doenças Cardiovasculares , Sistema Cardiovascular , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Reprodutibilidade dos Testes , SARS-CoV-2
3.
Haematologica ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35354250

RESUMO

Bone marrow(BM) endothelial progenitor cell(EPC) damage with unknown mechanism delays the repair of endothelial cells(ECs) and hematopoiesis recovery after chemo-radiotherapy. Herein, enhanced glycolytic enzyme PFKFB3 was demonstrated in the damaged BM EPCs of patients with poor graft function(PGF), a clinical model of EPC damage-associated poor hematopoiesis after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Moreover, glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one(3PO) alleviated the damaged BM EPCs of PGF patients in vitro. Consistently, PFKFB3 overexpression triggered BM EPC damage after 5FU treatment and impaired hematopoiesis-supporting ability in vitro. Mechanismly, PFKFB3 facilitated pro-apoptotic transcription factor FOXO3A and its downstream gene expressions, including p21, p27, FAS after 5FU treatment in vitro. Moreover, PFKFB3 induced NF-κB activation and its downstream adhesion molecule E-selectin expression, while reduced hematopoietic factor SDF-1 expression, which could be rescued by FOXO3A silence. Highly expressed PFKFB3 was found in damaged BM ECs of chemo-radiotherapy-induced myelosuppression murine models. Furthermore, the BM EC-specific PFKFB3 overexpression murine model demonstrated that PFKFB3 aggravated BM EC damage, and impaired hematopoiesis recovery after chemotherapy in vivo, which could be improved by 3PO, indicating a critical role of PFKFB3 in regulating BM EC damage. Clinically, PFKFB3-induced FOXO3A expression and NF-κB activation were confirmed to contribute to the damaged BM EPCs of patients with acute leukemia after chemotherapy. 3PO repaired the damaged BM EPCs by reducing FOXO3A expression and phospho-NF-κB p65 in patients after chemotherapy. In summary, our results reveal a critical role of PFKFB3 in triggering BM EPC damage and indicate that endothelial-PFKFB3 may be a potential therapeutic target for myelosuppressive injury.

4.
J Viral Hepat ; 29(5): 306-316, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35152507

RESUMO

Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly.


Assuntos
Hepatite B , Trombocitopenia , Hepatite B/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Contagem de Plaquetas , Prednisona , Proteínas Recombinantes/efeitos adversos , Esplenomegalia/complicações , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Trombopoetina/efeitos adversos
5.
Bone Marrow Transplant ; 57(4): 554-561, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35079139

RESUMO

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Estudos de Coortes , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Resultado do Tratamento
6.
Blood ; 139(3): 333-342, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34665865

RESUMO

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.


Assuntos
Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/uso terapêutico , Tretinoína/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , Rituximab/administração & dosagem , Prevenção Secundária , Tretinoína/administração & dosagem
7.
J Cell Mol Med ; 25(14): 6746-6759, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34132026

RESUMO

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.


Assuntos
Fibrilação Atrial/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteína Smad3/metabolismo , Transativadores/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo , Angiotensina II/toxicidade , Animais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etiologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Células Cultivadas , Fibrose , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Transativadores/metabolismo
8.
Bone Marrow Transplant ; 56(9): 2097-2107, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33846561

RESUMO

Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P = 0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P < 0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P < 0.001), and a high D-dimer level (>500 ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
9.
Transplant Cell Ther ; 27(3): 253.e1-253.e9, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33781524

RESUMO

Acute cholecystitis (AC) is a potentially fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, only limited information is available on its clinical features, outcomes, and risk management strategies. This retrospective, nested, case-control study included 6701 patients undergoing allo-HSCT at our center from January 2004 to June 2019. In total, 72 patients (1.1%) were diagnosed with AC; among these, acute acalculous cholecystitis had a slightly higher prevalence (42 patients, 58.3%). Patients with moderate and severe AC exhibited remarkably worse overall survival (P = .001) and non-relapse mortality (P = .011) than others. Survival of haploidentical HSCT recipients with AC was comparable to that for patients with human leukocyte antigen (HLA)-identical donors. Age ≥ 18 years, antecedent stage II to IV acute graft-versus-host disease, and total parenteral nutrition were identified as potential risk factors for AC following allo-HSCT, while haploidentical transplantations were not more susceptible to AC than HLA-identical HSCT. Based on these criteria, a risk score model was developed and validated to estimate the probability of AC following allo-HSCT. The model separates all patients into low-, intermediate-, and high-risk groups and thereby provides a basis for early detection of this complication in the management of allo-HSCT.


Assuntos
Colecistite Aguda , Transplante de Células-Tronco Hematopoéticas , Adolescente , Estudos de Casos e Controles , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Fatores de Risco
10.
J Cell Physiol ; 236(9): 6726-6741, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33611789

RESUMO

Thrombocytopenia is a common complication of human cytomegalovirus (HCMV) infection in immunocompromised hosts, which contributes to poor prognosis even in patients receiving antiviral treatment. Here, we investigated the megakaryo/thrombopoiesis process, including the involvement of the c-Mpl/IEX-1 pathway, after HCMV infection, identified receptors mediating the interaction between megakaryocytes (MKs) and HCMV, and explored novel therapeutic targets. Our data shows that HCMV directly infects megakaryocytes in patients with HCMV DNAemia and influences megakaryopoiesis via the c-Mpl/IEX-1 pathway throughout megakaryocyte maturation, apoptosis, and platelet generation in vivo and in vitro. After treatment with inhibitors of PDGFRα and αvß3, the HCMV infection rate in MKs was significantly reduced, suggesting that IMC-3G3 and anti-αvß3 are potential therapeutic alternatives for viral infection. In summary, our study proposes a possible mechanism and potential treatments for thrombocytopenia caused by HCMV infection and other viral diseases associated with abnormal hemostasis.


Assuntos
Citomegalovirus/fisiologia , Transplante de Células-Tronco Hematopoéticas , Integrina alfaVbeta3/metabolismo , Megacariócitos/virologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Trombopoetina/metabolismo , Transdução de Sinais , Trombopoese , Adolescente , Adulto , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Criança , Citomegalovirus/ultraestrutura , Infecções por Citomegalovirus/patologia , Regulação para Baixo , Feminino , Humanos , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Ploidias , Fatores de Risco , Receptor 2 Toll-Like/metabolismo , Transplante Homólogo , Adulto Jovem
11.
Ann Hematol ; 100(2): 505-516, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33389025

RESUMO

We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146-15.306, p < .001) was an independent risk factor for CNS relapse after allo-HSCT for AML. The 3-year overall survival (OS) for patients with CNS relapse was 60.3 ± 8.8%, which was significantly lower than that in the controls (81.5 ± 4.5%, p = .003). The incidence of CNS relapse was 1.64% for patients who received HID-HSCT and 2.55% for those who received ISD-HSCT (p = .193). There was no significant difference in OS between the HID-HSCT and ISD-HSCT subgroups among the patients with CNS relapse. In conclusion, CNS relapse is a rare but serious complication after allo-HSCT for AML, and the incidence and outcomes of patients with CNS relapse are comparable following HID-HSCT and ISD-HSCT.


Assuntos
Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Aloenxertos , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Taxa de Sobrevida
12.
Platelets ; 32(5): 633-641, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32614630

RESUMO

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.


Assuntos
Hemorragias Intracranianas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do Tratamento
13.
Blood Adv ; 4(22): 5846-5857, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232474

RESUMO

Infection is one of the primary causes of death from immune thrombocytopenia (ITP), and the lungs are the most common site of infection. We identified the factors associated with hospitalization for community-acquired pneumonia (CAP) in nonsplenectomized adults with ITP and established the [corrected] (ACPA) prediction model to predict the incidence of hospitalization for CAP. This was a retrospective study of nonsplenectomized adult patients with ITP from 10 large medical centers in China. The derivation cohort included 145 ITP inpatients with CAP and 1360 inpatients without CAP from 5 medical centers, and the validation cohort included the remaining 63 ITP inpatients with CAP and 526 inpatients without CAP from the other 5 centers. The 4-item ACPA model, which included age, Charlson Comorbidity Index score, initial platelet count, and initial absolute lymphocyte count, was established by multivariable analysis of the derivation cohort. Internal and external validation were conducted to assess the performance of the model. The ACPA model had an area under the curve of 0.853 (95% confidence interval [CI], 0.818-0.889) in the derivation cohort and 0.862 (95% CI, 0.807-0.916) in the validation cohort, which indicated the good discrimination power of the model. Calibration plots showed high agreement between the estimated and observed probabilities. Decision curve analysis indicated that ITP patients could benefit from the clinical application of the ACPA model. To summarize, the ACPA model was developed and validated to predict the occurrence of hospitalization for CAP, which might help identify ITP patients with a high risk of hospitalization for CAP.


Assuntos
Pneumonia , Púrpura Trombocitopênica Idiopática , Adulto , China , Hospitalização , Humanos , Pneumonia/epidemiologia , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos , Fatores de Risco
14.
Thromb Res ; 194: 168-175, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788111

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is regarded as a curative therapy for majority of hematologic malignancies and some non-malignant hematologic diseases. Venous thromboembolism (VTE) has become increasingly recognized as a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES: To show the characteristics of VTE after haploidentical donor hematopoietic stem cell transplantation (HID-HSCT) and make comparisons with matched related donor HSCT (MRD-HSCT). PATIENTS/METHODS: A retrospective nested case-control study design was used, cases with VTE and matched controls were selected, with 3534 patients underwent HID-HSCT and 1289 underwent MRD-HSCT. RESULTS: During follow-up, 114 patients with VTE were identified. The incidence of VTE in HID-HSCT group was similar to that of MRD-HSCT group (2.4% versus 2.3%, P = 0.92). In HID-HSCT group, VTE occurred at a median time of 92.5 days, which was earlier than MRD-HSCT group (243.5 days). For HID-HSCT, advanced disease status, cardiovascular risk factors, acute graft-versus-host disease (aGVHD), and relapse were the independent risk factors for VTE. For MRD-HSCT, cardiovascular risk factors, aGVHD, and relapse were associated with VTE. Overall survival (OS) of patients following HID-HSCT and MRD-HSCT were similar, but the OS in patients with VTE was significantly lower than patients without VTE. CONCLUSIONS: There was no statistical difference in the incidence of VTE after HID-HSCT compared with MRD-HSCT. The development of VTE adversely impacted the OS after allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tromboembolia Venosa , Estudos de Casos e Controles , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Irmãos , Tromboembolia Venosa/etiologia
15.
Ann Hematol ; 99(11): 2659-2670, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32734550

RESUMO

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/terapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
16.
J Cell Mol Med ; 24(16): 9204-9216, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32608128

RESUMO

Young donors are associated with a lower cumulative incidence of acute graft-vs-host disease (aGVHD) after allogenic haematopoietic stem cell transplantation (allo-HSCT) than old donors. Although grafts are harvested from healthy donors, it is unclear whether donor age is associated with aGVHD occurrence owing to its effect on cell compositions in grafts. Moreover, the differences in monocyte subsets in grafts between young and old donors and the association between monocyte subsets in bone marrow (BM) grafts and aGVHD remain to be elucidated. In the current study, non-classical monocytes and the CD4+ /CD8+ T cell ratio were remarkably decreased in BM grafts in donors <30 years old. Multivariate analysis further revealed that the level of non-classical monocytes in BM grafts (≥0.31 × 106 /kg) was an independent risk factor for the occurrence of II-IV aGVHD. In summary, our data indicate that non-classical monocytes in BM grafts may help identify patients at high risk for aGVHD after allo-HSCT. Although further validation is required, our results suggest that the low level of non-classical monocytes and a low ratio of CD4+ /CD8+ T cell in BM grafts may be correlated with the lower incidence of aGVHD in young donors.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Monócitos/citologia , Doadores de Tecidos/provisão & distribuição , Adolescente , Adulto , Fatores Etários , China/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Monócitos/classificação , Adulto Jovem
17.
Ann Hematol ; 99(7): 1643-1653, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32458063

RESUMO

To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/secundário , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irmãos , Transplante Haploidêntico , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/terapia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Teste de Histocompatibilidade/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Recidiva , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Resultado do Tratamento , Gêmeos Monozigóticos/estatística & dados numéricos , Adulto Jovem
18.
Bone Marrow Transplant ; 55(10): 2035-2042, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32305999

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is a gradually recognised neurological complication of allogenic haematopoietic stem cell transplantation (allo-HSCT). However, there is a paucity of information on PRES after haploidentical HSCT (haplo-HSCT). We performed a retrospective nested case-control study in patients following haplo-HSCT for malignant and nonmalignant haematologic diseases between January 2009 and December 2018 in our centre. A total of 45 patients were diagnosed with PRES after transplant, accounting for an incidence of 1.17%. Grades II to IV acute graft-versus-host disease (aGVHD) (HR 2.370, 95% CI 1.277-4.397, p = 0.006) and hypertension (HR 14.466, 95% CI 7.107-29.443, p < 0.001) were identified as risk factors for developing PRES after haplo-HSCT. There was no difference in overall survival (OS), disease-free survival (DFS), the cumulative incidence of relapse or nonrelapse mortality (NRM) between patients with PRES and controls without PRES following haplo-HSCT in either adults or children. All but one patient with PRES showed nearly complete clinical and neurologic recovery. In conclusion, PRES is a rare condition with benign outcomes following haplo-HSCT. Further multicentre prospective studies are needed to confirm the results and help to establish the standard therapy for posttransplant PRES.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndrome da Leucoencefalopatia Posterior , Adulto , Estudos de Casos e Controles , Criança , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Síndrome da Leucoencefalopatia Posterior/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
19.
Bone Marrow Transplant ; 55(11): 2087-2097, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32332920

RESUMO

Stroke is an important complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, few studies have been published to analyzed the occurrence and prognosis of stroke after allo-HSCT. From January 2007 to December 2018 in Peking University People's Hospital, 6449 patients received HSCT and there were 2.3% of patients diagnosed with stroke after allo-HSCT (hemorrhagic: 1.0%, ischemic: 1.3%). The median time to hemorrhagic and ischemic stroke after HSCT was 161 days and 137 days, respectively. In total, 8.4% of patients experienced neurological sequelae. The outcome was much worse in patients with stroke than in control subjects. The comparison of prognosis showed no statistical differences between patients with hemorrhagic stroke and those with ischemic stroke. Significant risk factors for hemorrhagic stroke were pretransplant central nervous system leukemia (CNSL), and delayed platelet engraftment. Risk factors associated with the occurrence of ischemic stroke included high-risk disease, prior venous thromboembolism (VTE), grade III-IV acute graft-versus-host disease (aGVHD), and thrombotic microangiopathy (TMA). Haplo-identical transplantation was not a risk factor for stroke and had no impact on the prognosis compared with HLA-matched HSCT. Altogether, these results show that stroke is a severe complication after allo-HSCT. The prognosis of posttransplant stroke did not differ between hemorrhagic and ischemic stroke.


Assuntos
Isquemia Encefálica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia
20.
Biol Blood Marrow Transplant ; 26(6): 1203-1209, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32105831

RESUMO

We aimed to investigate the frequency, risk factors, and outcome of active tuberculosis (TB) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective, nested, case-control study reviewed data from 6236 patients who received allo-HSCT from January 2008 to December 2018 at a single center; thirty-three patients (0.5%) with active TB and 99 controls without active TB after allo-HSCT were identified. We performed propensity score matching by randomly selecting 3 controls for each identified active TB patient according to the time of transplantation and follow-up period. History of pretransplant active TB previously treated and inactive at time of transplantation (P< .001) was an independent risk factor. No significant differences in overall survival (P= .342), nonrelapse mortality (P= .497), or incidence of relapse (P= .807) were found. Thirty (90.9%) patients were treated with 4-drug (isoniazid, rifampicin/three rifapentine, pyrazinamide, and ethambutol) or 3-drug combination first-line therapy, with a response rate of 76.7%. Twenty-six (78.8%) patients were treated with first-line and second-line combined therapy, and the response rate was 76.9%. Five (15.2%) patients developed hepatotoxicity. In conclusion, history of pretransplant active TB previously treated and inactive at time of transplantation was an independent risk factor of active TB after allo-HSCT. No significant differences in prognosis between the TB and control groups were found. More studies are needed to help develop standardized therapeutic strategies for patients with post-transplant TB.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tuberculose , Estudos de Casos e Controles , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Fatores de Risco , Tuberculose/etiologia
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