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1.
Zhonghua Nei Ke Za Zhi ; 58(11): 819-822, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31665857

RESUMO

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.


Assuntos
Anemia Aplástica/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/fisiologia , Cordão Umbilical/fisiologia , Doadores não Relacionados , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , China/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Humanos , Células-Tronco Mesenquimais , Células-Tronco de Sangue Periférico , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Cordão Umbilical/imunologia
2.
Medicine (Baltimore) ; 98(39): e17307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574859

RESUMO

To investigate the cognitive and psychological outcomes of pediatric allogeneic HSCT survivors in China.A total of 135 3 to 18 years old children and adolescents who underwent allo-HSCT and survived at least 3 months post-HSCT were recruited and completed the assessments. Cognitive and psychological functions were assessed via age-appropriate standardized measures. Clinical information was extracted from the medical records.Forty one 3 to 6 years old children completed Psychological Questionnaires for 3 to 6 years Children. The scores of 21(51.2%) children in cognitive development dimension, 18(43.9%) in motor development dimension, 16(39.0%) in language development and social development dimension, 15(36.6%) in emotion and will dimension and 14(34.1%) in living habits dimension were less than the standard. Fifty six 8 to 16 years old children and adolescents completed the Depression Self-rating Scale for Children and 9 (16.1%) of these met the criteria of depression. Sixty nine 7 to 16 years old children and adolescents completed the screening for Child Anxiety Related Disorders and 7 (10.1%) of these met the criteria of anxiety, especially social phobia and school phobia. Eighty nine 6 to 18 years old children and adolescents completed the Symptom Checklist-90 and 43.8% to 77.5% of these experienced mild symptoms like obsession-compulsion (77.5%), hostility (64%), and interpersonal sensitivity (60.7%). Children treated with total body irradiation (TBI) showed more cognitive impairments like motor deficits than those without TBI. Also older children and adolescents had more symptoms like psychoticism.These findings demonstrated cognitive and psychological late effects of pediatric allo-HSCT survivors in a single center in China and highlighted that the survivors conditioned with TBI had more cognitive impairments and older children and adolescents had more symptoms. Early intervention in these children and adolescents might minimize the cognitive losses and psychological effects.


Assuntos
Ansiedade , Disfunção Cognitiva , Depressão , Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias , Qualidade de Vida , Adolescente , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/prevenção & controle , Criança , Pré-Escolar , China/epidemiologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Depressão/diagnóstico , Depressão/etiologia , Depressão/prevenção & controle , Intervenção Médica Precoce/métodos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Destreza Motora , Avaliação de Processos e Resultados (Cuidados de Saúde) , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Técnicas Psicológicas , Sobreviventes/psicologia
3.
Expert Opin Drug Metab Toxicol ; 15(10): 803-811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595800

RESUMO

Introduction: Graft-versus-host disease (GVHD) is the most common complication of hematopoietic stem cell transplantation (HSCT); therefore, the prevention of GVHD is important for a successful treatment. Tacrolimus (Tac), a calcineurin inhibitor, has been widely used for the prophylaxis of GVHD in HSCT recipients. Areas covered: This review introduces phase II/III of clinical trials related with Tac's roles in the prevention of GVHD in HSCT. Furthermore, we discuss the normal ranges of Tac concentrations, pharmacogenetics, and drug interactions of Tac, as well as its side effects in adult HSCT recipients. Expert opinion: A series of studies has established the efficacy and safety of Tac alone or in combination with other agents in HSCT. However, successful administration of Tac is complicated by its narrow therapeutic window, inter-patient pharmacokinetic variability, and a spectrum of undesirable side effects. It is necessary to maintain concentrations of Tac within the desired ranges for GVHD prophylaxis. Moreover, various factors contribute to significant variability in Tac pharmacokinetics, including drug interactions and genomic variation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Tacrolimo/administração & dosagem , Adulto , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacocinética , Interações de Medicamentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Farmacogenética , Tacrolimo/efeitos adversos , Tacrolimo/farmacocinética
4.
Expert Opin Drug Saf ; 18(11): 1017-1030, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478398

RESUMO

Introduction: Human cytomegalovirus (HCMV) is a major contributor of morbidity and mortality, and its management is essential for the successful outcome of solid organ and hematopoietic stem cell transplantation. Areas covered: This review discusses the safety profiles of currently available and emerging antiviral drugs and the other strategies for HCMV prevention and treatment after transplantation. Expert opinion: Strategies for management of HCMV rely largely on the use of antiviral agents that inhibit viral DNA polymerase (ganciclovir/valganciclovir, foscarnet, and cidofovir/brincidofovir) and viral terminase complex (letermovir), with different types and degrees of adverse effects. An investigational agent, maribavir, exerts its anti-CMV effect through UL97 inhibition, and its safety profile is under clinical evaluation. In choosing the antiviral medication to use, it is important to consider these safety profiles in addition to overall efficacy. In addition to antiviral drugs, reduction of immunosuppression is often generally needed in the management of HCMV infection, but with a potential risk of allograft rejection or graft-versus-host disease. The use of HCMV-specific or non-specific intravenous immunoglobulins remains debated, while adoptive HCMV-specific T cell therapy remains investigational, and associated with unique set of adverse effects.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Infecções Oportunistas/prevenção & controle , Antivirais/efeitos adversos , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Infecções Oportunistas/virologia , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos
5.
Expert Opin Investig Drugs ; 28(9): 799-809, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398295

RESUMO

Introduction: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Mycosis fungoides and Sézary syndrome are the most common CTCL. Early stage disease follows a protracted course, carries a 5-year disease specific survival of 97% and can be treated with skin-directed therapies. Widespread, advanced disease has a 5-year OS of less than 25% and necessitates systemic treatment. Allogeneic stem cell transplantation is a potentially curative treatment option for advanced CTCL, however, transplant-related morbidity and mortality must be considered and a risk-benefit assessment performed on individual basis. Areas covered: Herein, we provide a review of investigative drugs in early-stage trials for the treatment of cutaneous CTCL, including topically applied immunomodulators such as replicating herpes virus or toll-like receptor 7/8 agonist resiquimod and systemic therapies with monoclonal antibodies, such as anti-CD47, recombinant cytotoxic interleukin 2 fusion protein anti-KIR3DL2 antibody and anti-miR-155 antibody. Expert Opinion: Among the reviewed drugs, resiquimod shows promising clinical efficacy with good tolerability in early CTCL. In refractory or relapsed disease, intratumoral anti-CD47-, anti-CCR4- and anti-KIR3DL2-antibodies show high response rates, however, latter two also show considerable toxicity. Larger trials are needed to better evaluate the discussed therapies.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/efeitos adversos , Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma Cutâneo de Células T/patologia , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Estadiamento de Neoplasias , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Taxa de Sobrevida
6.
J Cancer Res Clin Oncol ; 145(10): 2595-2604, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31410605

RESUMO

PURPOSE: Peripheral T cell lymphomas (PTCL) are a rare and heterogeneous group of aggressive non-Hodgkin lymphomas, showing a generally poor prognosis. In this retrospective analysis, we aimed to investigate the impact of autologous stem cell transplantation (autoSCT) in PTCL. METHODS: A retrospective analysis of 58 consecutive unselected PTCL patients aged 21-71 years undergoing autoSCT as first-line consolidation as well as in the relapse setting was performed. RESULTS: The median follow-up time was 67 months. A 5-year overall survival (OS) of 53% and a 5-year progression-free survival (PFS) after autoSCT of 44% was achieved. The overall relapse rate after autoSCT was 50%. On multivariate analysis, standard baseline characteristics such as age, disease stage and international prognostic index (IPI) score failed to predict outcome in our cohort. First-line treatment with autoSCT was not associated with a benefit in OS when compared to patients receiving autoSCT at relapse. Notably, autoSCT seemed to be a suitable approach even for older transplant-eligible patients (aged ≥ 60 years), with a similar 5-year OS of 49% when compared to younger patients. CONCLUSIONS: Our study suggests that autoSCT can achieve long-term survival in PTCL patients even after relapse and should also be considered for eligible older patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
7.
Cancer Sci ; 110(10): 3255-3266, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402561

RESUMO

Tyrosine kinase inhibitor (TKI) administration after allogeneic hematopoietic stem cell transplantation (HSCT) may carry a survival benefit in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Therefore, we investigated whether TKI prophylaxis for negative-minimal residual disease (MRD) after HSCT would improve patient outcomes in this nationwide retrospective cohort study. We included patients with Ph+ ALL who underwent their first allogeneic HSCT between 2001 and 2016, received TKI before HSCT, and achieved negative-MRD status within 180 days after HSCT. Of 850 patients for inclusion, 50 patients received TKI prophylaxis, mostly imatinib or dasatinib (median dose: 400 mg with imatinib and 40 mg with dasatinib). In a multivariate analysis, disease status at HSCT was the sole risk factor for relapse (hazard ratio, 3.58; P < .001 for positive-MRD with complete remission [CR] and hazard ratio, 6.13; P < .001 for active disease). TKI prophylaxis was not associated with a decreased risk of relapse or superior overall survival in either the whole cohort or in the analysis limited to negative-MRD or positive-MRD with CR1 at HSCT. Meanwhile, TKI prophylaxis limited to dasatinib might be associated with a decreased risk of relapse (hazard ratio, 0.34; P = .140), unlike imatinib. Alternative strategies using new-generation TKI for high-risk patients are warranted to improve the outcomes after allogeneic HSCT.


Assuntos
Proteínas de Fusão bcr-abl/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Adolescente , Adulto , Idoso , Terapia Combinada , Dasatinibe/administração & dosagem , Dasatinibe/farmacologia , Feminino , Proteínas de Fusão bcr-abl/efeitos dos fármacos , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/farmacologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/farmacologia , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
8.
Transplant Proc ; 51(6): 1982-1989, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399180

RESUMO

OBJECTIVE: Human leukocyte antigen match is the most important donor factor affecting transplant outcome. The HLA-DPB1 mismatch on the clinical outcome of hematopoietic stem cell transplant (HSCT) is less clear. This study is the first meta-analysis to investigate the impact of HLA-DPB1 loci mismatch on clinical outcome after unrelated donor HSCT for hematologic malignant disease. METHODS: We electronically searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and a related database (January 1995-December 2018) for all relevant articles. Comparative studies were carried out to investigate the impact of HLA-DPB1 loci mismatch on clinical outcome after unrelated donor HSCT, that is, the disease-free survival, engraftment, graft-vs-host disease, relapse, and transplant-related mortality (TRM). We performed a meta-analysis using Review Manager 5.3.5 software and adopted funnel plot regression to assess the publication bias. RESULTS: A total of 1570 articles were retrieved; 21 studies including 27,852 patients were assessed. Pooled comparisons of studies found that the HLA-DPB1-mismatched group had a lower rate of disease-free survival than the DPB1-matched group and lower overall survival in non-T cell-depleted transplant than the DPB1-matched group. The DPB1-mismatched group has higher incidence of acute graft-vs-host disease (aGVHD) and severe (≥ III degree) aGVHD, lower relapse rate, and higher TRM. Moreover, compared with 1-antigen mismatch, 2-antigen mismatch in DPB1 had a higher risk of TRM and a lower relapse rate, and the nonpermissive DPB1 mismatch had significantly higher rate of severe aGvHD and lower rate of disease relapse. CONCLUSIONS: This analysis confirmed that HLA-DPB1 has important influence on survival and transplant-related complications during unrelated donor HSCT, and HLA-DPB1 donor selection strategies have been proposed based on personalized algorithm.


Assuntos
Incompatibilidade de Grupos Sanguíneos/mortalidade , Cadeias beta de HLA-DP/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Adulto , Incompatibilidade de Grupos Sanguíneos/imunologia , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Doadores não Relacionados
9.
Epidemiol Mikrobiol Imunol ; 68(2): 71-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398979

RESUMO

INTRODUCTION: The optimal dosage of anti-thymocyte globulin (ATG) may influence the outcome of patients after allogenic haematopoietic stem cell transplantation (HSCT). The aim of our study was to analyse human cytomegalovirus (CMV) infection data, incidence of graft-versus-host disease and other clinical endpoints comparing two patients cohorts that were administered two different Thymoglobuline Genzyme doses as part of the HSCT conditioning regimen. MATERIALS AND METHODS: Total of 65 adult patients received ATG (7.5 mg/kg or 6 mg/kg) as a part of the fludarabine/busulfan/ATG conditioning regimen. CMV DNAemia was monitored after HSCT using quantitative real-time PCR and preemptive treatment was started for viral loads above 1000 cp/ml. RESULTS: The mild ATG dose reduction extended the time to the first CMV detection after transplantation (28 days for 7.5 mg/kg dose vs. 40 days for 6 mg/kg dose, p = 0.04). But it did not reduce the incidence or influence first anti-CMV treatment onset, the initial viral load, peak viral load in whole blood or the antiviral therapy parameters (all p 0.18). No impact of ATG dose reduction on incidence of graft-versus-host-disease, relapse of underlying disease or mortality within first year after transplantation (all p 0.32) were observed. CONCLUSIONS: The reduced ATG dosages can allow lower toxicity of conditioning regimen while keeping the performance.


Assuntos
Soro Antilinfocitário , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adulto , Soro Antilinfocitário/administração & dosagem , Estudos de Coortes , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento
10.
Rev Med Chil ; 147(4): 437-443, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344204

RESUMO

BACKGROUND: Hodgkin lymphoma has a high rate of curability, even in advanced stages. AIM: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. MATERIAL AND METHODS: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. RESULTS: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. CONCLUSIONS: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Chile , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
11.
Transplant Proc ; 51(6): 1990-1993, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303412

RESUMO

BACKGROUND: The psychological distress experienced by patients scheduled for hematopoietic stem cell transplantation (HSCT) is of clinical concern. However, distress experienced by patients scheduled for HLA-haploidentical HSCT vs that of patients scheduled for other types of matched HSCT is unknown. We conducted a retrospective study to clarify whether the type of HSCT influences the appearance of psychological distress in patients anticipating HSCT. METHODS: One hundred fifty-seven patients who had undergone any of 4 types of HSCT at Tokyo Metropolitan Komagome Hospital between October 2013 and September 2016 and had completed the Profile of Mood States (POMS) questionnaire within 2 weeks before the procedure were included. We computed T-scores for the tension-anxiety (TA) and depression (D) subscales, took scores ≥ 60 to represent mood disturbance of clinical concern, and examined scores and other clinical variables in relation to each procedure. RESULTS: Twenty-two (14.0%) patients had a POMS-TA score ≥ 60, and 26 (16.6%) had a POMS-D score ≥ 60. The numbers of POMS-TA and POMS-D scores ≥ 60 did not differ significantly with respect to age, sex, leukemia type, number of previous transplants, disease status, comorbidity index, or transplant type. A multivariate logistic regression analysis confirmed the absence of an influence of the type of HSCT on the incidence of POMS-TA or POMS-D scores ≥60. CONCLUSION: Attention should be paid to the matter of psychological distress in patients with leukemia who will be treated by HSCT, even HLA-haploidentical HSCT. Such patients need psychological support, especially during the waiting period immediately prior to the transplantation procedure.


Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Leucemia/psicologia , Estresse Psicológico/etiologia , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia
12.
Medicine (Baltimore) ; 98(29): e16222, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335672

RESUMO

RATIONALE: HIV-related lymphoma, especially non-Hodgkin lymphoma, is one of the most common malignant tumors in HIV/acquired immune deficiency syndrome (AIDS) patients. Autologous hematopoietic stem cell transplantation (AHSCT) for the patients with Burkitt lymphoma (BL) is needed to be further explored. PATIENT CONCERNS: A 57-year-old man was hospitalized with intermittent pain on upper abdomen and melena for >1 month. DIAGNOSIS: HIV antibody testing was positive. The upper gastrointestinal endoscopy was performed and histopathology and immunohistochemistry revealed BL. INTERVENTIONS: Highly effective antiretroviral therapy and sixth cycles of chemotherapy were administered, followed by autologous hematopoietic stem cell transplantation. OUTCOMES: The patient has had tumor-free survival for >6 years with normal CD4+ T cell counts and HIV viral load below the lowest detection LESSONS:: The patient was treated with AHSCT followed complete remission after chemotherapy and achieved long-term disease-free survival. AHSCT may be a promising way for clinical cure of HIV-related BL.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Linfoma de Burkitt , Infecções por HIV , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt/complicações , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Intervalo Livre de Doença , Endoscopia Gastrointestinal/métodos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento , Carga Viral/métodos
13.
Medicine (Baltimore) ; 98(29): e16498, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335716

RESUMO

RATIONALE: Relapse is the main cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, there are no efficient methods to prevent relapse after allo-HSCT. Chimeric antigen receptor T (CAR-T) cells have achieved favorable outcomes in the treatment of refractory/relapsed acute lymphoblastic leukemia (ALL) because of their strong anti-leukemia activity. However, it is unclear whether the CAR-T cells constructed using viral systems can be used as preventive infusions to prevent relapse after haploidentical HSCT. PATIENT CONCERNS: Two patients with ALL with high risk received haploidentical HSCT. DIAGNOSES: Two patients were diagnosed with ALL with high risk. INTERVENTIONS: Patients received preventive infusion of donor-derived CAR-T cells constructed using viral systems on day 60 after haploidentical HSCT. OUTCOMES: The CAR-T cells were continually detected, and no graft versus host disease developed. The two patients survived with disease-free for 1 year and 6 months, respectively. LESSONS: Preventive infusion of donor-derived CAR-T cells after haploidentical HSCT may be safe and that immunosuppressors may not affect the proliferation of CAR-T cells.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Transplante Haploidêntico , Adulto , Pré-Escolar , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Masculino , Doadores de Tecidos
14.
Life Sci ; 232: 116598, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247209

RESUMO

Hematopoietic stem cells (HSCs) are a rare cell population in adult bone marrow, mobilized peripheral blood, and umbilical cord blood possessing self-renewal and differentiation capability into a full spectrum of blood cells. Bone marrow HSC transplantation has been considered as an ideal option for certain disorders treatment including hematologic diseases, leukemia, immunodeficiency, bone marrow failure syndrome, genetic defects such as thalassemia, sickle cell anemia, autoimmune disease, and certain solid cancers. Ex vivo proliferation of these cells prior to transplantation has been proposed as a potential solution against limited number of stem cells. In such culture process, MSCs have also been shown to exhibit high capacity for secretion of soluble mediators contributing to the principle biological and therapeutic activities of HSCs. In addition, endothelial cells have been introduced to bridge the blood and sub tissues in the bone marrow, as well as, HSCs regeneration induction and survival. Cell culture in the laboratory environment requires cell growth strict control to protect against contamination, symmetrical cell division and optimal conditions for maximum yield. In this regard, microfluidic systems provide culture and analysis capabilities in micro volume scales. Moreover, two-dimensional cultures cannot fully demonstrate extracellular matrix found in different tissues and organs as an abstract representation of three dimensional cell structure. Microfluidic systems can also strongly describe the effects of physical factors such as temperature and pressure on cell behavior.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Animais , Células da Medula Óssea/citologia , Técnicas de Cultura de Células/métodos , Técnicas de Cocultura , Células Endoteliais/citologia , Sangue Fetal/citologia , Humanos , Células-Tronco Mesenquimais/citologia
15.
Drugs ; 79(10): 1103-1134, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31209777

RESUMO

Mucopolysaccharidoses (MPS) are inborn errors of metabolism produced by a deficiency of one of the enzymes involved in the degradation of glycosaminoglycans (GAGs). Although taken separately, each type is rare. As a group, MPS are relatively frequent, with an overall estimated incidence of around 1 in 20,000-25,000 births. Development of therapeutic options for MPS, including hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT), has modified the natural history of many MPS types. In spite of the improvement in some tissues and organs, significant challenges remain unsolved, including blood-brain barrier (BBB) penetration and treatment of lesions in avascular cartilage, heart valves, and corneas. Newer approaches, such as intrathecal ERT, ERT with fusion proteins to cross the BBB, gene therapy, substrate reduction therapy (SRT), chaperone therapy, and some combination of these strategies may provide better outcomes for MPS patients in the near future. As early diagnosis and early treatment are imperative to improve therapeutic efficacy, the inclusion of MPS in newborn screening programs should enhance the potential impact of treatment in reducing the morbidity associated with MPS diseases. In this review, we evaluate available treatments, including ERT and HSCT, and future treatments, such as gene therapy, SRT, and chaperone therapy, and describe the advantages and disadvantages. We also assess the current clinical endpoints and biomarkers used in clinical trials.


Assuntos
Mucopolissacaridoses/tratamento farmacológico , Adolescente , Barreira Hematoencefálica/metabolismo , Criança , Pré-Escolar , Terapia Combinada/métodos , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Terapia de Reposição de Enzimas/métodos , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Recém-Nascido , Proteínas de Fusão de Membrana/química , Proteínas de Fusão de Membrana/metabolismo , Permeabilidade , Resultado do Tratamento , Adulto Jovem
16.
Medicine (Baltimore) ; 98(24): e15662, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192909

RESUMO

Primary adrenal lymphoma (PAL) is a rare entity of lymphoma with dismal prognosis using systemic chemotherapy. More clinical reports are needed to guide the treatment for PAL.We performed a retrospective analysis of 20 patients diagnosed with PAL who presented to our center between January 2005 and January 2014.Median age at presentation was 48 years (range: 27-73) with a male-to-female ratio of 7:3. Bilateral and right-sided adrenal involvement were seen in 11 of 20 and 7 of 20 patients, respectively. Adrenal insufficiency (AI) was seen in 6 of 10 evaluated patients. Diffuse large B cell lymphoma (DLBCL) was the most common immunophenotype (85.0%). Two patients died due to rapid disease progression before treatment. Two patients received autologous stem cell transplantation as consolidation therapy. All patients received prophylactic intrathecal chemotherapy. The estimated 5-year overall survival (OS) and progression-free survival (PFS) were 52.5% [95% confidence interval (95% CI: 28.2-72.0)] and 53.2% (95% CI: 29.0-72.5), respectively.These findings suggest that PAL should always be considered in differential diagnosis of adrenal mass with AI. Despite the contrasting previous reports, long-term prognosis of PAL is not necessarily inferior to that of non-Hodgkin lymphoma in general.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Difuso de Grandes Células B/terapia , Neoplasias das Glândulas Suprarrenais/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Progressão da Doença , Esquema de Medicação , Tratamento Farmacológico , Feminino , Humanos , Injeções Espinhais , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
17.
Lancet ; 394(10192): 29-38, 2019 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171419

RESUMO

BACKGROUND: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma. METHODS: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites. Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group). The primary endpoint of part 1 was stringent complete response assessed 100 days after transplantation. Part 2 (maintenance) is ongoing. The trial is registered with ClinicalTrials.gov, number NCT02541383. FINDINGS: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled at 111 European sites and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542). At day 100 after transplantation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10-5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33-0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23-0·80). The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). INTERPRETATION: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma. FUNDING: The Intergroupe Francophone du Myélome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
18.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151230

RESUMO

Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut, liver, lungs, or brain. In addition to organ involvement, CMV reactivation can exert indirect effects such as immunosuppression or graft failure that may result in the development of concurrent infectious complications. Currently, preemptive therapy, which is based on PCR-based monitoring of CMV from blood, is a mainstay enabling improvement in CMV-related outcomes. During the past decades, new antiviral drugs, clinical trials for prophylaxis in high-risk groups, and vaccines for preventing CMV infection have been introduced. In addition, data for immunologic monitoring and adoptive immunotherapy have also been accumulated. Here, we review the current status and recent updates in this field, with future perspectives including immunotherapy in HSCT recipients.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Citomegalovirus/imunologia , Vacinas contra Citomegalovirus/administração & dosagem , Vacinas contra Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Imunoterapia , Vigilância em Saúde Pública , Padrão de Cuidado , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento
19.
Hematology ; 24(1): 225-231, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31081725

RESUMO

BACKGROUND/OBJECTIVE: Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cured. We should better control tumors with initial treatment for patients with advanced stage HL whose interim positron emission tomography/computed tomography (PET/CT) was positive. The objective of our study was to confirm the superiority of autologous hematopoietic stem cell transplantation (ASCT) therapy in these patients. METHODS: Eighty-nine HL patients with stage III-IV, international prognostic score (IPS) ≥3 and Deauville more than 3° at the interim PET/CT were analyzed. Forty five patients received ASCT. The other 44 patients received two cycles DHAP chemotherapy. RESULTS: The 3-year overall survival (OS) of patients who received ASCT was 91.1%, and for the patients who received chemotherapy, it was 72.7% (P = 0.025). The 3-year progression free survival (PFS) of patients in the ASCT group was 88.9%, but for patients in the chemotherapy group, it was only 70.5%(P = 0.017). No patient died of toxicity from ASCT. Additionally, there was no difference in the rates of secondary malignancies between the ASCT and chemotherapy groups. Extranodal and bone marrow involvement were poor prognostic factors, while ASCT was a good prognostic factor. CONCLUSION: The use of ASCT as a first-line consolidation treatment could improve outcome of patients with advanced-stage high risk HL whose interim PET/CT was positive.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco
20.
Ann Hematol ; 98(8): 1877-1883, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144019

RESUMO

Secondary poor graft function (sPGF) is defined as secondary cytopenia after initial engraftment of allogeneic stem cell transplantation (allo-SCT). It has been shown to be associated with poor prognosis; however, there are very few reports on the incidence, risk factors, and outcomes of sPGF. Between January 2015 and December 2015, 564 patients, who received transplantation at Peking University People's Hospital, were retrospectively reviewed. Among the 490 patients who achieved initial engraftment of both neutrophils and platelets, 28 patients developed sPGF. The cumulative incidence of sPGF on day 100 was 5.7%. The median time of sPGF was 54.5 (34-91) days after transplantation. Low (< median) CD34+ cell dose (p = 0.019, HR 3.07 (95% CI, 1.207-7.813)), Epstein-Barr Virus (EBV) reactivation (p = 0.009, HR 3.648 (95%CI, 1.382-9.629)), and cytomegalovirus (CMV) reactivation (p = 0.003, HR 7.827 (95%CI, 2.002-30.602)) were identified as independent risk factors for sPGF. There was no significant difference in PGF incidence between the matched sibling donor (MSD) group and haploidentical donor (HID) group (p = 0.44). The overall survival of patients with sPGF at 1 year after transplantation was significantly poorer than that of patients with good graft function (GGF) (50.5% versus 87.2%, p < 0.001). In conclusion, sPGF developed in 5.7% patients after allo-SCT, especially in patients with CMV, EBV reactivation, or infusion with a low dose of CD34+ cells. The prognosis of sPGF is still poor owing to a lack of standard treatment.


Assuntos
Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/virologia , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Ativação Viral/imunologia , Adolescente , Adulto , Idoso , Antígenos CD34/imunologia , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/virologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/virologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/virologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Haploidêntico
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