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[PMID]:29455234
[Au] Autor:Wang S; Wang X; Liu M; Bai O
[Ad] Endereço:Department of Hematology, The First Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, People's Republic of China.
[Ti] Título:Blastic plasmacytoid dendritic cell neoplasm: update on therapy especially novel agents.
[So] Source:Ann Hematol;97(4):563-572, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. Most patients present with asymptomatic skin lesions as the first symptom and has a high frequency of bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co-expression without common lymphoid or myeloid lineage markers. There is no consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive to chemotherapy but the median event-free survival is very short. Allogeneic stem cell transplantation may improve the prognosis of BPDCN but the rate of relapse is still high. There are no specific targeted agents approved for patients with BPDCN, but advances in the understanding of the pathobiology of BPDCN and the results of early clinical studies have revealed novel targets and potentially effective agents. Novel targeted therapies may improve outcomes for patients with BPDCN in the future.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Células Dendríticas/efeitos dos fármacos
Drogas em Investigação/uso terapêutico
Neoplasias Hematológicas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linhagem Celular Tumoral
Neoplasias do Sistema Nervoso Central/diagnóstico
Neoplasias do Sistema Nervoso Central/prevenção & controle
Neoplasias do Sistema Nervoso Central/secundário
Células Dendríticas/patologia
Drogas em Investigação/farmacologia
Neoplasias Hematológicas/diagnóstico
Neoplasias Hematológicas/patologia
Neoplasias Hematológicas/cirurgia
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Seres Humanos
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drugs, Investigational)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180219
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3259-z


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[PMID]:29381772
[Au] Autor:Chen D; Zhou D; Guo D; Xu P; Chen B
[Ad] Endereço:Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People's Republic of China.
[Ti] Título:Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis.
[So] Source:PLoS One;13(1):e0191955, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Haploidentical and human leukocyte antigen (HLA)-identical sibling hematopoietic stem transplantation are two main ways used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable progress has been made in haploidentical allo-HSCT (HID-SCT), and some institutions found HID-SCT had similar outcomes as HLA-identical sibling allo-HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic malignancies, we performed this meta-analysis. METHODS: Relevant articles published prior to February 2017 were searched on PubMed. Two reviewers assessed the quality of the included studies and extracted data independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis. RESULTS: Seven studies including 1919 patients were included. The rate of platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70-3.93, P < 0.00001). The risk of acute graft-versus-host disease (GVHD) is significantly higher after HID-SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42-2.49, P < 0.00001), but the relapse rate is lower in HID-SCT group (OR = 0.70, 95% CI = 0.55-0.90, P = 0.005). The incidence rates of overall survival (OS) and disease-free-survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISD-SCT are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08-1.62, P = 0.006; OR = 1.25, 95% CI = 1.03-1.52, P = 0.02). There is no significant difference in transplantation related mortality (TRM) rate after HID-SCT and ISD-SCT. CONCLUSION: After myeloablative conditioning, patients receiving ISD-SCT have a faster engraftment, lower acute GVHD and longer life expectancy compared to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA-identical sibling donor available.
[Mh] Termos MeSH primário: Doenças Hematológicas/terapia
Condicionamento Pré-Transplante
[Mh] Termos MeSH secundário: Antígenos HLA/imunologia
Haplótipos
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Análise de Sobrevida
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191955


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[PMID]:29349655
[Au] Autor:Lo WJ; Lin CL; Chang YC; Bai LY; Lin CY; Liang JA; Li LY; Chao LM; Chiu CF; Chen CM; Yeh SP
[Ad] Endereço:Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
[Ti] Título:Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.
[So] Source:Ann Hematol;97(4):697-707, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI.
[Mh] Termos MeSH primário: Apoptose/efeitos da radiação
Células da Medula Óssea/efeitos da radiação
Aberrações Cromossômicas/efeitos da radiação
Células-Tronco Hematopoéticas/efeitos da radiação
Células Mesenquimais Estromais/efeitos da radiação
Lesões por Radiação/patologia
Irradiação Corporal Total/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Células-Tronco Adultas/efeitos da radiação
Células da Medula Óssea/citologia
Células da Medula Óssea/patologia
Diferenciação Celular/efeitos da radiação
Proliferação Celular/efeitos da radiação
Células Cultivadas
China
Transtornos Cromossômicos/etiologia
Transtornos Cromossômicos/patologia
Feminino
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/patologia
Hospitais Universitários
Seres Humanos
Leucemia/patologia
Leucemia/terapia
Masculino
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/patologia
Necrose
Lesões por Radiação/etiologia
Condicionamento Pré-Transplante/efeitos adversos
Células Tumorais Cultivadas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3231-y


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[PMID]:28466385
[Au] Autor:Atilla E; Atilla PA; Bozdag SC; Yuksel MK; Toprak SK; Topcuoglu P; Akay BN; Sanli H; Gurman G; Ozcan M
[Ad] Endereço:BMT Unit, Department of Hematology, Cebeci Hospital, School of Medicine, Ankara University, Dikimevi, 06590, Ankara, Turkey. erdenatilla@gmail.com.
[Ti] Título:Allogeneic hematopoietic stem cell transplantation for refractory mycosis fungoides (MF) and Sezary syndrome (SS).
[So] Source:Int J Hematol;106(3):426-430, 2017 Sep.
[Is] ISSN:1865-3774
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Cutaneous T cell lymphoma is a heterogeneous group of lymphoproliferative disorders with different clinical behavior and prognosis in which malignant T cells accumulate in the skin. In the relapsed/refractory stage, treatment strategy varies depending on clinical perspective. We retrospectively evaluated advanced stage relapse or refractory mycosis fungoides and Sezary syndrome patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our hospital. The overall response rate was 25%, while the disease progressed and relapsed after transplant in 38% of patients. Allo-HSCT may be a reasonable treatment option in the relapsed/refractory stage.
[Mh] Termos MeSH primário: Aloenxertos
Transplante de Células-Tronco Hematopoéticas
Micose Fungoide/terapia
Síndrome de Sézary/terapia
Neoplasias Cutâneas/terapia
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Masculino
Meia-Idade
Recidiva Local de Neoplasia
Estudos Retrospectivos
Neoplasias Cutâneas/reabilitação
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1007/s12185-017-2245-x


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Registro de Ensaios Clínicos
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[PMID]:29211658
[Au] Autor:Marty FM; Ljungman P; Chemaly RF; Maertens J; Dadwal SS; Duarte RF; Haider S; Ullmann AJ; Katayama Y; Brown J; Mullane KM; Boeckh M; Blumberg EA; Einsele H; Snydman DR; Kanda Y; DiNubile MJ; Teal VL; Wan H; Murata Y; Kartsonis NA; Leavitt RY; Badshah C
[Ad] Endereço:From the Dana-Farber Cancer Institute and Brigham and Women's Hospital (F.M.M.) and Tufts Medical Center and Tufts University School of Medicine (D.R.S.), Boston; Karolinska University Hospital and Karolinska Institutet, Stockholm (P.L.); University of Texas M.D. Anderson Cancer Center, Houston (R.F
[Ti] Título:Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.
[So] Source:N Engl J Med;377(25):2433-2444, 2017 12 21.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV-terminase complex. METHODS: In this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk. Letermovir was administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). Patients in whom clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) developed discontinued the trial regimen and received anti-CMV treatment. The primary end point was the proportion of patients, among patients without detectable CMV DNA at randomization, who had clinically significant CMV infection through week 24 after transplantation. Patients who discontinued the trial or had missing end-point data at week 24 were imputed as having a primary end-point event. Patients were followed through week 48 after transplantation. RESULTS: From June 2014 to March 2016, a total of 565 patients underwent randomization and received letermovir or placebo beginning a median of 9 days after transplantation. Among 495 patients with undetectable CMV DNA at randomization, fewer patients in the letermovir group than in the placebo group had clinically significant CMV infection or were imputed as having a primary end-point event by week 24 after transplantation (122 of 325 patients [37.5%] vs. 103 of 170 [60.6%], P<0.001). The frequency and severity of adverse events were similar in the two groups overall. Vomiting was reported in 18.5% of the patients who received letermovir and in 13.5% of those who received placebo; edema in 14.5% and 9.4%, respectively; and atrial fibrillation or flutter in 4.6% and 1.0%, respectively. The rates of myelotoxic and nephrotoxic events were similar in the letermovir group and the placebo group. All-cause mortality at week 48 after transplantation was 20.9% among letermovir recipients and 25.5% among placebo recipients. CONCLUSIONS: Letermovir prophylaxis resulted in a significantly lower risk of clinically significant CMV infection than placebo. Adverse events with letermovir were mainly of low grade. (Funded by Merck; ClinicalTrials.gov number, NCT02137772 ; EudraCT number, 2013-003831-31 .).
[Mh] Termos MeSH primário: Acetatos/uso terapêutico
Antivirais/uso terapêutico
Infecções por Citomegalovirus/prevenção & controle
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Quinazolinas/uso terapêutico
[Mh] Termos MeSH secundário: Acetatos/efeitos adversos
Adolescente
Adulto
Idoso
Antivirais/efeitos adversos
Citomegalovirus/genética
Citomegalovirus/isolamento & purificação
Infecções por Citomegalovirus/epidemiologia
Infecções por Citomegalovirus/etiologia
DNA Viral/sangue
Método Duplo-Cego
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Quinazolinas/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIC246); 0 (Acetates); 0 (Antiviral Agents); 0 (DNA, Viral); 0 (Quinazolines)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171207
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1706640


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[PMID]:28453848
[Au] Autor:Kakiuchi S; Tsuji M; Nishimura H; Yoshikawa T; Wang L; Takayama-Ito M; Kinoshita H; Lim CK; Fujii H; Yamada S; Harada S; Oka A; Mizuguchi M; Taniguchi S; Saijo M
[Ad] Endereço:Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan.
[Ti] Título:Association of the Emergence of Acyclovir-Resistant Herpes Simplex Virus Type 1 With Prognosis in Hematopoietic Stem Cell Transplantation Patients.
[So] Source:J Infect Dis;215(6):865-873, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Antiviral-resistant herpes simplex virus type 1 (HSV-1) has been recognized as an emerging clinical problem among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A prospective observational study was conducted at a hematological center over a 2-year period. Oropharyngeal swab samples were serially collected each week from 1 week before and up to 100 days after HSCT and were tested for virus isolation. The HSV-1 isolates were tested for sensitivity to acyclovir (ACV). The prognosis of patients with ACV-resistant (ACVr) HSV-1 and the genetic background of the ACVr HSV-1 isolates were assessed. Results: Herpes simplex virus type 1 was isolated in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir-resistant HSV-1 emerged in 11 of these 39 patients (28%). The 100-day death rates of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1 shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%, respectively. Patients with HSV-1, including ACVr HSV-1, shedding showed a significantly higher mortality rate. Relapsed malignancies were a significant risk factor for the emergence of ACVr HSV-1. Acyclovir resistance was attributable to viral thymidine kinase and DNA polymerase mutations in 6 and 5 patients, respectively. Conclusions: Herpes simplex virus type 1, including ACVr HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV disease did not always occur. Patients with relapsed malignancies were at especially high risk for the emergence of ACVr HSV-1.
[Mh] Termos MeSH primário: Aciclovir/uso terapêutico
Antivirais/uso terapêutico
Farmacorresistência Viral
Transplante de Células-Tronco Hematopoéticas/mortalidade
Herpes Simples/tratamento farmacológico
Herpesvirus Humano 1/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
DNA Polimerase Dirigida por DNA/genética
Feminino
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Herpes Simples/virologia
Herpesvirus Humano 1/isolamento & purificação
Seres Humanos
Japão
Masculino
Testes de Sensibilidade Microbiana
Meia-Idade
Análise Multivariada
Complicações Pós-Operatórias/virologia
Prognóstico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Recidiva
Taxa de Sobrevida
Timidina Quinase/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antiviral Agents); EC 2.7.1.21 (Thymidine Kinase); EC 2.7.7.7 (DNA-Directed DNA Polymerase); X4HES1O11F (Acyclovir)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix042


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[PMID]:29178837
[Au] Autor:Spinozzi G; Calabria A; Brasca S; Beretta S; Merelli I; Milanesi L; Montini E
[Ad] Endereço:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
[Ti] Título:VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.
[So] Source:BMC Bioinformatics;18(1):520, 2017 Nov 25.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. RESULTS: Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). CONCLUSIONS: We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).
[Mh] Termos MeSH primário: Interface Usuário-Computador
[Mh] Termos MeSH secundário: Algoritmos
Terapia Genética
Vetores Genéticos/genética
Vetores Genéticos/metabolismo
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/metabolismo
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Lentivirus/genética
Lentivirus/fisiologia
Alinhamento de Sequência
Internalização do Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1937-9


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[PMID]:28461213
[Au] Autor:Vrooman LM; Millard HR; Brazauskas R; Majhail NS; Battiwalla M; Flowers ME; Savani BN; Akpek G; Aljurf M; Bajwa R; Baker KS; Beitinjaneh A; Bitan M; Buchbinder D; Chow E; Dandoy C; Dietz AC; Diller L; Gale RP; Hashmi SK; Hayashi RJ; Hematti P; Kamble RT; Kasow KA; Kletzel M; Lazarus HM; Malone AK; Marks DI; O'Brien TA; Olsson RF; Ringden O; Seo S; Steinberg A; Yu LC; Warwick A; Shaw B; Duncan C
[Ad] Endereço:Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts. Electronic address: lynda_vrooman@dfci.harvard.edu.
[Ti] Título:Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age.
[So] Source:Biol Blood Marrow Transplant;23(8):1327-1334, 2017 Aug.
[Is] ISSN:1523-6536
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age.
[Mh] Termos MeSH primário: Doença Enxerto-Hospedeiro/mortalidade
Doença Enxerto-Hospedeiro/terapia
Neoplasias Hematológicas/mortalidade
Neoplasias Hematológicas/terapia
Transplante de Células-Tronco Hematopoéticas
[Mh] Termos MeSH secundário: Fatores Etários
Aloenxertos
Pré-Escolar
Doença Crônica
Intervalo Livre de Doença
Feminino
Seguimentos
Seres Humanos
Lactente
Masculino
Taxa de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28460445
[Au] Autor:Lv W; Fan Z; Huang F; Xu N; Xuan L; GuopanYu; Jiang Q; Zhou H; Lin R; Zhang X; Sun J; Liu Q
[Ad] Endereço:Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 China.
[Ti] Título:Autoimmune hematological diseases following haploidentical donor hematopoietic stem cell Transplant compared with matched sibling and unrelated donor.
[So] Source:Oncotarget;8(16):26505-26514, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Autoimmune hematological diseases (AHDs) occur more frequently than other autoimmune complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and are often refractory to treatment. This study was to analyze the incidence and risk factors of AHDs as well as their response to treatment . Four hundred and forty-five adult malignant hematopoietic disorders underwent allo-HSCT were enrolled in this retrospective study, including 124 haploidentical donor (HRD), 140 unrelated donor (MUD) and 181 HLA-matched sibling donor (MSD) transplants. Twelve patients developed AHDs, including 6 autoimmune hemolytic anemia and 6 Evans syndrome. Evans syndrome all occurred in HRD transplants. The 3-year cumulative incidence of AHDs was 4.0 ± 1.3%, and HRD had higher incidence than MUD (8.7 ± 3.0% vs 1.8 ± 1.2%, P = 0.012) and MSD (8.7 ± 3.0% vs 3.5 ± 2.6%, P = 0.004 ). The steroids combined with Cyclosporine A were acted as the first line treatment, and the response rate was 73%. No patients experienced recurrence at a median follow up of 313 days after stopping treatment. HRD transplants (vs MUD: HR, 5.87; CI, 1.24 to 27.73; p = 0.026 and vs MSD: HR, 7.70; CI, 1.63 to 36.44; P = 0.010) and concurrent chronic graft versus host disease (HR, 3.76; CI, 1.18 to 11.92; P = 0.025) were risk factors for AHDs.
[Mh] Termos MeSH primário: Doenças Autoimunes/terapia
Doenças Hematológicas/terapia
Transplante de Células-Tronco Hematopoéticas
Irmãos
Doadores não Relacionados
[Mh] Termos MeSH secundário: Adolescente
Adulto
Doenças Autoimunes/diagnóstico
Doenças Autoimunes/mortalidade
Feminino
Doença Enxerto-Hospedeiro/diagnóstico
Doença Enxerto-Hospedeiro/etiologia
Antígenos HLA/genética
Antígenos HLA/imunologia
Doenças Hematológicas/diagnóstico
Doenças Hematológicas/mortalidade
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Transplante de Células-Tronco Hematopoéticas/métodos
Teste de Histocompatibilidade
Seres Humanos
Incidência
Masculino
Meia-Idade
Transplante Homólogo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15710


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Registro de Ensaios Clínicos
[PMID]:29298160
[Au] Autor:Sullivan KM; Goldmuntz EA; Keyes-Elstein L; McSweeney PA; Pinckney A; Welch B; Mayes MD; Nash RA; Crofford LJ; Eggleston B; Castina S; Griffith LM; Goldstein JS; Wallace D; Craciunescu O; Khanna D; Folz RJ; Goldin J; St Clair EW; Seibold JR; Phillips K; Mineishi S; Simms RW; Ballen K; Wener MH; Georges GE; Heimfeld S; Hosing C; Forman S; Kafaja S; Silver RM; Griffing L; Storek J; LeClercq S; Brasington R; Csuka ME; Bredeson C; Keever-Taylor C; Domsic RT; Kahaleh MB; Medsger T; Furst DE; SCOT Study Investigators
[Ad] Endereço:From the Duke University Medical Center (K.M.S., O.C., E.W.S.C.) and RTI International (D.W.), Durham, and Rho Federal Systems Division, Chapel Hill (L.K.-E., A.P., B.E., S.C.) - all in North Carolina; National Institute of Allergy and Infectious Diseases, Bethesda, MD (E.A.G., B.W., L.M.G., J.S.G.)
[Ti] Título:Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.
[So] Source:N Engl J Med;378(1):35-47, 2018 01 04.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. RESULTS: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).
[Mh] Termos MeSH primário: Ciclofosfamida/uso terapêutico
Transplante de Células-Tronco Hematopoéticas
Imunossupressores/uso terapêutico
Escleroderma Sistêmico/terapia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Ciclofosfamida/efeitos adversos
Intervalo Livre de Doença
Feminino
Seguimentos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Transplante de Células-Tronco Hematopoéticas/mortalidade
Seres Humanos
Imunossupressores/efeitos adversos
Infecção/etiologia
Análise de Intenção de Tratamento
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Escleroderma Sistêmico/tratamento farmacológico
Escleroderma Sistêmico/mortalidade
Condicionamento Pré-Transplante
Transplante Autólogo
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 8N3DW7272P (Cyclophosphamide)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180304
[Lr] Data última revisão:
180304
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180104
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE



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