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1.
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
2.
N Engl J Med ; 381(12): 1136-1147, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532960

RESUMO

BACKGROUND: Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known. METHODS: In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment. RESULTS: Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir. CONCLUSIONS: Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/fisiologia , Ribonucleosídeos/uso terapêutico , Valganciclovir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Idoso , Aloenxertos , Antivirais/efeitos adversos , Antivirais/farmacologia , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacologia , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/virologia , Disgeusia/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Transplante de Órgãos/efeitos adversos , Ribonucleosídeos/efeitos adversos , Ribonucleosídeos/farmacologia , Valganciclovir/efeitos adversos , Valganciclovir/farmacologia , Ativação Viral/efeitos dos fármacos
3.
Bratisl Lek Listy ; 120(9): 668-672, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475551

RESUMO

Restrospective study to evaluate the efficacy of early vs. delayed initiation of G-CSF after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoid malignancies. BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is commonly used after AHSCT to accelerate stem cell engraftment to minimize the morbidity and mortality associated with prolonged neutropenia. However, there is no consensus on the optimal timing of G-CSF after HSCT. METHODS: A total of 117 patients with lymphoid malignancies who underwent AHSCT were included. All patients received G-CSF (filgrastim 5 µg/kg s.c.) daily after AHSCT (43 patients on day 6-8 and 74 patients on day 3 or 4). All patients received standard conditioning regimen for the underlying disease, and standard supportive treatment, including treatment of febrile neutropenia. RESULTS: The incidence of severe neutropenia was 81 % vs 17 %, and very severe neutropenia 61 % vs 4 % in the delayed and early G-CSF groups, respectively (p < 0.0001). The rate of fungal infection was higher in the group of patients who received delayed G-CSF (p < 0.005). CONCLUSION: An early administration of G-CSF after AHSCT (on day 3 or 4) accelerates neutophil engraftment; decreases the incidence of severe neutropenia and the risk of infectious complications (especially fungal infections) (Tab. 1, Fig. 3, Ref. 22).


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Filgrastim/administração & dosagem , Humanos , Neutropenia/terapia , Neutrófilos/citologia , Proteínas Recombinantes/administração & dosagem , Condicionamento Pré-Transplante , Transplante Autólogo
4.
N Engl J Med ; 381(13): 1240-1247, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31509667

RESUMO

The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.).


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Infecções por HIV/terapia , HIV-1 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Receptores CCR5/genética , Adulto , Antirretrovirais/uso terapêutico , Contagem de Células Sanguíneas , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Carga Viral
5.
Rinsho Ketsueki ; 60(8): 953-959, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484895

RESUMO

Graft-versus-host-disease (GvHD) is a major complication and leading cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Corticosteroids remain the standard initial therapy for GvHD; however, patients frequently become steroid-refractory (SR) or remain steroid dependent. Cytokine inhibition appears to be a potential option; however, blockade of any single cytokine may not be sufficient probably because of the redundant effects of multiple cytokines. The Jak1/2 inhibitor ruxolitinib can simultaneously inhibit the signaling pathway of multiple cytokines with relevance for GvHD, such as interferon (IFN-γ), IL-2, and IL-6. A recent retrospective survey reported that ruxolitinib produced a high response rate for SR-GvHD, leading to better survival odds. A prompt and sustained ruxolitinib response contributes to the steroid-sparing effect; however, accumulating evidence showed that ruxolitinib exerts substantial myelosuppression and immunosuppressive activity in patients with myelofibrosis (MF). Additionally, serious adverse events following discontinuation of ruxolitinib treatment, characterized by acute relapse of the disease and/or GvHD, have been recognized. Herein we discuss the advantages and disadvantages of ruxolitinib as treatment for GvHD in patients with MF.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Pirazóis/uso terapêutico , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Mielofibrose Primária/complicações , Estudos Retrospectivos
6.
Rinsho Ketsueki ; 60(8): 960-967, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484896

RESUMO

Myelodysplastic syndromes (MDS) constitute a group of heterogeneous disorders of hematopoietic stem cells, characterized by defective hematopoiesis and multilineage dysplasia. While low-risk subtypes normally exhibit a relatively chronic clinical course, high-risk subtypes harbor unfavorable prognosis in which hematopoietic stem cell transplantation (HCT) is the only curative therapy. Nevertheless, transplantation-related mortality is relatively high and should be weighed against the potential benefits of HCT. Hence, it is vital to precisely stratify the prognostic risks before HCT for predicting and enhancing their prognosis. Recently, our understanding of the genetic basis of MDS has substantially advanced, through which a full spectrum of major mutational targets was delineated. Moreover, its effects in the setting of HCT have also been assessed besides the conventional predictive factors. While clinical factors account for as much as 70% of the total hazard of MDS cases treated with HCT, the remaining 30% is explicated by genetic factors. The integration of genetic test and conventional clinical factors could be useful for precise stratification of the prognostic risks and, therefore, treatment decision in MDS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Mutação , Prognóstico , Transplante de Células-Tronco
7.
Rinsho Ketsueki ; 60(8): 968-972, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484897

RESUMO

Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Patients with aggressive ATL exhibit poor outcomes, even with dose-dense intensive chemotherapy. Thus, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered in all patients eligible for transplant. However, patients with aggressive ATL often have chemo-refractoriness or experience early relapse during chemotherapy. Allo-HSCT is often ineffective in patients with active disease status. Mogamulizumab (Moga) was approved in 2012 in Japan as a potent treatment option for patients with relapsed or refractory ATL. However, there is a major concern that the use of Moga before allo-HSCT could increase the risk of post-transplant complications, such as graft-versus-host disease (GVHD), because Moga depletes regulatory T cells. Here, we would like to describe the possible effects of pre-transplant Moga on post-transplant complications, such as acute GVHD, and to discuss how Moga could be efficiently incorporated in the treatment regimen of patients with aggressive ATL to maximize the expected clinical benefit.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Adulto , Humanos , Japão , Receptores CCR4 , Transplante Homólogo
8.
Rinsho Ketsueki ; 60(8): 979-987, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484899

RESUMO

POEMS syndrome is a rare paraneoplastic disorder characterized by polyneuropathy, organomegaly, endocrinopathy, λ-type monoclonal protein derived from only two germlines (IGLV1-40 or IGLV1-44), skin changes, extravascular volume overload, and serum vascular endothelial growth factor elevation. To understand the molecular pathophysiology of the disease, comprehensive genetic analyses of bone marrow plasma cells was performed in 20 patients with the syndrome. Although a median of 14.5 mutated genes were identified per patient, none of the driver gene mutations frequently found in multiple myeloma were detected. RNA sequencing revealed a transcription profile specific to POEMS syndrome, which suggested that the genetic and transcriptional profiles of plasma cells in POEMS syndrome are distinct from multiple myeloma and monoclonal gammopathy of undetermined significance. Treatment strategies for the devastating disease have been developed by targeting monoclonal plasma cells with novel agents, mainly thalidomide, followed by autologous stem cell transplantation (ASCT). Moreover, the 5-year overall survival after ASCT has improved to as high as 90% with dramatic improvement in symptoms and activities of daily living. However, the 5-year progression-free survival during long-term follow-up has dropped to 60%. Therefore, identifying novel therapeutic targets are imperative for further improvement of disease outcomes.


Assuntos
Síndrome POEMS , Atividades Cotidianas , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Autólogo , Fator A de Crescimento do Endotélio Vascular
9.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 650-655, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495131

RESUMO

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Quimerismo , Humanos , Imunoterapia Adotiva , Linfócitos T
10.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 662-666, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495133

RESUMO

Objective: To establish a new method for chimerism analysis after allogeneic hematopoietic stem cell transplantation by using multiple nucleotide polymorphism sequencing (MNPseq) , and to explore its feasibility and superiority. Methods: One hundred MNP fragments were screened and chimeric analysis was performed by high-throughput sequencing technology. The accuracy and sensitivity of the method were verified by simulating chimeric samples and post-transplant samples and comparing them with short tandem repeat (STR) analysis, fusion gene quantitative detection and flow cytometry for minimal residual disease. Results: The accuracy and sensitivity of MNPseq were better than those of STR, in which the sensitivity could reach 0.01%, about 100 times more sensitive than STR. MNPseq could further distinguish 42 STR fully chimeric samples, and after corrected by cutoff value, it was correlated with the quantitative detection of fusion gene. MNPseq could correct false positive of STR caused by the shadow peak, and could be used to detect chimeric samples lacking pre-transplant information from donors and recipients. Conclusion: MNPseq analysis based on high-throughput sequencing is a more accurate and sensitive chimerism detection method, and it solves the problem that chimerism cannot be detected due to the lack of pre-transplant information, which has extremely high clinical application value.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Humanos , Polimorfismo Genético , Doadores de Tecidos , Quimeras de Transplante
11.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 667-672, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495134

RESUMO

Objective: To analyze the efficacy of HLA-haploidentical peripheral hematopoietic stem cell transplantation (haplo-PBSCT) following reduced intensity conditioning (RIC) regimen to treat the patients with hematological malignancies who were older than 50 years old. Methods: Eighteen patients with hematological malignancies over 50 years were enrolled, including 8 male and 10 female patients. The median age of all patients was 52 (range: 50-66) years. Of them, 8 patients had acute myeloid leukemia (AML) , 2 chronic myelocytic leukemia (CML) , 5 myelodysplastic syndrome (MDS) , 2 acute lymphoblastic leukemia (ALL) , and 1 aggressive natural killer cell leukemia (ANKL) . All patients received fludarabine, cytarabine and melphalan with rabbit anti-human thymocyte globulin (FAB+rATG regimen) and transplanted with high dose non-T cell-depleted peripheral hematopoietic stem cells from donors. Enhanced graft versus host disease (GVHD) prophylaxis and infection prevention were administered. Results: Fifteen days after transplantation, 16 patients achieved complete donor chimerism. One of them rejected the donor graft completely at thirty days after transplantation, and the other 2 patients had mixed chimerism 15 days after transplantation and converted to complete recipient chimerism at 30 days after transplantation. The cumulative incidence of acute GVHD (aGVHD) was 61.1% (95%CI49.6%-72.6%) . The incidence of grade Ⅱ-Ⅳ aGVHD was 35.4% (95%CI 21.1%-49.7%) , whereas grade III-IV was 13.8% (95%CI 4.7%-22.9%) . The 2-year cumulative incidence of chronic GVHD (cGVHD) rate was estimated at 38.2% (95%CI 25.5%-50.9%) . Patients were followed-up for a median of 14.5 months (range, 3-44 months) . The Kaplan Meier estimates of 2-year overall survival (OS) and disease-free survival (DFS) was 72.6% (95%CI 60.1%-85.1%) and 63.7% (95%CI 49.2%-78.2%) , respectively. The 2-year cumulative incidence of relapse and non-relapse-mortality (NRM) was 31.2% (95%CI 16.5%-45.9%) and 12.5% (95%CI 4.2%-20.8%) , respectively. Conclusion: RIC-haplo-PBSCT protocol can achieve better results in patients with hematologic malignancies over 50 years old.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(8): 923-929, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31511212

RESUMO

We analyzed the clinicopathological data of 3 cases of primary intraosseous hematopoietic pseudotumor (IHPT), which had been previously misdiagnosed as malignancies or metastases both clinically and pathologically. Two of the patients received close follow-up for 132 and 100 months, and one patient was lost to follow-up, and the tumors were confirmed to be benign in all the 3 cases. IHPT is a rare benign intraosseous solid lesion consisting of tissues resembling normal hematopoietic tissue, and can be easily misdiagnosed as malignancy. Understanding the clinicopathological features and the outcomes of the disease can facilitate the clinical decisions on individualized diagnosis and therapeutic regimens.


Assuntos
Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Seguimentos , Humanos
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 485-491, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484610

RESUMO

To analyze the treatment and prognosis of T cell acute lymphoblastic leukemia(T-ALL)in adults. Method The clinicobiogical and survival data of 68 adult patients with newly diagnosis T-ALL were retrospectively analzyed. Results The median age of these 68 patients was 23 years(14-60 years).T-ALL was more common in men(81%).After the first cycle of treatment,complete remission was achieved in 50 patients(73%).The highest complete remission(CR) rate was in patients with cortex T-ALL(100%),followed by other T-ALL(73%)and early T-cell precursor lymphoblastic leukemia(54%),(χ 2=5.712,P=0.058).The CR rate for adults aged >35 years was significantly lower than that of patients aged ≤ 35 years(40% vs. 79%,χ 2=6.364,P=0.012).The overall CR rate after the second treatment course was 93%.For patients treated with chemotherapy,autograft hematopoietic stem cell transplantation(auto-SCT),and allogeneic SCT,the median relapse free survival was 10 months,24 months,and not reached,respectively(P=0.002).The 5-year overall survival rate was 25% for all patients;for patients treated with chemotherapy,auto-SCT and allogeneic SCT,the median overall survival was 24 months,34 months,and 30 months,respectively(P=0.007),and the 5-year overall survival rate was 9%,33%,and 38%(P=0.037).Multivariate analysis showed leukocyte count ≥100×10 9/L was a risk factor for decreased relapse free survival(risk ratio 2.540,95%CI=1.058-6.099,P=0.037). Conclusion Adult T-ALL patients have poor prognosis,which may be improved by SCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
BMJ Open ; 7(1): [10], Aug. 28, 2019.
Artigo em Inglês | BIGG | ID: biblio-1010328

RESUMO

To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT). The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations. We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children. All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted.


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Fototerapia/métodos , Estomatite/prevenção & controle , Doenças Faríngeas/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Mucosite , Neoplasias/terapia
15.
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
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1040-1045, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418354

RESUMO

OBJECTIVE: To study the long-term efficacy and safety of CD19 chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed patients with B-cell acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 7 patients with B-cell ALL relapsed after allo-HSCT were treated with CD19 CAR-T cells from September 2015 to March 2018. Among them, 6 had hematological recurrence and 1 had positive of MRD. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 6.0 (range 4.0-8.6) )×106/kg. Long-term efficacy and toxicity were evaluated. RESULTS: Bone marrow examination performed at d 30 after CAR-T infusion showed that all 7 patients achieved complete remission and MRD negative, grade I CRS for 1 case and grade II CRS for 6 cases, two of them had mild neurotoxicity, which was controlled by treatment. Two patients presented grade VI intestinal GVHD after CAR-T infusion. The median follow-up time was 18 months (range 12-42). Follow-up showed that two patients relapsed at 9 months and 14 months after treatment, out of 2 patients one died of progressive disease and the other reachived the hematological remission, but MRD was positive after CD22 CAR-T cell therapy. At present, five patients are disease-free survival, moreover showed complete donor chimerism. One year after CAR-T cell therapy, the results of immune reconstitution showed that CD4 level was more than 300×106/L in 5 patients who disease-free survived. Among them, 3 patients had poor recovery of immunoglobulin and received gamma globulin replacement therapy. CONCLUSION: All patients are followed up for at least one year. The preliminary efficacy and safety are satisfactory. CAR-T cell infusion is an effective method for the treatment of B-ALL recurrence after allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos B , Humanos , Receptores de Antígenos Quiméricos , Linfócitos T
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1138-1142, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418369

RESUMO

OBJECTIVE: To investigate the clinical efficacy of R-EDOCH protocol in the treatment of newly diagnosed double expression lymphoma. METHODS: The clinical data of 51 patients with newly diagnosed double expression lymphoma treated by R-EDOCH protocol were retrospectively analyzed in the period from May 2012 to October 2017, then overall remission rate (ORR), disease control rate (DCR), progression-free survival (PFS) rate and total survival (OS) rate were evaluated; moreover the patients were grouped according to IPI score and whether accepting hematopoietic stem cell transplantation(HSCT) and the clinical efficacy was compared. RESULTS: The ORR was 96.08% (49/51) and DCR was 100.00% (51/51) in all patients. Six cases out of 51 patients (11.76%) relapsed and progressed during the followed-up. The followed-up showed that 2 year-PFS rate and OS rate were 84.31% (43/51) and 94.12% (48/51) respectively. The ORR, SD rate, 2 year-PFS rate and OS rate in the patients with IPI 0-2 and 3-5 scores were no statistically different(p>0.05); the 2 year-PFS and OS rates between patients in subgroup of IPI 0-2 and 3-5 scores also were not statistically different (p>0.05), no matter whether the patients received auto-HSCT or not. The comparison of 2 year-PFS and OS rates in auto-HSCT patients and non-auto-HSCT patients showed no statistical difference(p>0.05). CONCLUSION: The R-EDOCH protocol in treatment of newly diagnosed double expression lymphoma possess the good overall clinical efficacy, the combination of R-EDOCH with auto-HSCT displays ascending trend of PFS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma Difuso de Grandes Células B , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1325-1329, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418401

RESUMO

Abstract  The curative efficacy of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has been improved substantially with the introduction of tyrosine kinase inhibitors (TKIs). However, there is no consensus so far on the following issues, which TKIs should be chosen in combination with chemotherapeutic regimens; which regimen of intensive chemotherapy incorporated into TKIs would be more beneficial to patients. The prognosis of the patients with Ph+ ALL has been so significantly improved by the combinatorial treatment of TKIs and chemotherapy, thus it is necessary to reevaluate the role of allogeneic hematopoietic stem cell transplantation in the management of Ph+ ALL. In addition, immunotherapy has achieved an initial success in the treatment of Ph+ ALL. In this review, the treatment paradigms for the disease are summrized briefly.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Cromossomos , Humanos , Cromossomo Filadélfia , Prognóstico , Inibidores de Proteínas Quinases
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1330-1333, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418402

RESUMO

Abstract  Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, high risk of transformation from MDS into AML. Allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, but the failure rate of transplantation is still high, which attribute to relapsed disease and transplant-related complications. Recently, the spectrum of gene abnormalities in MDS has been revealed by next generation genomic sequencing techniques. It was found that more than 80% MDS patients have at least one gene mutation. Mutated genes in MDS are powerfully associated with clinical phenotype and prognosis. In this review , the recent advancements regarding recurrent gene mutations in MDS are briefly summarized, and the  prognostic values of gene mutations are discussed in MDS or after allogeneic hematopoietic stem-cell transplantation,so as to set up a predicting model and to guide the treatment.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Mutação , Prognóstico , Transplante de Células-Tronco
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1334-1338, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418403

RESUMO

Abstract  At present, allogeneic hematopoietic stem cell transplantation is still the only way to cure chronic myelogenous leukemia. With the advances of HLA matching technology, application of tyrosine kinase inhibitors before and after transplantation, improvement of postoperative immune status and fusion gene monitoring, and the control of postoperative complications, especially graft-versus-host disease etc. allogeneic hematopoietic stem cell transplantation is displaying better efficacy in the treatment of chronic myelogenous leukemia, and the quality of life of patients has also been significantly improved. This article reviews the recent research advances on the allogeneic hematopoietic stem cell transplantation and related support technologies for treatment of chronic myeloid leukemia.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Qualidade de Vida , Transplante Homólogo
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