Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nature ; 568(7751): 244-248, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836379

RESUMO

A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago1,2. The individual-who is known as the 'Berlin patient'-underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin's lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression.


Assuntos
Infecções por HIV/terapia , Infecções por HIV/virologia , HIV-1 , Transplante de Células-Tronco Hematopoéticas/métodos , Receptores CCR5/química , Receptores CCR5/genética , Linfócitos T CD4-Positivos/imunologia , Citomegalovirus/química , Citomegalovirus/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/complicações , HIV-1/química , HIV-1/imunologia , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Humanos , Receptores CCR5/deficiência , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Transplante Homólogo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
2.
Biol Blood Marrow Transplant ; 26(3): 451-457, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31647984

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P= .016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P = .022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P< .0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias , Adulto , Medula Óssea , Comorbidade , Humanos , Estudos Retrospectivos , Condicionamento Pré-Transplante
3.
Biol Blood Marrow Transplant ; 25(3): 522-528, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30408564

RESUMO

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34+ cell dose was 4.8 × 106/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.


Assuntos
Família , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Mielofibrose Primária/terapia , Adulto , Idoso , Transplante de Medula Óssea/estatística & dados numéricos , Bases de Dados Factuais , Europa (Continente) , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Mielofibrose Primária/mortalidade , Recidiva , Estudos Retrospectivos , Sociedades Médicas , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo
5.
Curr Opin Oncol ; 30(6): 418-424, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30222641

RESUMO

PURPOSE OF REVIEW: To summarize the past and current knowledge of the use of unrelated donors (URDs) in allogeneic stem cell transplantation for patients with acute leukaemia. RECENT FINDINGS: The outcome of URD stem cell transplants in terms of treatment-related mortality, relapse rates, disease free survival and overall survival is comparable to sibling donors. SUMMARY: Haematopoietic stem cell transplantation (HSCT) is the therapy of choice in many haematological malignant diseases but only one-third of the patients will have an HLA-matched sibling. The possibility of finding a matched URD is more than 70% because of recent advances in HLA typing and continuous expansion of URD registries around the world. The use of URD as a source of stem cells in adult patients are steadily increasing and in the last 8 years, superseded the matched sibling donors and became the most commonly used stem cell source. There is also an increasing trend of using peripheral blood stem cells than bone marrow stem cells. Outcomes following URD transplants depend mainly upon the indication and urgency of transplant, age and comorbidities of recipients, cytomegalovirus matching/mismatching between donor and the recipient and degree of HLA matching.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Doadores não Relacionados , Doença Aguda , Antígenos HLA/imunologia , Humanos , Transplante Homólogo
6.
Cancer ; 123(15): 2875-2880, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28387926

RESUMO

BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported. RESULTS: After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]). CONCLUSIONS: Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875-80. © 2017 American Cancer Society.


Assuntos
Antineoplásicos/uso terapêutico , Crise Blástica/terapia , Imidazóis/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Piridazinas/uso terapêutico , Transplante de Células-Tronco/métodos , Adulto , Idoso , Crise Blástica/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento
7.
Br J Haematol ; 177(5): 759-765, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28369779

RESUMO

Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo
8.
Eur J Haematol ; 98(6): 632-634, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28083990

RESUMO

BACKGROUND: Haemorrhagic cystitis caused by BK virus (BKV) is a known complication of allogeneic haematopoietic cell transplantation (HCT) and is relatively common following HLA-haploidentical transplantation. Adoptive immunotransfer of virus-specific T cells from the donor is a promising therapeutic approach, although production of these cells is challenging, particularly when dealing with low-frequency T cells such as BKV-specific T cells. CASE REPORT: Here, we present a patient who, following haploidentical HCT, developed severe BKV haemorrhagic cystitis, resistant to standard therapy. He responded well to adoptive transfer of donor cells enriched in BKV-specific T cells using the new second-generation CliniMACS Prodigy and the Cytokine Capture System from Miltenyi Biotec. Treatment led to full resolution of both the symptoms and viraemia without unwanted complications. CONCLUSION: Our observations suggest that use of products enriched with BKV-specific T cells generated using this system is safe and efficient in HLA-haploidentical HCT where BKV cystitis can be a serious complication.


Assuntos
Cistite/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/terapia , Imunoterapia Adotiva , Infecções por Polyomavirus/terapia , Linfócitos T/transplante , Infecções Tumorais por Vírus/terapia , Adulto , Vírus BK/patogenicidade , Vírus BK/fisiologia , Cistite/etiologia , Cistite/imunologia , Cistite/patologia , Hemorragia/etiologia , Hemorragia/imunologia , Hemorragia/patologia , Teste de Histocompatibilidade , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Infecções por Polyomavirus/etiologia , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/patologia , Transplante Isogênico , Resultado do Tratamento , Infecções Tumorais por Vírus/etiologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/patologia
9.
Am J Hematol ; 92(11): 1214-1223, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28815757

RESUMO

Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted.


Assuntos
Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Padrões de Prática Médica , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Biópsia , Medula Óssea/patologia , Comorbidade , Europa (Continente) , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide de Fase Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento , Estados Unidos
10.
Transpl Infect Dis ; 19(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28921749

RESUMO

The use of preemptive antiviral therapy to prevent cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients might result in over-treatment, inducing drug-related toxicity and viral resistance. A search for predictive markers is needed to determine requirement for antiviral therapy. Clinical follow-up, in combination with the use of streptamers (STs) and cytokine-intracellular staining, could help to identify patients at high risk for CMV reactivations. To study the immune response and reactivation control by CMV-specific CD8+ T-cell (CMV-CTL) populations, we monitored 25 patients who have undergone allo-HSCT by using ST multimer and intracellular cytokine staining. Our study has revealed that the presence of functional CMV-specific T cells, determined by early interferon γ production or by significant T-cell expansion after first CMV reactivation, correlated with short CMV viremia duration and low number of CMV reactivations. By contrast, the absence of functional CMV-CTLs does correlate with CMV recurrence. These results support that behavior of CMV-specific subpopulations after reactivation influences reactivations and can guide preemptive therapy.


Assuntos
Antibioticoprofilaxia/efeitos adversos , Linfócitos T CD8-Positivos/virologia , Infecções por Citomegalovirus/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ativação Viral , Adulto , Antibioticoprofilaxia/métodos , Antivirais/efeitos adversos , Biomarcadores/sangue , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/isolamento & purificação , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Transplantados , Transplante Homólogo/efeitos adversos , Viremia/prevenção & controle
11.
Biol Blood Marrow Transplant ; 22(10): 1874-1882, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27397724

RESUMO

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft-versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy resultswere consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose.


Assuntos
Ensaios de Uso Compassivo , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Polidesoxirribonucleotídeos/administração & dosagem , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Progressão da Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/complicações , Hepatopatia Veno-Oclusiva/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Polidesoxirribonucleotídeos/efeitos adversos , Sepse/etiologia , Adulto Jovem
12.
N Engl J Med ; 369(5): 438-47, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23902483

RESUMO

BACKGROUND: For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention. METHODS: In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety. RESULTS: After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; P<0.001). The 3-year survival rate was also higher in the treatment group (94% vs. 80%; hazard ratio for death, 0.31; 95% CI, 0.10 to 0.91; P=0.03). A partial response or better was achieved in 79% of patients in the treatment group after the induction phase and in 90% during the maintenance phase. Toxic effects were mainly grade 2 or lower. CONCLUSIONS: Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Humanos , Quimioterapia de Indução , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Risco , Taxa de Sobrevida , Talidomida/efeitos adversos , Talidomida/uso terapêutico
13.
Ann Hematol ; 95(6): 967-72, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26994010

RESUMO

In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of these, 225 (98 %; 112 with, 113 without splenic irradiation) could be identified in the database and their survival updated. Results confirmed the early findings with no significant differences in all measured endpoints (overall survival at 25 years: 42.7 %, 32.0-52.4 % vs 52.9 %, 43.2-62.6 %; p = 0.355, log rank test). Additional splenic irradiation failed to reduce relapse incidence. It did not increase non-relapse mortality nor the risk of late secondary malignancies. Comforting are the long-term results from this predefined consecutive cohort of patients: more than 60 % were alive at plus 25 years when they were transplanted with a low European Society for Blood and Marrow Transplantation (EBMT) risk sore. This needs to be considered today when treatment options are discussed for patients who failed initial tyrosine kinase inhibitor therapy and have an available low risk HLA-identical donor.


Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/radioterapia , Baço/efeitos da radiação , Condicionamento Pré-Transplante/tendências , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Adulto Jovem
14.
Transfus Apher Sci ; 54(2): 248-52, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26345109

RESUMO

BACKGROUND AND OBJECTIVES: Platelets are stored routinely for 5 days or less and extended platelet storage time could improve product availability. This study compared platelet count increments (CI24hs) of riboflavin plus UV-light (PRT) treated platelet products in platelet additive solution stored for 5 days or less to products stored for 6-7 days. MATERIAL AND METHODS: This was a retrospective study comparing CI24hs between two groups. Hematology patients received PRT treated platelet products stored for <5 days, or for 6-7 days. Platelet counts and adverse events during and up to 24 hours after transfusion were recorded and compared between the groups. RESULTS: Ninety-seven patients received 168 transfusions of <5 day old PRT-treated platelets and 49 patients received 74 transfusions of 6-7 day old PRT-treated platelets. There was no statistically significant difference in CI24hs between the <5 day (median 6000) and 6-7 day storage group (median 8000) (p-value = 0.509). One mild fever was documented in the <5 day storage group. CONCLUSION: CI24hs are similar for PRT-treated PLTs stored in PAS for <5 or 6-7 days. Studies to further evaluate clinical outcomes such as bleeding are ongoing.


Assuntos
Plaquetas , Preservação de Sangue/métodos , Segurança do Sangue/métodos , Desinfecção/métodos , Transfusão de Plaquetas , Riboflavina/farmacologia , Raios Ultravioleta , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Riboflavina/química , Fatores de Tempo
15.
Cell Mol Life Sci ; 72(21): 4049-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26174234

RESUMO

Approximately, up to 70 % of the human population is infected with cytomegalovirus (CMV) that persists for life in a latent state. In healthy people, CMV reactivation induces the expansion of CMV-specific T cells up to 10 % of the entire T cell repertoire. On the contrary, CMV infection is a major opportunistic viral pathogen that remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Due to the delayed CMV-specific immune recovery, the incidence of CMV reactivation during post-transplant period is very high. Several methods are currently available for the monitoring of CMV-specific responses that help in clinical monitoring. In this review, essential aspects in the immune recovery against CMV are discussed to improve the better understanding of the immune system relying on CMV infection and, thereby, helping the avoidance of CMV disease or reactivation following hematopoietic stem cell transplantation with severe consequences for the transplanted patients.


Assuntos
Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/terapia , Citomegalovirus/patogenicidade , Transplante de Células-Tronco Hematopoéticas , Antivirais/farmacologia , Linfócitos T CD8-Positivos/virologia , Citocinas/metabolismo , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/prevenção & controle , Humanos , Hospedeiro Imunocomprometido/imunologia , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Polimorfismo Genético , Receptores CCR5/genética , Receptores CCR5/imunologia , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Ativação Viral
16.
J Clin Apher ; 31(1): 48-52, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26011178

RESUMO

Peripheral blood progenitor cells (PBPCs) have become the major source of hematopoietic progenitor cells for allogeneic transplantation. In February 2008, Zarzio® was approved by the European Medicine Agency for PBPCs mobilization, but this authorization was not based in trials analyzing safety and efficacy for PBPCs mobilization. Since August 2011, Zarzio® has been used at our institution for PBPCs mobilization. In total 36 healthy family donors underwent PBPCs mobilization, 18 with Neupogen® and 18 with Zarzio®. Donor characteristics were equivalent between groups, and no severe adverse effects were registered in the Zarzio® group. The number of CD34 cells collected/Kg recipient body weight was 6.7 × 10(6) (3.8-11.1) in the Zarzio® group versus 8.4 × 10(6) (5.6-16.6) in the Neupogen® group (P = 0.04). We collected the minimal target cell dose (2 × 10(6) /kg) in all donors from each group and no significant differences were found in the collection of the optimal cell dose (5 × 10(6) /kg) between groups, although 3/18 (16.6%) donors that received Zarzio® failed to mobilize the optimal cell dose compared with 0% in the Neupogen® group. A total of 35 patients proceeded to transplantation (17 in the Zarzio® and 18 in the Neupogen® groups, respectively). Platelet and neutrophil median time to engraftment was comparable between the two groups. Our retrospective study supports the conclusion that Zarzio® mobilization of PBPCs in healthy donors is safe but perhaps not as effective as the reference Neupogen. However, more prospective trials are required to definitively asses the safety and efficacy of G-CSF biosimilars for PBPCs mobilization in healthy donors.


Assuntos
Medicamentos Biossimilares/farmacologia , Filgrastim/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Contagem de Células , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Transplante Homólogo , Adulto Jovem
17.
Biol Blood Marrow Transplant ; 21(7): 1230-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25797175

RESUMO

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos , Condicionamento Pré-Transplante , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Imunossupressores/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores Sexuais , Irmãos , Análise de Sobrevida , Transplante Homólogo , Doadores não Relacionados
18.
J Transl Med ; 13: 165, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25990023

RESUMO

BACKGROUND: Adoptive transfer of CMV-specific T cells has shown promising results in preventing pathological effects caused by opportunistic CMV infection in immunocompromised patients following allogeneic hematopoietic stem cell transplantation. The majority of studies have used steady-state leukapheresis for CMV-reactive product manufacture, a collection obtained prior to or months after G-CSF mobilization, but the procurement of this additional sample is often not available in the unrelated donor setting. If the cellular product for adoptive immunotherapy could be generated from the same G-CSF mobilized collection, the problems associated with the additional harvest could be overcome. Despite the tolerogenic effects associated with G-CSF mobilization, recent studies described that CMV-primed T cells generated from mobilized donors remain functional. METHODS: MHC-multimers are potent tools that allow the rapid production of antigen-specific CTLs. Therefore, in the present study we have assessed the feasibility and efficacy of CMV-specific CTL manufacture from G-CSF mobilized apheresis using MHC-multimers. RESULTS: CMV-specific CTLs can be efficiently isolated from G-CSF mobilized samples with Streptamers and are able to express activation markers and produce cytokines in response to antigenic stimulation. However, this anti-viral functionality is moderately reduced when compared to non-mobilized products. CONCLUSIONS: The translation of Streptamer technology for the isolation of anti-viral CTLs from G-CSF mobilized PBMCs into clinical practice would widen the number of patients that could benefit from this therapeutic strategy, although our results need to be taken into consideration before the infusion of antigen-specific T cells obtained from G-CSF mobilized samples.


Assuntos
Citomegalovirus/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Antígenos HLA/metabolismo , Mobilização de Células-Tronco Hematopoéticas , Multimerização Proteica , Linfócitos T Citotóxicos/imunologia , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Citocinas/metabolismo , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Granzimas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Peptídeos/imunologia , Fenótipo , Especificidade da Espécie , Linfócitos T Citotóxicos/efeitos dos fármacos
19.
Blood ; 122(24): 3863-70, 2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24065243

RESUMO

Cyclophosphamide combined with total body irradiation (Cy/TBI) or busulfan (BuCy) are the most widely used myeloablative conditioning regimens for allotransplants. Recent data regarding their comparative effectiveness are lacking. We analyzed data from the Center for International Blood and Marrow Transplant Research for 1230 subjects receiving a first hematopoietic cell transplant from a human leukocyte antigen-matched sibling or from an unrelated donor during the years 2000 to 2006 for acute myeloid leukemia (AML) in first complete remission (CR) after conditioning with Cy/TBI or oral or intravenous (IV) BuCy. Multivariate analysis showed significantly less nonrelapse mortality (relative risk [RR] = 0.58; 95% confidence interval [CI]: 0.39-0.86; P = .007), and relapse after, but not before, 1 year posttransplant (RR = 0.23; 95% CI: 0.08-0.65; P = .006), and better leukemia-free survival (RR = 0.70; 95% CI: 0.55-0.88; P = .003) and survival (RR = 0.68; 95% CI: 0.52-0.88; P = .003) in persons receiving IV, but not oral, Bu compared with TBI. In combination with Cy, IV Bu is associated with superior outcomes compared with TBI in patients with AML in first CR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide/terapia , Irradiação Corporal Total , Doença Aguda , Adolescente , Adulto , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Indução de Remissão , Irmãos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
20.
Cell Mol Life Sci ; 71(7): 1211-24, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24077876

RESUMO

Chemotherapy and/or radiotherapy regular regimens used for conditioning of recipients of hematopoietic stem cell transplantation (SCT) induce a period of transient profound immunosuppression. The onset of a competent immunological response, such as the appearance of viral-specific T cells, is associated with a lower incidence of viral infections after haematopoietic transplantation. The rapid development of immunodominant peptide virus screening together with advances in the design of genetic and non-genetic viral- and tumoural-specific cellular selection strategies have opened new strategies for cellular immunotherapy in oncologic recipients who are highly sensitive to viral infections. However, the rapid development of cellular immunotherapy in SCT has disclosed the role of the T cell selection method in the modulation of functional cell activity and of in vivo secondary effects triggered following immunotherapy.


Assuntos
Imunoterapia Adotiva/métodos , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Suscetibilidade a Doenças , Transplante de Células-Tronco Hematopoéticas , Humanos , Terapia de Imunossupressão , Modelos Imunológicos , Viroses/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA