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1.
Blood ; 117(7): 2121-8, 2011 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-21163927

RESUMO

The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 µg) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/µL), medium (quartile 2; leukocytes > 10 100-18 300/µL), and high (quartiles 3/4; leukocytes > 18 300-44 800/µL). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P = .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P = .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P = .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials.gov as NCT01085058.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos , Infecções/etiologia , Linfoma/complicações , Linfoma/tratamento farmacológico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Infecções/sangue , Lenograstim , Linfoma/sangue , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Análise Multivariada , Neutropenia/sangue , Neutropenia/etiologia , Transplante de Células-Tronco de Sangue Periférico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes , Fatores de Risco , Adulto Jovem
2.
J Clin Oncol ; 28(30): 4642-8, 2010 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-20805454

RESUMO

PURPOSE: To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. PATIENTS AND METHODS: Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. RESULTS: Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. CONCLUSION: Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/cirurgia , Doadores de Tecidos/provisão & distribuição , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Áustria , Quimioterapia Adjuvante , Análise Citogenética , Alemanha , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Terapia Neoadjuvante , Linhagem , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
3.
Br J Haematol ; 126(4): 527-35, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15287946

RESUMO

The present study investigated the effects of CD34(+) cell selection in 102 patients using the CliniMACS device. Patients were at high risk for the development of graft versus host disease (GvHD) because of age, or the use of a haploidentical, mismatched or unrelated donor (UD). The median age of the patients was 44 years. The CliniMACS procedure yielded 8.0 x 10(6) CD34(+) cells/kg and the number of residual T cells was 1.3 x 10(4)/kg (median). The median follow up was 20.6 months. The probability of graft failure was 7%. The rate of acute GvHD was low (compatible family donors 10%, UDs 17%, and haploidentical donors 26%) with no patient enduring more than grade II disease. The cumulative incidence of chronic GvHD at the median follow up after transplant was 15% for the compatible family donor group, 40% for the UD group and 78% in the group transplanted from a haploidentical donor Treatment failure was mainly because of transplant-related mortality, especially aspergillus infection, and not due to relapse. The probability of disease-free survival, stratified for the risk of treatment failure, was 27% for the high risk, 46% for the intermediate risk and 83% for the low risk group.


Assuntos
Antígenos CD34/sangue , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Coleta de Tecidos e Órgãos/métodos , Doença Aguda , Adolescente , Adulto , Separação Celular/métodos , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Análise de Sobrevida , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos
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