Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
BMC Cancer ; 24(1): 272, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408958

RESUMO

BACKGROUND: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS: A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS: In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION: In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Gencitabina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Cloridrato de Erlotinib/uso terapêutico , Adenocarcinoma/patologia , Desoxicitidina , Fluoruracila , Leucovorina/uso terapêutico , Paclitaxel , Albuminas
4.
Bone Marrow Transplant ; 41(6): 555-62, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18037940

RESUMO

Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)). Patients with objective response (N=179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem cell support (N=88), or no further treatment (N=91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P=0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Análise de Sobrevida , Tiotepa/administração & dosagem , Transplante Autólogo , Resultado do Tratamento
5.
Arterioscler Thromb Vasc Biol ; 26(11): 2567-73, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16917107

RESUMO

OBJECTIVE: Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. METHODS AND RESULTS: Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (P<0.05). Fibrin of young CAD patients was stiffer (P=0.002), made of numerous (P=0.002) and shorter fibers (P=0.04), and lysed at a slower rate than that of controls (P=0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. CONCLUSIONS: This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. The determinants of this particular phenotype warrant further investigation.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Trombose Coronária/fisiopatologia , Fibrina/química , Fibrina/ultraestrutura , Fibrinólise , Adulto , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Trombose Coronária/sangue , Trombose Coronária/complicações , Elasticidade , Feminino , Fibrina/metabolismo , Fibrinogênio/metabolismo , Humanos , Lipoproteína(a)/sangue , Masculino , Microscopia Confocal , Infarto do Miocárdio/etiologia , Inibidor 1 de Ativador de Plasminogênio/sangue , Valor Preditivo dos Testes , Viscosidade , Fator de von Willebrand/metabolismo
6.
Circulation ; 110(16): 2361-7, 2004 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-15477397

RESUMO

BACKGROUND: Oral antiplatelet agents (OAAs) can prevent further vascular events in cardiovascular disease. How prior use or recent discontinuation of OAA affects clinical presentation of acute coronary syndromes (ACS) and clinical outcomes (death, myocardial infarction [MI]) is unclear. METHODS AND RESULTS: We studied and followed up for up to 30 days a cohort of 1358 consecutive patients admitted for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA, and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently presented with ST-elevation MI on admission, and more frequently had Q-wave MI at discharge than prior users (36.6% versus 17.5%, P<0.001; and 47.8% versus 28.2%, P<0.001, respectively). However, there was no difference regarding the incidence of death or MI at 30 days between nonusers and prior users (10.3% versus 12.4%, P=NS). In addition, prior users experienced more major bleeds within 30 days compared with nonusers (3.4% versus 1.4%, respectively; P=0.04). Recent withdrawers were admitted on average 11.9+/-0.8 days after OAA withdrawal. Interruption was primarily a physician decision for scheduled surgery (n=47 of 73). Despite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P=0.04) and bleedings (13.7% versus 5.9%, P=0.03) than prior users. After multivariate analysis, OAA withdrawal was found to be an independent predictor of both mortality and bleedings at 30 days. CONCLUSIONS: Among ACS patients, prior users represent a higher-risk population and present more frequently with non-ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.


Assuntos
Isquemia Miocárdica/etiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Suspensão de Tratamento , Doença Aguda , Administração Oral , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Eletrocardiografia , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Isquemia Miocárdica/epidemiologia , Paris/epidemiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Síndrome , Trombose/prevenção & controle , Resultado do Tratamento
7.
Circulation ; 110(4): 392-8, 2004 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-15249498

RESUMO

BACKGROUND: Low-molecular-weight heparin (LMWH) is recommended in the treatment of unstable angina (UA)/non-ST-segment-elevation myocardial infarction (NSTEMI), but no relationship has ever been shown between anticoagulation levels obtained with LMWH treatment and clinical outcomes. METHODS AND RESULTS: In all, 803 consecutive patients with UA/NSTEMI were treated with subcutaneous enoxaparin and were followed up for 30 days. The recommended dose of enoxaparin of 1 mg/kg BID was used throughout the population except when physicians decided on dose reduction because of a history of a recent bleeding event or because of a high bleeding risk. Anti-factor Xa activity was >0.5 IU/mL in 93% of patients; subtherapeutic anti-Xa levels (<0.5 IU/mL) were associated with lower doses of enoxaparin. The 30-day mortality rate was significantly associated with low anti-Xa levels (<0.5 IU/mL), with a >3-fold increase in mortality compared with the patients with anti-Xa levels in the target range of 0.5 to 1.2 IU/mL (P=0.004). Multivariate analysis revealed low anti-Xa activity as an independent predictor of 30-day mortality at least as strong as age, left ventricular function, and renal function. In contrast, anti-Xa activity did not predict major bleeding complications within the range of anti-Xa levels observed in this study. CONCLUSIONS: In this large unselected cohort of patients with UA/NSTEMI patients, low anti-Xa activity on enoxaparin treatment is independently associated with 30-day mortality, which highlights the need for achieving at least the minimum prescribed anti-Xa level of 0.5 IU/mL with enoxaparin whenever possible.


Assuntos
Angina Instável/tratamento farmacológico , Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Inibidores do Fator Xa , Infarto do Miocárdio/tratamento farmacológico , Ticlopidina/análogos & derivados , Idoso , Angina Instável/sangue , Angina Instável/mortalidade , Angina Instável/terapia , Angioplastia Coronária com Balão , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Biomarcadores , Cateterismo Cardíaco , Clopidogrel , Estudos de Coortes , Terapia Combinada , Creatina Quinase/sangue , Creatina Quinase Forma MB , Quimioterapia Combinada , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Enoxaparina/farmacologia , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Estudos Prospectivos , Análise de Sobrevida , Ticlopidina/administração & dosagem , Ticlopidina/uso terapêutico , Resultado do Tratamento , Troponina I/sangue
8.
Am Heart J ; 147(4): 655-61, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15077081

RESUMO

BACKGROUND: Subcutaneous enoxaparin during at least 48 hours provides adequate anticoagulation and good clinical results in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). METHODS: In this nonrandomized retrospective study, we compared 347 patients with non-ST-segment elevation acute coronary syndromes who underwent rapid PCI after only 2 injections of subcutaneous enoxaparin (EI, n = 117) to those referred later to the catheterization laboratory with >or=3 injections (DI, n = 230). We measured anti-Xa at the time of PCI and evaluated bleeding and major ischemic events (death/myocardial infarction) at 30 days. RESULTS: Patients in the EI group more frequently received glycoprotein IIb/IIIa inhibitors and clopidogrel preceding PCI than did patients in the DI group (58.1% vs 31.7%, P <.0001 for glycoprotein IIb/IIIa inhibitors and 68.4% vs 40.4% for clopidogrel pretreatment, P <.0001, respectively). The anti-Xa activity measured at the time of catheterization (0.92 +/- 0.04 U/mL vs 0.96 +/- 0.02 U/mL, EI vs DI, P =.25) and the injection-to-catheterization times (5.6 +/- 0.2 h vs 5.2 +/- 0.1 h, EI vs DI, P =.17) were similar in both groups. The 30-day bleeding rates of 1.7% and 4.8% in the EI and DI strategies were found to be equivalent with a significant non-inferiority test for the EI strategy (P <.05). There was a nonsignificant trend for less death or myocardial infarction at 30 days in the EI group compared to the DI group (4.3% vs 7.0%, non-inferiority test not significant). CONCLUSION: A rapid invasive strategy with only 2 subcutaneous injections of enoxaparin provides similar levels of anticoagulation, and is associated with a favorable trend for ischemic events and with safety equivalent to a more prolonged "upstream" treatment with enoxaparin.


Assuntos
Angina Instável/terapia , Angioplastia Coronária com Balão , Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Infarto do Miocárdio/terapia , Pré-Medicação , Ticlopidina/análogos & derivados , Análise de Variância , Angina Instável/mortalidade , Angioplastia Coronária com Balão/efeitos adversos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Cateterismo Cardíaco , Clopidogrel , Esquema de Medicação , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Injeções Subcutâneas , Modelos Logísticos , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/etiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Pré-Medicação/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Ticlopidina/uso terapêutico
9.
Neurology ; 60(11): 1820-2, 2003 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-12796538

RESUMO

An inhibitor of telomerase activity maps to chromosome 10p15.1. A series of 51 high-grade gliomas was analyzed for loss of heterozygosity (LOH) on chromosome 10 and for telomerase activity. In univariate analysis, LOH10p (59%) and LOH10q (61%) were associated with telomerase activity (55%; p < 0.0001 and p = 0.0006). In multivariate analysis, only LOH10p remained statistically related to telomerase activity, suggesting that the telomerase repressor gene located on 10p15.1 is inactivated in high-grade gliomas.


Assuntos
Cromossomos Humanos Par 10 , Glioma/genética , Perda de Heterozigosidade , Telomerase/metabolismo , Mapeamento Cromossômico , Glioma/enzimologia , Humanos
10.
Bone Marrow Transplant ; 31(10): 909-18, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12748668

RESUMO

SUMMARY: Philadelphia chromosome (Ph) acute lymphoblastic leukemia-positive (ALL) is a subgroup of ALL with a poor prognosis. We sought to evaluate the results of allogeneic hematopoietic stem cell transplantation (HSCT) in this situation. From 1992 to 2000, 121 patients with Ph- positive ALL enrolled in one of the three main French prospective ALL chemotherapy trials and receiving allogeneic HSCT were reported to the registry of the French Society of Bone Marrow Transplantation (SFGM-TC). The median age was 35 years (range, 1-53). In all, 76 patients received HSCT in first complete remission and 45 in a more advanced disease stage. Minimal residual disease was evaluated just before the graft: 35 patients of the 52 patients in first remission had persistent BCR-ABL transcript detectable while 17 had no detectable minimal residual disease. Bone marrow and/or peripheral blood samples from 94 patients were submitted for reverse transcriptase polymerase chain reaction analysis at variable points after transplantation. Estimated 2-year survival and relapse rate for patients in CR1 were 50 and 37%, respectively, significantly better than for patients with more advanced disease (P=0.0001 and 0.01, respectively). There was no difference in survival or in relapse rates in terms of the donor used. Relapse was the most common cause of treatment failure. Hematological status at the time of transplant and the occurrence of acute graft-versus-host disease (GvHD) were the only two prognostic factors identified for relapse (P=0.02 and 0.02, respectively). Detection of BCR-ABL transcripts after transplantation had a predictive value on relapse occurrence. Finally, donor lymphocyte infusions were successfully used to treat some relapses. The graft-versus-leukemia effect of HSCT in Ph-positive ALL appears to be supported by (1) the lack of prognostic significance of pretransplant BCR-ABL transcript detection, (2) the efficacy of donor lymphocyte infusions in cases of relapse, and (3) the role of GvHD as protecting against relapse.


Assuntos
Efeito Enxerto vs Leucemia/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/imunologia , Doença Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/epidemiologia , Sociedades Médicas , Transplante de Células-Tronco/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Resultado do Tratamento
11.
Br J Haematol ; 116(1): 193-201, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11841417

RESUMO

The timing of transplantation in chronic myeloid leukaemia is still debated and previous treatment with interferon (IFN) alpha has been reported to be deleterious. We have analysed the outcome of 438 allogeneic transplants performed between 1984 and 1995 and reported to the Société Française de Greffe de Moelle (SFGM) registry. One hundred and two patients (group I) received IFN for more than 6 weeks (median = 9 months) before transplant. Their outcome was compared with 336 other patients (group II) not pretreated with IFN. There were no significant differences between the groups for engraftment and chronic graft-versus-host disease (GVHD) incidence. However, other significant differences included the incidence of acute GVHD > or = 2 at 3 months which was higher in group I (65 +/- 10%) than in group II (38 +/- 5%; P = 0.01). Moreover, disease-free survival (DFS) and overall survival (OS) at 5 years were significantly shorter for group I than for group II (33 +/- 10% vs. 41 +/- 6%; P = 0.005)(95% CI) and (41 +/- 10% vs. 55 +/- 6%; P = 0.002)(95% CI) respectively. After adjustment for patient and transplant covariables in a multivariate analysis, prior IFN was not found to adversely affect transplant outcome.


Assuntos
Transplante de Medula Óssea , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Distribuição de Qui-Quadrado , Criança , Terapia Combinada , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento
12.
Br J Haematol ; 112(4): 900-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11298584

RESUMO

The epidemiology and clinical outcome of acute myeloid leukaemia in human immunodeficiency virus (HIV)-infected adults is poorly documented. We retrospectively surveyed all French haematology centres for adult acute myeloid leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found to be HIV-seropositive before or at the time of AML diagnosis. Medical charts were reviewed to determine the stage of HIV infection, the characteristics of AML and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three women) were reported by 12 haematology units. Based on assumptions on the size, age and sex distribution of the HIV-infected population in France, the estimated risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the general population (standardized incidence ratio = 2.05; 95% confidence interval, 1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to the authors and were included in the clinical analysis. At AML diagnosis, the median CD4+ cell count was 275 x 106/l and nine patients had acquired immune deficiency syndrome (AIDS). Fifteen patients were scheduled for remission-induction therapy of AML. No deaths were related to AML treatment. Complete remission was obtained in 11 out of 15 patients. Three patients were long-term survivors: two remain alive in complete remission at 8 years and 9 years, respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200 x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P = 0.004). Like many other malignancies, the incidence of AML appears to be increased in HIV-infected patients. Our results show a twofold higher incidence, although this needs to be confirmed in a specifically designed prospective epidemiological study. Such patients, especially those with CD4+ cell counts above 200 x 106/l at AML diagnosis, should receive remission-induction therapy, which can confer long-term survival.


Assuntos
Infecções por HIV/complicações , Leucemia Mieloide/complicações , Doença Aguda , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Contagem de Linfócito CD4 , Intervalo Livre de Doença , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Humanos , Incidência , Leucemia Mieloide/epidemiologia , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Risco , Análise de Sobrevida
13.
Br J Haematol ; 111(1): 292-302, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11091216

RESUMO

In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary ([n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age < 34 years at transplant, an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant.


Assuntos
Rejeição de Enxerto/cirurgia , Transplante de Células-Tronco Hematopoéticas , Leucemia/cirurgia , Adolescente , Adulto , Anemia Aplástica/cirurgia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Imunossupressores/uso terapêutico , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Reoperação , Estudos Retrospectivos , Estatísticas não Paramétricas , Transplante Homólogo , Resultado do Tratamento
14.
Br J Haematol ; 108(3): 595-601, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10759719

RESUMO

We performed a survey from 122 centres of the European Group of Blood and Marrow Transplantation (EBMT) concerning peripheral blood stem cell (PBSC) mobilization after fludarabine treatment of patients with chronic lymphocytic leukaemia (CLL). A total of 101 leucaphereses from 29 patients was performed. The median cell numbers collected were: CD34+ cells, 2.2 x 106/kg (0.1-15.3); granulocyte-macrophage colony-forming units (GM-CFU), 4.29 x 104/kg (0.4-177); and mononuclear cells, 6.4 x 108/kg (1.3-63). In univariate and multivariate analyses, the numbers of cells collected were not significantly influenced by the nature of mobilizing regimen and there was a trend towards the collection of a higher number of CD34+ cells from patients who received fludarabine only before mobilization. There was a significant correlation between the median number of CD34+ cells collected and the number of courses of fludarabine (higher CD34+ cell numbers were related to more than six courses) and the interval between the last dose of fludarabine and the start of mobilizing therapy (higher CD34+ cell numbers were related to a delay > or = 2 months). Sixteen patients have subsequently undergone autologous transplantation and showed rapid engraftment. In conclusion, the results reported favour early stem cell mobilization in CLL patients who are in remission after first-line therapy. However, attention should be given to the timing of mobilization with respect to the time since the last dose of fludarabine.


Assuntos
Antineoplásicos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Linfocítica Crônica de Células B/terapia , Vidarabina/análogos & derivados , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Vidarabina/uso terapêutico
15.
J Clin Oncol ; 18(5): 963-71, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10694545

RESUMO

PURPOSE: To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease. RESULTS: With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome. CONCLUSION: BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.


Assuntos
Transplante de Medula Óssea , Leucemia Megacarioblástica Aguda/terapia , Síndromes Mielodisplásicas/terapia , Segunda Neoplasia Primária/terapia , Transplante Homólogo , Adolescente , Adulto , Feminino , França , Humanos , Leucemia Megacarioblástica Aguda/etiologia , Leucemia Megacarioblástica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/mortalidade , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Análise de Sobrevida
16.
Br J Haematol ; 108(2): 400-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10691873

RESUMO

Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Doença Aguda , Adolescente , Adulto , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Transplante Homólogo
17.
Bone Marrow Transplant ; 26(11): 1157-63, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11149725

RESUMO

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
18.
Eur J Cancer ; 33(14): 2368-75, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9616283

RESUMO

This study investigates the role of high-dose chemotherapy with haematopoietic stem cell rescue as consolidation treatment in high-risk retinoblastoma (extraocular disease at diagnosis or relapse or invasion of cut end of optic nerve). 25 patients received high-dose chemotherapy including carboplatin (250 mg/m2/day from day 1 to day 5 for the 6 first patients and 350 mg/m2/day from day 1 to day 5 for the other patients), etoposide (350 mg/m2/day from day 1 to day 5) and cyclophosphamide (1.6 g/m2/day from day 2 to day 5) (CARBOPEC) followed by autologous haematopoietic stem cell rescue. 19 patients received this drug combination for chemosensitive extraocular relapse. The other 6 patients with histological high-risk factors were given this treatment as consolidation after enucleation and conventional chemotherapy. The three year disease-free survival was 67.1%. In 7 of the 9 relapsing patients, the first site of relapse was the central nervous system. All patients with central nervous system disease died except one. The main toxicity was haematological and digestive (mucositis and diarrhoea). 2 of the 13 evaluable patients had grade III and IV ototoxicity. One patient experienced an acute grade I reversible cardiotoxicity. The CARBOPEC regimen seems to be a promising therapeutic strategy in patients with high-risk retinoblastoma, especially those with bone and/or bone marrow involvement. This treatment did not improve the outcome of patients with central nervous system disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Nefropatias/induzido quimicamente , Masculino , Neutropenia/induzido quimicamente , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico
19.
Nouv Rev Fr Hematol (1978) ; 37(6): 321-5, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8907626

RESUMO

Autologous stem cell transplantation has increased in France over the last five years, mainly due to a marked increase in the number of autologous peripheral blood progenitor cell (PBPC) transplants, which represented about 66% of autologous transplants performed in 1994. This increase is related to the more rapid engraftment observed after PBPC transplantation than after bone marrow transplantation (BMT). The rate of haematopoietic recovery is significantly influenced by the dose of CFU-GM infused, by use of haematopoietic growth factors for mobilization and to a lesser extent after transplantation and by types of conditioning regimens. However, the outcome of patients does not seem to differ following PBPC as compared to bone marrow transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias/terapia , Contagem de Células Sanguíneas , Ensaios Clínicos como Assunto , França , Substâncias de Crescimento/uso terapêutico , Humanos , Neoplasias/mortalidade , Taxa de Sobrevida , Transplante Autólogo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...