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1.
Br J Haematol ; 201(6): 1153-1158, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36974355

RESUMO

Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two-year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines.


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Sociedades Médicas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos
2.
Bone Marrow Transplant ; 52(10): 1428-1435, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28650455

RESUMO

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/imunologia , Recuperação de Função Fisiológica/imunologia , Sistema de Registros , Condicionamento Pré-Transplante , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
3.
Bone Marrow Transplant ; 50(8): 1063-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26030052

RESUMO

In recipients of allogeneic hematopoietic stem cell transplantation with AML in CR1, reduced intensity (RIC) conditioning regimens are usually given to older patients and myeloablative regimens (MAC) to younger patients. We analyzed whether in middle-aged patients aged 40-60 years, MAC was superior to RIC in cytogenetically higher risk AML. Among 2974 patients, 1638 had MAC and 1336 RIC transplants. Cytogenetics were high risk in 508, intermediate risk in 2297 and low risk in 169. Overall survival (OS) was higher in patients with RIC with low-risk cytogenetics but not in the intermediate- or poor-risk AML. Relapse incidence was lower with MAC in poor- and intermediate-risk AML. Nonrelapse mortality (NRM) was higher in MAC in all cytogenetic risk groups. Multivariate analysis confirmed a significant leukemia-free survival and OS advantage for RIC in low risk but no advantage of MAC in intermediate- and poor-risk leukemia. In patients aged 40-60 years, MAC has no advantage over RIC. We confirm lower relapse but higher NRM risks with MAC. MAC is not superior in patients with higher risk cytogenetics, but is inferior to RIC in the small cohort of AML patients with low-risk cytogenetics.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
4.
J Geriatr Oncol ; 6(5): 346-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26116168

RESUMO

INTRODUCTION: Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. RESULTS: The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×109/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. CONCLUSION: In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Sociedades Médicas , Idoso , Idoso de 80 Anos ou mais , Transplante de Medula Óssea , Terapia Baseada em Transplante de Células e Tecidos , Intervalo Livre de Doença , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Linfoma não Hodgkin/epidemiologia , Masculino , Prevalência , Estudos Retrospectivos , Taxa de Sobrevida/tendências
5.
Bone Marrow Transplant ; 49(6): 756-60, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24614840

RESUMO

Progression of Philadelphia-negative myeloproliferative (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) to acute myeloid leukemia (AML) is an adverse event in the course of the disease. Although allogeneic hematopoietic SCT (allo-SCT) is considered as the only curative therapy, few data exist on the outcome of patients with Philadelphia-negative MPN or MDS/MPN in blast phase who received an allo-SCT. Sixty patients were included in this retrospective study. AML was secondary to an MPN in 43 cases, whereas AML evolved from an MDS/MPN in 17 cases. Patients received allo-SCT in CR or advanced disease in 26 cases and 34 cases, respectively. With a median follow-up of 31 months (range, 25-44), OS and leukemia-free survival (LFS) were, respectively, 18% and 9% at 3 years. CR at transplant was associated with an improved LFS in univariate and multivariate analysis. The 3-year LFS was 18% for patients undergoing allo-SCT in CR versus 3% in advanced disease (P=0.008). Absence of thrombosis and an intermediate or favorable AML karyotype were associated with an improved outcome for patients who received allo-SCT in CR. New strategies are needed to improve the outcome of patients with MPN-MDS/MPN in blast phase.


Assuntos
Crise Blástica/terapia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Doenças Mieloproliferativas-Mielodisplásicas/patologia , Doenças Mieloproliferativas-Mielodisplásicas/terapia , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , França , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Bone Marrow Transplant ; 49(3): 361-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24292522

RESUMO

Previous data suggested that allo-SCT might be an effective therapy in the setting of chemo-refractory/relapsed diseases because of the potent long-term immune-mediated tumor control. This retrospective study aimed to analyze the outcome of adult patients who received allo-SCT in a chemo-refractory/relapsed status. The series included 840 patients with active or progressive disease at the time of transplant. Median age was 50 years. With a median follow-up of 40 months, 3-year OS, disease-free survival (DFS), and non-relapse mortality rates were 29±2, 23±2, and 30±2%, respectively. At the last follow-up, 252 patients (30%) were still alive (of whom 201 were in CR (24%). In a Cox multivariate analysis, the use of a reduced-intensity conditioning (RIC) before allo-SCT and use of an HLA-identical sibling donor remained independently associated with a better OS (hazard ratio (HR)=0.82; 95% confidence interval (CI), 0.69-0.98, P=0.03; and HR=0.79; 95% CI, 0.66-0.93, P=0.006, respectively). Also, a diagnosis of myelodysplastic syndrome/myeloproliferative disorder, Hodgkin lymphoma and non-Hodgkin lymphoma compared with acute leukemia had a favorable impact on OS (HR=0.55; 95% CI, 0.45-0.68, P<0.0001; HR=0.49; 95% CI, 0.31-0.75, P=0.001; and HR=0.47; 95% CI, 0.35-0.63, P<0.0001, respectively). In conclusion, this study suggests that allo-SCT may be of benefit in some subgroups of patients with active or progressive hematological malignancies at the time of allo-SCT.


Assuntos
Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco , Transplante Homólogo , Adolescente , Adulto , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , França , Antígenos HLA/química , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/mortalidade , Transtornos Mieloproliferativos/terapia , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Sociedades Médicas , Resultado do Tratamento , Adulto Jovem
7.
Pathol Biol (Paris) ; 61(4): 155-7, 2013 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24011960

RESUMO

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Seleção do Doador/normas , Infecções por Vírus Epstein-Barr/diagnóstico , Transplante de Células-Tronco Hematopoéticas/normas , Achados Incidentais , Sífilis/diagnóstico , Toxoplasmose/diagnóstico , Doadores de Sangue , Consenso , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Vírus Epstein-Barr/sangue , França , Conhecimentos, Atitudes e Prática em Saúde , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunoglobulina M/sangue , Sífilis/sangue , Sífilis/imunologia , Toxoplasma/isolamento & purificação , Toxoplasmose/sangue , Transplante Homólogo
8.
Pathol Biol (Paris) ; 61(4): 158-9, 2013 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24011965

RESUMO

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.


Assuntos
Doadores de Sangue , Seleção do Doador/normas , Conhecimentos, Atitudes e Prática em Saúde , Transplante de Células-Tronco Hematopoéticas/normas , Achados Incidentais , Paraproteinemias/diagnóstico , Testes de Gravidez , Consenso , Feminino , Idade Gestacional , Humanos , Paraproteinemias/sangue , Gravidez/sangue , Complicações na Gravidez/sangue , Complicações na Gravidez/prevenção & controle
11.
Transfus Clin Biol ; 17(4): 265-8, 2010 Oct.
Artigo em Francês | MEDLINE | ID: mdl-20961787

RESUMO

A 56 year-old, multiparous woman suffering from a myeloproliferative syndrome, who had received multiple red blood cell and platelet transfusions, was the recipient of an allograft of peripheral blood stem cells derived from her HLA-A, B, DR, DQ and DP and ABO identical sister, following myeloablative conditioning. The persistence of severe, isolated thrombopenia resistant to platelet transfusions led to the discovery of anti-HLA class I allo-immunisation. As HLA compatible platelet transfusions did not result in satisfactory platelet increments, we then discovered the simultaneous presence of anti-HPA-1a allo-immunisation. Genotyping of the HPA-1 systems of the patient (HPA-1B/B) and her sister (HPA-1A/B) enabled us to elucidate the mechanism underlying the persistent thrombopenia and the inefficacy of transfusion. In fact, only transfusion of HPA-1B/B platelets (HLA compatible or incompatible) proved to be efficacious. To reduce the level of anti-HPA-1a antibodies, we performed plasmapheresis sessions and used an anti-CD20 monoclonal antibody. It was only on achieving total haematopoietic chimerism, through rapid interruption of the immunosuppression, that we obtained spontaneous normalisation of the platelet count. The present case emphasises the necessity, before undertaking any allograft of haematopoietic stem cells - even if the latter come from a strictly HLA identical member of the family - of performing a search for eventual anti-HPA allo-immunisation.


Assuntos
Antígenos de Plaquetas Humanas/imunologia , Transplante de Medula Óssea/efeitos adversos , Trombocitopenia/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença
12.
Bone Marrow Transplant ; 36(10): 901-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16151421

RESUMO

The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.


Assuntos
Eritropoetina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Hemoglobinas/efeitos dos fármacos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Eritropoese/efeitos dos fármacos , Eritropoetina/toxicidade , Feminino , Neoplasias Hematológicas/terapia , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Projetos Piloto , Proteínas Recombinantes , Transplante Homólogo
13.
Eur J Haematol ; 74(2): 169-71, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15654910

RESUMO

T-cell lymphoma is an aggressive lymphoma that cannot be cured despite aggressive therapy, including autologous stem cell transplantation. Thalidomide is an immunomodulatory drug with numerous properties that has proven effective in relapsed multiple myeloma and, to a lesser extent, in other hematologic diseases. We report three cases of relapsed refractory T-cell lymphoma treated with thalidomide with a good tumor response.


Assuntos
Imunossupressores/administração & dosagem , Linfoma de Células T/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Talidomida/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico
14.
Bone Marrow Transplant ; 34(6): 527-30, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15286687

RESUMO

The use of reduced intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) can result in a significant decrease in early procedure-related toxicity in patients not eligible for standard myeloablative regimens. However, acute graft-versus-host disease (aGVHD) remains a matter of concern after RIC allo-SCT, and its incidence might be expected to be higher in elderly and high-risk patients. This report investigated mycophenolate mofetil (MMF) and cyclosporin A (CsA) combination (n=14) in comparison to CsA alone (n=20) for GVHD prophylaxis in cancer patients aged over 50 years (27 haematological malignancies and seven solid tumours) receiving an HLA-identical sibling antithymocyte-globulin (ATG)-based RIC allo-SCT. Baseline demographic characteristics and risk factors for aGVHD were comparable between both groups. Although MMF administration was not associated with any significant toxicity, the cumulative incidence of any form of GVHD was comparable between both groups (cumulative incidence of grade II-IV aGVHD, 50% (95% CI, 28-72%) for CsA alone, as compared to 64% (95% CI, 39-89%) to CsA and MMF, P=NS), suggesting that adjunction of MMF to CsA is feasible, but does not translate towards a significant reduction of aGVHD, at least in the context ATG-based RIC allo-SCT.


Assuntos
Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Transplante de Células-Tronco , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Quimioterapia Combinada , Teste de Histocompatibilidade , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Irmãos , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/imunologia
15.
Bone Marrow Transplant ; 34(1): 77-84, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15133485

RESUMO

In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.


Assuntos
Soro Antilinfocitário/administração & dosagem , Efeito Enxerto vs Tumor/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Incidência , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem
16.
Transfusion ; 44(4): 501-8, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15043564

RESUMO

BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n=64) or a myeloablative conditioning regimens (MAC; n=46). Patients received marrow (n=64) or PBPCs (n=46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p=0.0005) and graft source (PBPC vs. marrow; p<0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p=0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p<0.0001) and the dose of ATG (p=0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.


Assuntos
Antineoplásicos/farmacologia , Transfusão de Eritrócitos/estatística & dados numéricos , Eritropoese/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemoglobinas/análise , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Valor Preditivo dos Testes , Prognóstico , Transplante Homólogo
17.
Bone Marrow Transplant ; 33(8): 839-46, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14767500

RESUMO

Cytomegalovirus (CMV) represents a major cause of morbidity after allogeneic stem cell transplantation (allo-SCT). Using interferon-gamma-enzyme-linked immunospot (ELISPOT) assay and HLA-peptide tetramers, we analysed 54 patients who received a reduced-intensity conditioning regimen, including fludarabine, busulphan and antithymocyte globulin (ATG), with the aim of defining essential elements of protective immunity to CMV. The cumulative incidence of CMV positive antigenaemia was 37% occurring at a median of 43 days (range, 7-104) after allo-SCT. In univariate analysis, conditioning regimen (ATG dose) and graft characteristics (graft source and CD3+ T-cell dose) significantly influenced CMV-specific immune recovery. A significant correlation (P=0.000002) was found between CMV-specific T cells detected by IFN-gamma ELISPOT assay and pp65-specific CD8+ T-cell frequency quantified by tetramers. CMV-specific CD8+ T cells presented a phenotype of effector cells (perforin and 2B4 positive). In multivariate analysis, bone marrow (BM) as a graft source was the only variable associated with an increased risk of CMV positive antigenaemia (P=0.0001) in line with the ELISPOT assay showing a higher frequency of functional CMV-specific effectors within peripheral blood stem cell grafts as compared to BM. Thus, early monitoring of CMV-specific immune recovery using sensitive new tools might prove useful for patient management after allo-SCT.


Assuntos
Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Adulto , Antígenos Virais/sangue , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Feminino , Antígenos HLA , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Irmãos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
18.
Ann Hematol ; 83(6): 390-3, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-14666380

RESUMO

A 57-year-old man with acute myeloid leukemia (AML) French-American-British (FAB) 4 developed disseminated invasive cerebral and pulmonary aspergillosis during postinduction aplasia. According to international consensus, infection was categorized as probable (two host factors: deep neutropenia for >10 days and refractory fever for >96 h; major clinical criteria of lower respiratory tract and CNS invasive fungal infection; positive results for galactomannan antigen in three blood samples). After the failure of standard amphotericin-based therapy, the spectacular regression of multifocal brain and lung lesions was rapidly achieved under a caspofungin acetate/voriconazole combination. Further permanent caspofungin maintenance with voriconazole added during aplasia periods permitted two consolidation courses and autograft-based intensification without any delay.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose/tratamento farmacológico , Leucemia Mielomonocítica Aguda/microbiologia , Peptídeos Cíclicos , Peptídeos/administração & dosagem , Pirimidinas/administração & dosagem , Triazóis/administração & dosagem , Aspergilose/diagnóstico por imagem , Caspofungina , Quimioterapia Combinada , Equinocandinas , Humanos , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento , Voriconazol
20.
Leukemia ; 17(11): 2168-77, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12931226

RESUMO

In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.


Assuntos
Infecções Bacterianas/etiologia , Irmãos , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/efeitos adversos , Viroses/etiologia , Sistema ABO de Grupos Sanguíneos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Infecções Bacterianas/epidemiologia , Incompatibilidade de Grupos Sanguíneos , Infecções por Citomegalovirus/prevenção & controle , Feminino , Ganciclovir/uso terapêutico , Rejeição de Enxerto/epidemiologia , Doença Enxerto-Hospedeiro/epidemiologia , Teste de Histocompatibilidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/mortalidade , Análise de Sobrevida , Fatores de Tempo , Viroses/epidemiologia
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