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1.
Artigo em Inglês | MEDLINE | ID: mdl-31421238

RESUMO

Post-transplantation lymphoproliferative disease (PTLD) is a serious complication associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although anti-CD-20 therapy is now used as a preemptive strategy for EBV reactivation, PTLD still occurs in some patients. Here we analyzed outcomes and risk factors associated with PTLD transformation in 208 HSCT recipients who were diagnosed with EBV-DNAemia and received at least 1 course of rituximab. The median patient age was 42.52 years (range, 8.35 to 74.77 years), and the median duration of follow-up was 47.33 months (range, 3.18 to 126.20 months). The 2-year overall survival of the entire cohort was 62.8 (95% confidence interval [CI], 56.4 to 69.9), and the 2-year cumulative incidence function of PTLD was 6.3% (95% CI, 3.5% to 10.1%), for a median follow-up of patients diagnosed with PTLD of 37.85 months. Multivariable analysis identified 4 risk factors associated with PTLD: HSCT from an unrelated donor, recipient HLA-DRB1*11:01, fever at diagnosis of EBV infection, and donor-recipient sex-mismatched HSCT. The presence of more than 2 of these risk factors was associated with an increased risk of developing PTLD. This retrospective study identifies risk factors associated with PTLD in EBV-infected patients after HSCT and defines patient subgroups that may benefit from intensified preemptive strategies.

3.
Haematologica ; 103(8): 1278-1287, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29724903

RESUMO

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.

6.
Haematologica ; 103(2): 212-220, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29170252

RESUMO

Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naïve patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×109/L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naïve and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.

8.
Haematologica ; 101(6): 764-72, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27036159

RESUMO

We previously reported that bone marrow grafts from matched sibling donors resulted in best graft-versus-host disease-free, relapse-free survival at 1-year post allogeneic hematopoietic cell transplantation. However, pediatric patients comprised the majority of bone marrow graft recipients in that study. To better define this outcome in adults and pediatric patients at 1- and 2-years post- allogeneic hematopoietic cell transplantation, we pooled data from the University of Minnesota and the Hôpital Saint-Louis in Paris, France (n=1901). Graft-versus-host disease-free, relapse-free survival was defined as the absence of grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease (requiring systemic therapy or extensive stage), relapse and death. In adults, bone marrow from matched sibling donors (n=123) had best graft-versus-host disease-free, relapse-free survival at 1- and 2-years, compared with peripheral blood stem cell from matched sibling donors (n=540) or other graft/donor types. In multivariate analysis, peripheral blood stem cells from matched sibling donors resulted in a 50% increased risk of events contributing to graft-versus-host disease-free, relapse-free survival at 1- and 2-years than bone marrow from matched sibling donors. With limited numbers of peripheral blood stem cell grafts in pediatric patients (n=12), graft-versus-host disease-free, relapse-free survival did not differ between bone marrow and peripheral blood stem cell graft from any donor. While not all patients have a matched sibling donor, graft-versus-host disease-free, relapse-free survival may be improved by the preferential use of bone marrow for adults with malignant diseases. Alternatively, novel graft-versus-host disease prophylaxis regimens are needed to substantially impact graft-versus-host disease-free, relapse-free survival with the use of peripheral blood stem cell.


Assuntos
Intervalo Livre de Doença , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , França , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas , Humanos , Incidência , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo , Transplante Homólogo , Adulto Jovem
10.
Bull Cancer ; 103 Suppl 1: S164-S174, 2016 Nov.
Artigo em Francês | MEDLINE | ID: mdl-28057181

RESUMO

IMMUNOTHERAPY AND ALLOGENEIC STEM CELLS TRANSPLANTATION: Allogeneic stem cell transplantations represent perfect example of immunotherapy. Its positive aspects are due to the graft versus tumor effect. Unfortunately, this therapeutic advantage is usually associated with graft versus host effects. While the mechanism of these two graft reactions remain unclear, this is possible to modulate these immunologic effects. The type of conditioning regimen, the source of donor and the use of donor cells after the transplantation may influence the toxicity and the tumor response, leading to a better optimization of the procedure. This paper is presenting all the parameters which may contribute to improve allogeneic stem cell transplantations.


Assuntos
Efeito Enxerto vs Tumor/imunologia , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Imunoterapia/métodos , Condicionamento Pré-Transplante , Reação Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histocompatibilidade/genética , Histocompatibilidade/imunologia , Humanos , Imunomodulação , Imunoterapia/efeitos adversos , Células Matadoras Naturais/imunologia , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Transplante Homólogo/efeitos adversos
11.
Transplantation ; 99(9): 1953-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25651309

RESUMO

BACKGROUND: Thrombotic microangiopathy (TMA) occurring after allogeneic hematopoietic stem cell transplantation (HSCT) has a devastating prognosis. Response rates to current therapies (mainly plasma exchange) are unsatisfactory. Thrombotic microangiopathy after allogeneic HSCT shares similarities with atypical hemolytic uremic syndrome (aHUS) in the underlying pathomechanisms. Eculizumab has been associated with impressive results in aHUS. MATERIALS AND METHODS: We retrospectively analyzed 12 patients who received Eculizumab in France between 2010 and 2013 for severe post-HSCT TMA. RESULTS: All 12 patients had severe TMA with neurological and/or renal involvement. Fifty-eight percent were refractory to first-line plasma exchange. At the time of TMA diagnosis, infections were present in 50% of the patients and acute graft-versus-host disease in 33%. Patients were treated with Eculizumab according to the aHUS therapeutic scheme. With a median follow-up of 14 months, hematological response and overall survival were 50% and 33%, respectively. Active acute graft-versus-host disease at TMA diagnosis was the only factor associated with worse overall survival (P = 0.009). DISCUSSION: Response rate and overall survival after Eculizumab in our cohort compare favorably with previously published data in TMA after allogeneic HSCT. Prospective trials are warranted to confirm these results. Early initiation of Eculizumab may have a favorable effect on long-term renal function and further contribute to the prolongation of survival.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microangiopatias Trombóticas/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , França , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/mortalidade , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
13.
Biol Blood Marrow Transplant ; 20(8): 1238-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24732781

RESUMO

Viral respiratory infections (VRIs) are frequent after hematopoietic stem cell transplantation and constitute a potential cause of mortality. We analyzed the incidence, risk factors, and prognosis of VRIs in a cohort of transplanted patients. More frequent viruses were human coronavirus and human rhinovirus followed by flu-like viruses and adenovirus. Risk factors for death were lymphocytopenia and high steroid dosage.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Respiratórias/diagnóstico , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/etiologia , Infecções Respiratórias/virologia , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo/mortalidade , Resultado do Tratamento , Adulto Jovem
14.
Transplantation ; 97(7): 725-9, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24598937

RESUMO

BACKGROUND: Neutropenia is common after kidney transplantation and is associated with an increased incidence of infections. Drug toxicities are the main causes of posttransplant neutropenia (PTN), mainly related to immunosuppressive drugs as mycophenolic acid (MPA) and anti-infectious agents, but some PTN remain unexplained. METHODS: Between January 2012 and January 2013, cultures of autologous granulocytic progenitors from bone marrow aspirate were performed in two patients with unexplained severe neutropenia. RESULTS: Both patients' serum inhibited granulocytic differentiation while granulocytic differentiation was normal with the control serum. Similar inhibition of differentiation of granulocytic progenitors from a control marrow was observed with the patients' serum as compared with the control serum. Moreover, in both cases intravenous immunoglobulins allowed full neutrophil count recovery. Other usual etiologies of acquired neutropenia including systemic drug toxicity, infection, and autoimmune disease were excluded. As frequently observed in adult immune neutropenia, granulocyte autoantibodies were absent in both cases. Owing to biological and clinical results, we concluded that an autoimmune mechanism was responsible for neutropenia. The levels of MPA, which is known to interact with tacrolimus, were not measured in our patients. However, the persistence of neutropenia more than 70 days after withdrawal of MPA did not support this hypothesis. CONCLUSION: Autoimmune neutropenia should be considered in kidney transplant recipients in case of persistent unexplained neutropenia as it allows effective treatment and avoids the withdrawal of important immunosuppressive and anti-infectious treatments.


Assuntos
Doenças Autoimunes/complicações , Transplante de Rim/efeitos adversos , Neutropenia/etiologia , Adulto , Feminino , Humanos , Masculino
15.
J Clin Microbiol ; 51(12): 4186-92, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24108617

RESUMO

Hematopoietic stem cell transplant patients are highly susceptible to viral infections. Follow-up after transplantation includes weekly screening using single, virus-specific real-time PCR tests, mainly for viruses in the families Herpesviridae and Adenoviridae that contribute to a high morbidity, especially in pediatric populations. The Abbott PLEX-ID platform combines broad-range PCR with electrospray ionization mass spectrometry to enable the simultaneous detection of multiple pathogens in a single assay. The Viral IC Spectrum assay detects human adenoviruses, viruses from the family Herpesviridae (herpes simplex virus 1 [HSV-1], HSV-2, cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], and human herpesvirus 8 [HHV-8]), human enterovirus, polyomaviruses (BK and JC), and parvovirus B19. We evaluated the performance of the Viral IC Spectrum assay with samples from 16 adult and 36 pediatric stem cell transplant patients. The sensitivity of the Viral IC Spectrum assay compared to real-time PCR quantification using the adenovirus Rgene kit for the detection of adenovirus was 96.7% from plasma samples (n = 92) and 78% from stool samples (n = 100). No adenovirus was detected in samples from noninfected patients (n = 30). PLEX-ID species identification was perfectly concordant with species-specific real-time PCR assays. In plasma and stool samples, the level of amplified products measured by PLEX-ID and the quantity in copies/ml (r = 0.82 and 0.78, respectively) were correlated up to 6 log10 copies/ml. In 67.4% of adenovirus-positive plasma samples, at least one other viral infection was detected; these included BK virus (n = 41), CMV (n = 30), EBV (n = 26), JC virus (n = 9), and HSV-1 (n = 6). The results of this study suggest that the Viral IC Spectrum assay performed on the PLEX-ID platform is reliable for adenovirus infection diagnosis in immunocompromised patients.


Assuntos
Infecções por Adenoviridae/diagnóstico , Adenovírus Humanos/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Transplante , Infecções por Adenoviridae/virologia , Adenovírus Humanos/classificação , Adenovírus Humanos/genética , Adulto , Criança , Pré-Escolar , Fezes/virologia , Genótipo , Humanos , Plasma/virologia
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